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| J Cell Sci, 2002 Jul 1, 115(Pt 13), 2791 - 800 Ca2+-induced changes in SNAREs and synaptotagmin I correlate with triggered exocytosis from chromaffin cells: insights gleaned into the signal transduction using trypsin and botulinum toxins; Lawrence GW et al.; Ca2+-triggered catecholamine exocytosis from chromaffin cells involves SNAP-25, synaptobrevin and syntaxin (known as SNAREs) . Synaptotagmin I has been implicated as the Ca2+-sensor because it binds Ca2+, and this enhances its binding to syntaxin, SNAP-25 and phospholipids in vitro . However, most of these interactions are only mediated by {Ca2+}i two orders of magnitude higher than that needed to elicit secretion . Thus, the Ca2+ sensitivities of synaptotagmin I and the other SNAREs were quantified in situ . Secretion elicited from permeabilised cells by microM Ca2+ was accompanied, with almost identical Ca2+ dependencies, by changes in synaptotagmin I, SNAP-25, syntaxin and synaptobrevin that rendered them less susceptible to trypsin . The majority of the trypsin-resistant SNAREs were not associated with SDS-resistant complexes . None of these proteins acquired trypsin resistance in cells rendered incompetent for exocytosis by run-down . Removal of nine C-terminal residues from SNAP-25 by botulinum toxin A reduced both exocytosis and the SNAREs' acquisition of trypsin resistance but did not alter the Ca2+ sensitivity, except for synaptotagmin I . Even after synaptobrevin had been cleaved by botulinum toxin B, all the other proteins still responded to Ca2+ . These data support a model whereby Ca2+ is sensed, probably by synaptotagmin I, and the signal passed to syntaxin and SNAP-25 before they interact with synaptobrevin. Toxicon, 2002 Jul, 40(7), 923 - 8 Botulinum neurotoxin serotypes A and B preparations have different safety margins in preclinical models of muscle weakening efficacy and systemic safety; Roger Aoki K; This preclinical study compared the muscle weakening efficacy, duration, and safety margin of the recently approved botulinum toxin type B (BTX-B; Myobloc/Neurobloc) to botulinum toxin type A (BTX-A; BOTOX((R))) . Mice received a single hind limb intramuscular injection of BTX-B (1-150U/kg) or BTX-A (1-120U/kg) . An observer who was masked to treatment assessed the magnitude and duration of muscle weakening efficacy on a 0-4 scale using the digit abduction scoring assay . Safety margins were determined as the ratio of the IM median lethal dose to the IM dose that produced half-maximal muscle weakness in the DAS . BTX-A produced muscle weakness at lower doses than BTX-B (IM ED(50): 6.2+/-0.6 vs . 20.8+/-1.4U/kg, respectively) (p<0.0001) . BTX-A at 29U/kg and BTX-B at 67U/kg produced comparable peak DAS scores of approximately 4 indicating maximal muscle weakness . At these doses, the duration of BTX-A was longer, with a return to baseline by day 36 compared to a return to baseline by day 14 with BTX-B . The mean dose that was lethal in 50% of mice was lower for BTX-A than BTX-B (81.4+/-3.5 vs . 104.6+/-1.9U/kg, respectively) (p<0.001) and the safety margin was higher (13.9+/-1.7 vs . 5.4+/-0.3, respectively (p<0.001) . These results indicate that the BTX-A:BTX-B dose ratio for muscle weakening efficacy is different from the ratio for systemic effects following IM injections and suggest that no single dose ratio is adequate to compare these preparations . The in vivo differences found are consistent with the different clinical profiles reported for these two products. Pharmacol Toxicol, 2002 Apr, 90(4), 199 - 202 The mechanism underlying the protective effect of the thearubigin fraction of black tea (Camellia sinensis) extract against the neuromuscular blocking action of botulinum neurotoxins; Satoh E et al.; The aim of the present study was to elucidate the mechanism of the protective effect of black tea extract, the thearubigin fraction, against the neuromuscular blocking action of botulinum neurotoxin types A, B, and E . The effects of thearubigin fraction extracted from a black tea infusion were examined on the neuromuscular blocking action of botulinum neurotoxin types A, B, and E in mouse phrenic nerve-diaphragm preparations and on the binding of these toxins to rat cerebrocortical synaptosomes . Botulinum neurotoxin type A (1.5 nM), B (6 nM), or E (5 nM) abolished indirect twitches in mouse phrenic nerve-diaphragm preparations within 50, 90, 90 min., respectively . Thearubigin fraction mixed with each toxin blocked the inhibitory effect of the toxins . The specific binding of {125I}botulinum neurotoxin type A, B, or E to rat cerebrocortical synaptosomes was inhibited by mixing iodinated toxin with thearubigin fraction . The elution profile of {125I}botulinum neurotoxin type A, B, or E on Sephadex G-50 column chromatography was different from that of toxin mixed with thearubigin fraction . These findings indicate that thearubigin fraction protects against the neuromuscular blocking action of botulinum neurotoxin types A, B, and E by binding with the toxins. Otolaryngol Head Neck Surg, 2002 May, 126(5), 459 - 67 Botulinum toxin type B (MyoBloc) in the management of hyperkinetic facial lines; Ramirez AL et al.; OBJECTIVE: Our goal was to evaluate the safety and efficacy of botulinum toxin type B (BTX-B) in the management of hyperfunctional facial lines . STUDY DESIGN AND SETTING: Twenty-four patients from an academic faculty practice were treated with 400 to 800 units BTX-B in the corrugator, orbicularis oculi, or frontalis . Patients were evaluated with the Wrinkle Improvement Score (WIS) and Rated Numeric Kinetic Line Scale (RNKLS) and questioned about side effects and pain . Evaluations were made at 1, 2, 4, 8, and 12 weeks . RESULTS: Onset of effect was within 72 hours . WIS and RNKLS for all sites were statistically better after treatment, with the effect lasting 8 weeks . In general, patients noted a moderate improvement (grade 2) on WIS and a 2-point improvement on RNKLS . Injection was more painful than that of BTX-A . There were no complications . CONCLUSION: BTX-B is a safe and effective technique to eliminate wrinkles . Further studies are needed to elucidate dosage and duration . SIGNIFICANCE: BTX-B is stable for prolonged periods of time, requires no preparation before use, and is antigenetically distinct from BTX-A. J Speech Lang Hear Res, 2002 Jun, 45(3), 469 - 81 Botox treatment in adductor spasmodic dysphonia: a meta-analysis; Boutsen F et al.; Over the years many studies have been conducted to document the treatment effects of Botulinum toxin type A in adductor spasmodic dysphonia . The results of these studies have led to the view that overall Botulinum toxin treatment is moderately effective . This study reviews efficacy research qualitatively and quantitatively to determine the extent to which this conclusion is fully supported by the data . Although the data indicate moderate overall improvement as a result of Botulinum toxin treatment, they also suggest significant variation across patients, measurements, and treatment conditions . This result, together with methodological limitations and lack of standardization in BT efficacy research, justifies caution when making inferences regarding BT treatment benefit in adductor spasmodic dysphonia. Arq Neuropsiquiatr, 2002 Jun, 60(2-A), 288 - 9 Hemimasticatory spasm treated with botulinum toxin: case report; Teive HA et al.; We describe a female patient with hemimasticatory spasm, a rare movement disorder due to dysfunction of the motor trigeminal nerve of unknown origin . This patient had an excellent response to botulinum toxin therapy. Neuroepidemiology, 2002 Jul-Aug, 21(4), 202 - 6 Service-based survey of dystonia in munich; Castelon Konkiewitz E et al.; We performed a service-based epidemiological study of dystonia in Munich, Germany . Due to favourable referral and treatment patterns in the Munich area, we could provide confident data from dystonia patients seeking botulinum toxin treatment . A total of 230 patients were ascertained, of whom 188 had primary dystonia . Point prevalence ratios were estimated to be 10.1 (95% confidence interval 8.4-11.9) per 100,000 for focal and 0.3 (0.0-0.6) for generalised primary dystonia . The most common focal primary dystonias were cervical dystonia with 5.4 (4.2-6.7) and essential blepharospasm with 3.1 (2.1-4.1) per 100,000 followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4-1.5) per 100,000 . J Neurochem, 2002 May, 81(3), 533 - 40 Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture; Yamada H et al.; 5-hydroxytryptamine (5-HT) is a precursor and a putative modulator for melatonin synthesis in mammalian pinealocytes . 5-HT is present in organelles distinct from l-glutamate-containing synaptic-like microvesicles as well as in the cytoplasm of pinealocytes, and is secreted upon stimulation by norepinephrine (NE) to enhance serotonin N-acetyltransferase activity via the 5-HT2 receptor . However, the mechanism underlying the secretion of 5-HT from pinealocytes is unknown . In this study, we show that NE-evoked release of 5-HT is largely dependent on Ca2+ in rat pinealocytes in culture . Omission of Ca2+ from the medium and incubation of pineal cells with EGTA-tetraacetoxymethyl-ester inhibited by 59 and 97% the NE-evoked 5-HT release, respectively . Phenylephrine also triggered the Ca2+-dependent release of 5-HT, which was blocked by phentolamine, an alpha antagonist, but not by propranolol, a beta antagonist . Botulinum neurotoxin type E cleaved 25 kDa synaptosomal-associated protein and inhibited by 50% of the NE-evoked 5-HT release . Bafilomycin A1, an inhibitor of vacuolar H+-ATPase, and reserpine and tetrabenazine, inhibitors of vesicular monoamine transporter, all decreased the storage of vesicular 5-HT followed by inhibition of the NE-evoked 5-HT release . Agents that trigger L-glutamte exocytosis such as acetylcholine did not trigger any Ca2+-dependent 5-HT release . Vice versa neither NE nor phenylephrine caused synaptic-like microvesicle-mediated l-glutamate exocytosis . These results indicated that upon stimulation of a adrenoceptors pinealocytes secrete 5-HT through a Ca2+-dependent exocytotic mechanism, which is distinct from the exocytosis of synaptic-like microvesicles. J Chromatogr A, 2002 Apr 5, 952(1-2), 99 - 110 Initial purification of recombinant botulinum neurotoxin fragments for pharmaceutical production using hydrophobic charge induction chromatography; Weatherly GT et al.; Initial purification of two serotypic variants of recombinant botulinum neurotoxin toxin heavy chain fragment {rBoNT(Hc)}, produced intracellularly in the yeast Pichia pastoris, using hydrophobic charge induction chromatography (HCIC) is reported . HCIC employs a matrix containing a weakly ionizable ligand that binds proteins through hydrophobic interactions at neutral pH and elutes the proteins by charge repulsion at acidic pH . HCIC optimization led to different purification conditions for each of the proteins even though they have 58% sequence similarity . The HCIC resin has a higher affinity for the fragment of serotype A than that of serotype B . The 10% dynamic breakthrough capacity for the serotype A fragment is >12.5 mg per ml of resin and is approximately 3.5 mg or the serotype B fragment per ml of resin . Stable elution conditions are also different for the two serotypes . The serotype A fragment is unstable when citrate is used to elute the product . However the serotype B fragment is stable when eluted with citrate buffer, and it is further purified by a overnight precipitation caused by the citrate buffer . This paper reports the development strategy, dynamic capacity breakthrough curves, resin and separation reproducibility, and preliminary scale-up data . The summation of the data demonstrates that HCIC is a scaleable process step for biopharmaceutical production of rBoNT(Hc) proteins. J Am Acad Dermatol, 2002 Jun, 46(6), 840 - 9 A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines; Carruthers JA et al.; BACKGROUND: Botulinum toxin type A (BTX-A) is widely used for facial esthetics but is incompletely studied . OBJECTIVE: This study was conducted to evaluate the efficacy and safety of BTX-A treatment of glabellar lines . METHODS: Patients with moderate to severe glabellar lines at maximum frown received intramuscular injections of 20 U BTX-A (BOTOX, Allergan, Inc, Irvine, Calif) or placebo into 5 glabellar sites . Patients were followed up for 120 days after injection . Outcome measures were physician rating of glabellar line severity at maximum frown and rest, patient assessment of improvement, and vital sign and adverse event monitoring . RESULTS: Two hundred sixty-four patients were enrolled (BTX-A: 203, placebo: 61) . There was a significantly greater reduction in glabellar line severity with BTX-A than with placebo (all measures, every follow-up visit; P <.022) . The effect was maintained for many patients through day 120 . There was a low occurrence (5.4%) of mostly mild blepharoptosis in the BTX-A group . CONCLUSION: BTX-A injections are safe and effective in reducing the severity of glabellar lines. J Dermatolog Treat, 2002 Jun, 13(2), 91 - 3 Botulinum toxin treatment for a compensatory hyperhidrosis subsequent to an upper thoracic sympathectomy; Huh CH et al.; BACKGROUND: Compensatory hyperhidrosis is the commonest complication of sympathectomy, but there's no known effective treatment . METHODS: Botulinum toxin type A (a total dose of 300 MU, 1.0 MU/cm(2)) was used successfully to treat a 68-year-old male with a 5-year history of compensatory hyperhidrosis of the anterior chest following thoracic sympathectomy for palmar hyperhidrosis . RESULTS: The hyperhidrosis resolved for 8 months without systemic side effects . CONCLUSION: Intracutaneous injection of botulinum toxin is a fast, safe, effective and well-accepted approach for treatment of compensatory hyperhidrosis. Vaccine, 2002 Jun 7, 20(19-20), 2556 - 61 Production and immunogenic efficacy of botulinum tetravalent (A, B, E, F) toxoid; Torii Y et al.; A tetravalent (type A, B, E and F) toxoid was produced and its efficacy and safety were assessed . The toxoid preparation was inoculated from two to five times to 15 healthy adult volunteers participating in botulinum toxin research.The serum samples taken from the toxoid recipients were titrated for the antitoxin potencies by enzyme-linked immunosorbent assay (ELISA) and the neutralization test . The neutralizing and ELISA titers were too low to correlate each other . The mean neutralization titer of four recipients in 9 months after three doses of toxoid was about 0.1IU/ml for each of the four types, whereas, the one receiving five doses possessed a higher titer . Since the amount of the toxin handled in laboratory work is usually not so large, three or more doses of the present toxoid will bestow sufficient immunity on the workers participating in botulinum research . Nevertheless booster injections might be desirable to those at higher risk, handling the toxin of a high concentration. Neurol Neurochir Pol, 2002 Jan-Feb, 36(1), 47 - 56 {Prognostic factors of long-standing improvement in cervical dystonia, treated with botulinum A toxin}; Slawek J et al.; The clinical improvement after injections of botulinum toxin A in patients with idiopathic spasmodic torticollis lasts usually about 3 months . Nevertheless in some patients it exceeds several months . The aim of our study was to assess the frequency of prolonged response (arbitrally established as > 6 months) and to find the possible prognostic factors of such longer effect . In the group of 43 patients (F30, M13), average age 43.9 (19-72) years, we observed prolonged effect in 13 (30.2%) . In 5 of them remission was repeated in following sessions (two times in four and four times in one) . The frequency of spontaneous remissions in spasmodic torticollis (12%) is significantly lower than after botulinum toxin, what means that they are triggered by drug injection in our group of patients with prolonged effect . Within the analysed parameters only the lower average age and the average age at the onset of symptoms statistically significantly differ in both groups . The authors suggest the possibility of other mechanisms responsible for prolonged clinical effect after botulinum toxin: e.g . different time of reinnervation (remodelling of synapses) or the modification of natural course (feed-back mechanisms) of spasmodic torticollis in some patients. Neurol Neurochir Pol, 2002 Jan-Feb, 36(1), 33 - 46 {Neurological disorders in post-traumatic algodystrophy of the upper extremity}; Zyluk A et al.; Sensory disturbances (hypoaesthesia in fingertips and tenderness) and movement disorders (tremor, dystonia, muscle spasms, abnormal postures and inability in initiating of movement) were investigated in 80 patients with post-traumatic reflex sympathetic dystrophy (RSD) of the upper extremity . Sensory disturbances were found in 67 patients (84%): most frequently hypoaesthesia in fingertips--in 49, and tenderness of the dorsal aspect of the hand in 24; in six patients both these signs were present simultaneously . Movement disorders were found less frequently: tremor was observed in 12 patients, spasms of the flexor muscles of the forearm and hand in two, postural dystonia in one, and inability initiating of movement in the other one . Sympathetic interruptions reduced movement disturbances in two patients . Dystonia was resistant to various treatment approaches including botulinum toxin injections . Certain hypothesis explaining pathogenic background of motor and sensory disorders in RSD are discussed . The results of this study show that sensory disturbances are frequently observed in RSD, however, they usually disappear after successful treatment of the condition; movement disorders are less frequent, but much more difficult to control . Neurologists are not frequently faced with the problem of neurological disorders after trauma of the limb . Inclusion of RSD in differential diagnosis may improve recognition of the disorder and result in its faster and proper management. Neurol Neurochir Pol, 2002 Jan-Feb, 36(1), 173 - 9 {Laryngeal dystonia--personal experience with botulin toxin treatment}; Domzal TM et al.; Laryngeal dystonia is a focal dystonia occurring more often than it is diagnosed . Adductor type dystonia was described in 5 patients . In 3 cases it manifested itself as blepharospasm, which later developed into Meige's syndrome . The patients were treated with botulinum toxin A injections under EMG control administering 10 i.m . into laryngeal muscles on both sides with good and very good results . There were no serious side effects. Orbit, 1998 Sep, 17(3), 173 - 178 Botulinum toxin as adjunct for refractory compressive optic neuropathy in Graves' disease; Simonsz HJ et al.; An euthyroid patient was referred for compressive optic neuropathy in Graves' disease . Under prednisone therapy the right and left visual acuities were 1.0 and 0.4, with a profound decrease in color vision on the left . Bilateral anterior orbital decompressions were performed . When prednisone was withdrawn postoperatively, the visual acuity of the right eye dropped to 0.32 with bilateral complete failure on the Ishihara color test . A biopsy of the inferior oblique muscle of the left eye confirmed Graves' disease and additional transantral decompression of the right orbital apex was performed . Under intravenous methylprednisolone therapy, the visual acuity dropped postoperatively to 0.2 and 0.4, respectively . 15 U botulinum toxin were given by retrobulbar injection between the inferior and lateral rectus muscles . Four days later the patient called and said that the visual acuity in the right eye had improved tremendously . Two weeks after the injection the visual acuity was 0.7 in both eyes, although prednisone had been reduced to 20 mg by that time . The convergent strabismus had increased but the already severely restricted motility of the right eye had been little affected by the retrobulbar injection, and adduction not at all . Orbital CT-scan showed thinning of the inferior and lateral rectus muscles, but not of the medial rectus . Pol Arch Med Wewn, 2002 Jan, 107(1), 69 - 74 {Nitric oxide donors and their potentiating effects after botulinum toxin application for treatment of chronic anal fissure}; Madalinski M et al.; Pharmacological sphincterotomy with the use of botulinum toxin (BT) that inhibits acetylcholine secretion from neural endings in the motor plate or of nitric oxide (NO) donors should be a method applied earlier than surgical treatment due to its safety . BT mechanism of action on internal anal sphincter is not yet fully understood similarly to the effect of loosening of this sphincter under influence of NO donors applied after BT . Likewise paradoxical vasoconstrictive reaction on acetylcholine in the muscular layer of coronary arteries and decrease of tonic, vasodilative action of NO on the vessels may be observed in the patients with arterial hypertension . However, the muscle tissue of coronary arteries maintains the right dilative reaction on the endothelium independent NO donors . Local application of nitroglycerin is very safe and can be used by physicians in general practice for chronic anal fissure. Plast Reconstr Surg, 2002 Jun, 109(7), 2183 - 9 Surgical treatment of migraine headaches; Guyuron B et al.; This prospective study was conducted to investigate the role of removal of corrugator supercilii muscles, transection of the zygomaticotemporal branch of the trigeminal nerve, and temple soft-tissue repositioning in the treatment of migraine headaches . Using the criteria set forth by the International Headache Society, the research team's neurologist evaluated patients with moderate to severe migraine headaches, to confirm the diagnosis . Subsequently, the patients completed a comprehensive migraine headaches questionnaire and the team's plastic surgeon injected 25 units of botulinum toxin type A (Botox) into each corrugator supercilii muscle . The patients were asked to maintain an accurate diary of their migraine headaches and to complete a monthly questionnaire documenting pertinent information related to their headaches . Patients in whom the injection of Botox resulted in complete elimination of the migraine headaches then underwent resection of the corrugator supercilii muscles . Those who experienced only significant improvement underwent transection of the zygomaticotemporal branch of the trigeminal nerve with repositioning of the temple soft tissues, in addition to removal of the corrugator supercilii muscles . Once again, patients kept a detailed postoperative record of their headaches . Of the 29 patients included in the study, 24 were women and five were men, with an average age of 44.9 years (range, 24 to 63 years) . Twenty-four of 29 patients (82.8 percent, p < 0.001) reported a positive response to the injection of Botox, 16 (55.2 percent, p < 0.001) observed complete elimination, eight (27.6 percent, p < 0.04) experienced significant improvement (at least 50 percent reduction in intensity or severity), and five (17.2 percent, not significant) did not notice a change in their migraine headaches . Twenty-two of the 24 patients who had a favorable response to the injection of Botox underwent surgery, and 21 (95.5 percent, p < 0.001) observed a postoperative improvement . Ten patients (45.5 percent, p < 0.01) reported elimination of migraine headaches and 11 patients (50.0 percent, p < 0.004) noted a considerable improvement . For the entire surgical group, the average intensity of the migraine headaches reduced from 8.9 to 4.1 on an analogue scale of 1 to 10, and the frequency of migraine headaches changed from an average of 5.2 per month to an average of 0.8 per month . For the group who only experienced an improvement, the intensity fell from 9.0 to 7.5 and the frequency was reduced from 5.6 to 1.0 per month . Only one patient (4.5 percent, not significant) did not notice any change . The follow-up ranged from 222 to 494 days, the average being 347 days . In conclusion, this study confirms the value of surgical treatment of migraine headaches, inasmuch as 21 of 22 patients benefited significantly from the surgery . It is also evident that injection of Botox is an extremely reliable predictor of surgical outcome. Ophthalmology, 2002 Jun, 109(6), 1183 - 7 Treatment of upper eyelid retraction associated with thyroid eye disease with subconjunctival botulinum toxin injection; Uddin JM et al.; OBJECTIVE: To study the effectiveness of botulinum toxin injections, via a subconjunctival approach, in the management of upper eyelid retraction associated with thyroid eye disease . DESIGN: Prospective, non-comparative, interventional case series . PARTICIPANTS: Eleven patients with upper scleral exposure associated with thyroid eye disease who declined conservative or conventional surgical management . INTERVENTION: One or more treatments with injections of botulinum toxin into the subconjunctival space at the superior margin of the tarsal plate, via a conjunctival approach . MAIN OUTCOME MEASURES: Upper eyelid position in relation to the upper limbus, patient satisfaction, and complications . RESULTS: All patients experienced some improvement in the amount of lid retraction after injections . The amount of lid lowering varied between patients and lasted between 1 and 40 months . A lid position acceptable to the patient was obtained in 10 patients . Four patients had ptosis lasting from 1 to 3 weeks, and three patients had transient diplopia lasting 1 day to 3 weeks . CONCLUSIONS: This subconjunctival method of botulinum toxin injection provides an effective treatment for upper eyelid retraction associated with thyroid eye disease that is easy to administer and well tolerated by patients with few side effects. Curr Neurol Neurosci Rep, 2002 Jul, 2(4), 324 - 30 Management of essential tremor; Zesiewicz TA et al.; Essential tremor (ET) is the most prevalent tremor syndrome . It commonly affects the hands, head, voice, and other body parts . Appropriate management begins with correct diagnosis . Primidone and propranolol are the first-line medications for the treatment for ET, but several other medications may also provide benefit . In patients with medically refractory tremor, alternative therapies, including surgery or injections of botulinum toxin, may be considered. Rev Chir Orthop Reparatrice Appar Mot, 2002 May, 88(3), 279 - 85 {Botulinum toxin in the management of spastic hip adductors in non-ambulatory cerebral palsy children}; Deleplanque B et al.; PURPOSE OF THE STUDY: Spasticity of the hip adductors is a challenging problem for children with severe motor impairment due to cerebral palsy . It inhibits motor development and is also a risk factor for hip dislocation . Botulinum toxin has been found to be an effective means of treating spastic pes equinus in walking cerebral palsy patients and could have other indications . We conducted a prospective study to determine the functional and orthopedic contribution of botulinum toxin in the treatment of spastic hip adductors in non-ambulatory cerebral palsy children.MATERIAL AND METHODS: The study included 11 quadriplegic children with cerebral palsy (mean age 5 years 9 months) . Seven of the children had unilateral migration of the hip at study onset (> 40% radiographically) . The children were given a single injection of botulinum toxin (Dysport: 20 units/kg/hip) in the adductor muscles (21 treated hips) . The children were seen again at months 1, 3, 6 and 12 after treatment (with the exception of one patient not seen after the 6(th) month at the request of the parents) . Spasticity was measured with the modified Ashworth scale . The motor level was determined with 8 position and motor items and with the GMFCS classification . Hip x-rays were obtained at study onset and once or twice during the follow-up.RESULTS: There were no adverse effects of the treatment . Spasticity decreased by one point or more on the Ashworth scale in 20 hips at month 1 and remained low at month 3 in 14, and at month 6 in 12 of the 21 hips treated . The effect of the anti-spasticity treatment faded out from the 6(th) to the 12(th) month . Three children who experienced pain in the lower limbs were definitively relieved after treatment . Nine children achieved functional improvement (progress in at least one of the motor items) . Three children were able to walk with a walker and two of them improved from level IV to level III on the GMFCS . The best functional responses appeared to occur in the younger children and in those who had good results at months 3 and 6 . Among the 7 children whose hip was displaced by more than 40%, 5 had an unfavorable radiological progression and underwent surgery.DISCUSSION: This study demonstrates that the botulinum toxin can be effective against spasticity of the hip adductors and that its effect is still significant 6 months after the injection in more than half the hips treated . It has an analgesic effect . This treatment has a functional impact even in children with severe motor impairment . The benefit has been modest but three children were able to progress to walking with a walker . The best functional results were observed in the younger children and in those whose spasticity had declined at month 3 and 6 . It could thus be favored either by innate potential for motor development or by the treatment itself . The botulinum toxin did not improve the orthopedic prognosis of the children: 5 of the 7 with a risk of luxation worsened . Nevertheless, our study suggests that the botulinum toxin is a well-tolerated anti-spasticity treatment that is effective for the hip adductors providing an important contribution to the management of non-ambulatory cerebral palsy children. Eur Neurol, 2002, 47(4), 214 - 21 Low-dose botulinum toxin-a treatment of cervical dystonia - a double-blind, randomized pilot study; Laubis-Herrmann U et al.; The purpose of the study was to evaluate the clinical efficacy of low-dose botulinum toxin (BTX) treatment of cervical dystonia in a double-blind, randomized pilot study . Thirty-one patients with cervical dystonia and a minimum of 2 previous Dysport treatments received either a mean total target dose of 547 +/- 113 mouse units (MU) (group A, 500 MU Dysport/ml) or a 4-times-diluted preparation 130 +/- 32 MU (group B, 125 MU Dysport/ml) . Assessment was made before and 4 weeks after the injection using Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS) . Additionally, a self-response scale evaluated the patients' subjective condition for 12 weeks after injection . TWST rating before and after injection revealed comparable clinical improvement in both groups . The severity of cervical dystonia at study entry had no effects on therapeutic effects of either preparation . Self-rating revealed comparable subjective improvement in both groups; however, 3 patients of group B received reinjections due to insufficient effects of the injection . Our findings suggest that low-dose treatment of cervical dystonia with Dysport may be clinically effective during maintenance therapy, at least for a limited period of time . Long-lasting effects of previous Dysport treatments at conventional doses and possibly improved diffusion of a highly diluted toxin preparation may have contributed to the effects of the low-dose regimen . Our data emphasize the need for further studies in order to clearly identify optimal toxin preparations for therapeutic uses of BTX-A in neurologic disorders . Am J Ophthalmol, 2002 Jun, 133(6), 854 - 6 Hemifacial spasm caused by vertebral artery dolichoectasia; Rahman EA et al.; PURPOSE: To display the characteristic magnetic resonance imaging (MRI) abnormalities associated with hemifacial spasm caused by compression of the seventh cranial nerve by a dolichoectatic vertebral artery . DESIGN: Interventional case report . METHODS: Correlation of imaging and clinical findings . RESULTS: In a 36-year-old man with mild left hemifacial spasm, MRI showed an enlarged (dolichoectatic) vertebral artery that compressed the seventh cranial nerve at its exit from the caudal pons . Manifestations of hemifacial spasm were relieved with periocular botulinum toxin injections . CONCLUSION: In hemifacial spasm, MRI may show compression of the ipsilateral seventh cranial nerve or other structural abnormalities . Relief of hemifacial spasm may occur with botulinum toxin injection or with neurosurgical intervention designed to relieve the compression. Ugeskr Laeger, 2002 Apr 29, 164(18), 2402 - 5 {Chronic idiopathic anal pain syndrome}; Christiansen J et al.; INTRODUCTION: The study was undertaken to analyse whether intra-anal ultrasound examination, anorectal physiological evaluation, and histopathological examination of patients suffering from chronic idiopathic anal pain presented any common features and to analyse the results of various treatments . MATERIAL AND METHODS: Eighteen patients who met the criteria for chronic idiopathic anal pain were studied . Treatment included 0.2% glyceryl nitrate ointment, ultrasound guided injection of botulinum toxin in the intrasphincteric space, analgesics, and colostomy . RESULTS: Anal physiological examinations were normal in all but one patient . Intra-anal ultrasonography demonstrated abnormalities in 12 patients . Defecography showed in one patient a small distal invagination but was otherwise normal . Glyceryl nitrate ointment had an effect in one of four patients, and botulinum toxin in four of nine . Two patients needed a colostomy for definitive pain relief, and in 12 of the 18 patients the final treatment was analgesics . DISCUSSION: The methods used in this study did not contribute to the understanding of the pathogenesis of chronic anal pain . The treatment is experimental, but injection of botulinum toxin may be tried on the hypothesis that dystonia in the anal sphincter may play a pathogenetic role. Gastrointest Endosc, 2002 Jun, 55(7), 920 - 3 Pyloric injection of botulinum toxin for treatment of diabetic gastroparesis; Ezzeddine D et al.; BACKGROUND: Diabetic gastroparesis is a common clinical problem . The pathophysiology includes prolonged pyloric contractions that may cause functional resistance to gastric outflow . Botulinum toxin was injected into the pyloric sphincter in an attempt to decrease pyloric resistance and improve gastric emptying . METHODS: Six patients with diabetic gastroparesis and an abnormal solid phase gastric emptying study underwent upper endoscopy during which 100 units of botulinum toxin were injected into the pyloric sphincter . Gastric emptying studies were obtained at 48 hours and 6 weeks after injection . Patients were questioned about symptoms of gastroparesis, and a symptom score was obtained at baseline and at 2 weeks and 6 weeks after injection . OBSERVATIONS: There was a mean improvement in the subjective symptom score at 2 weeks of 55% (range 14% to 80%) . This improvement was maintained at 6 weeks . There was a 52% improvement in gastric emptying at 2 and 6 weeks . CONCLUSION: Pyloric injection of botulinum toxin can improve symptoms and gastric emptying in patients with diabetic gastroparesis . Further evaluation of pyloric injection of botulinum toxin as a treatment for diabetic gastroparesis is warranted. J Pharmacol Exp Ther, 2002 Jun, 301(3), 953 - 62 Pardaxin stimulation of phospholipases A2 and their involvement in exocytosis in PC-12 cells; Bloch-Shilderman E et al.; Pardaxin (PX) is a voltage-dependent ionophore that stimulates catecholamine exocytosis from PC-12 pheochromocytoma cells both in the presence and absence of extracellular calcium . Using a battery of phospholipase A(2) inhibitors we show that PX stimulation of phospholipase A(2) (PLA(2)) enzymes is coupled with induction of exocytosis . We investigated the relationship between PX-induced PLA(2) activity and neurotransmitter release by measuring the levels of arachidonic acid (AA), prostaglandin E(2) (PGE(2)), and dopamine release . In the presence of extracellular calcium, the cytosolic PLA(2) inhibitor arachidonyl trifluoromethyl ketone (AACOCF(3)) inhibited by 100, 70, and 73%, respectively, the release of AA, PGE(2), and dopamine induced by PX . The mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor 2'-amino-3'-methoxyflavone (PD98059) reduced by 100 and 82%, respectively, the release of AA and PGE(2) induced by PX . In the absence of extracellular calcium, the calcium-independent PLA(2) (iPLA(2)) inhibitors methyl arachidonyl fluorophosphonate, AACOCF(3), and bromoenol lactone (BEL) inhibited by 80 to 90% PX stimulation of AA release, by 65 to 85% PX stimulation of PGE(2) release, and by 80 to 90% PX-induced dopamine release . Using vesicle fusion-based enzyme-linked immunosorbent assay we found similar levels of inhibition of PX-induced exocytosis by these inhibitors . Also, PX induced the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complexes, an effect that was augmented by N-methylmaleimide . This complex formation was completely inhibited by BEL . Botulinum toxins type C1 and F significantly inhibited the release of AA, PGE(2), and dopamine induced by PX . Our data suggest that PX stimulates exocytosis by activating cystolic PLA(2) and iPLA(2), leading to the generation of AA and eicosanoids, which, in turn, stimulate vesicle competence for fusion and neurotransmitter release. J Gastrointest Surg, 2002 May-Jun, 6(3), 368 - 76; discussion 377-78 Development of achalasia secondary to laparoscopic Nissen fundoplication; Stylopoulos N et al.; Dysphagia after laparoscopic Nissen fundoplication (LNF) is commonly attributed to edema and/or improperly constructed wraps, and in some instances the cause can be difficult to identify . We report, for the first time, the development of secondary achalasia after LNF as a cause of late-onset postoperative dysphagia . A total of 250 consecutive patients undergoing LNF were analyzed for the development of postoperative dysphagia at a university hospital . Patients were considered to have secondary achalasia if they met the following four criteria: (1) preoperative manometry demonstrating normal peristalsis and normal lower esophageal sphincter (LES) relaxation; (2) lack of esophageal peristalsis on postoperative manometry or fluoroscopy with or without incomplete LES relaxation; (3) no mucosal lesions seen on endoscopy; and (4) dysphagia refractory to dilatation . The following three groups of patients were identified: patients who developed secondary achalasia (group A, n = 7); patients with persistent dysphagia requiring and responding to postoperative dilatation (group B, n = 12 patients); and patients whose postoperative recovery was not complicated by dysphagia (group C, n = 231) . The groups were comparable in terms of all preoperative variables except for age . Patients in group A were older than those in group B (57 years {range 27 to 66 years} vs . 36.5 years {range 27 to 63 years}, P = 0.028) but were not significantly older than patients in group C (45 years {range 20 to 84 years}, P = 0.42) . The onset of severe dysphagia was later in group A than in group B (135 days {range 15 to 300 days} vs . 20 days {range 9 to 70 days}, P = 0.002) . The median weight loss in group A was also significantly greater than in Group B (15 pounds {range 11 to 44 pounds} vs . 4 pounds {range 0 to 15 pounds}, P = 0.0007) . Two patients in group A who underwent reoperation failed to improve . Botulinum toxin injections were tried in two patients and Heller myotomy in one with good results . Nine patients in group B improved promptly after one dilatation, and three improved after two dilatations . Secondary achalasia should be considered as one of the causes of persistent dysphagia after an apparently successful antireflux operation . Secondary achalasia tends to occur in older patients and is characterized by a delayed onset of symptoms . Imaging studies are a reliable means of excluding mechanical obstruction as a cause of secondary achalasia, and a negative result should raise the suspicion of secondary achalasia . Esophageal motility studies are necessary to confirm the diagnosis . Failure to consider the diagnosis of secondary achalasia can lead to multiple fruitless attempts at dilatation or even inappropriate reoperations. Aesthetic Plast Surg, 2002 Mar-Apr, 26(2), 89 - 98 New indications for botulinum toxin type A in treating facial wrinkles of the mouth and neck; Sposito MM; Botulinum toxin type A (BTX-A) is commonly used to smooth hyperkinetic lines in the periocular and forehead areas of the upper face, but has been used less frequently for indications in the lower face and neck . This study was designed to determine whether botulinum toxin treatment of the mouth and neck areas is as clinically successful as treatment of the upper face . This was a retrospective study of patients who were treated with botulinum toxin type A (BOTOX, Allergan, Inc) to soften hyperkinetic facial wrinkles . Of 100 patients randomly selected from a single clinical practice, 91 met the inclusion criteria and were divided into two groups for analysis: the 56 patients in Group 1 did not receive treatment in the mouth and neck areas, while the 35 patients in Group 2 were treated at least once in the mouth and neck areas . Patients were surveyed for periods ranging from seven to 49 months . Most patients in each group had a single BTX-A procedure during this period . Both groups of patients had comparable improvement of wrinkles both at the evaluation immediately after the neuromuscular blockade and during followup . In comparison with patients whose treatment was confined to the upper face, patients who received global treatment with BTX-A, including BTX-A injections in the mouth and neck areas, were injected in more sites per procedure and had more procedures in combination with other therapies . Patient satisfaction with botulinum toxin treatment and outcomes was high in both groups . BTX-A is an important tool within the therapeutic spectrum for the treatment of hyperkinetic facial wrinkles, including those in the areas of the mouth and neck. J Rehabil Med, 2002 Mar, 34(2), 51 - 61 Treatment of upper extremity spasticity in stroke patients by focal neuronal or neuromuscular blockade: a systematic review of the literature; van Kuijk AA et al.; Studies published from January 1966 until October 2000 on the clinical effects of focal neuronal and neuromuscular blockade in post stroke upper limb spasticity were identified . Twelve studies were included and evaluated on 13 methodological criteria . Ten studies on Botulinum toxin type A (BTX-A) treatment were found (of which 4 were randomised controlled trials (RCTs) and 6 were uncontrolled observational studies) as well as one uncontrolled observational study on phenol blockade of the subscapular muscle and one on alcohol blockade of the musculocutaneus nerve . The homogeneity of the patient groups with regard to diagnosis and their comparability with regard to functional prognosis and other sources of bias were generally unsatisfactory . Only two RCTs met predetermined criteria of minimal validity . There is evidence of effectiveness of BTX-A treatment on reducing muscle tone (varying between 0.8 and 2.0 points on the modified Ashworth scale) and improving passive range of motion at all arm-hand levels in chronic stroke patients for approximately 3-4 months . There is also preliminary evidence of a synergistic effect of concomitant electrostimulation . Taking into account a critical maximum dose of 100 MU Botox" (300-500 MU Dysport) for preserving active finger flexion, BTX-A treatment seems to be a safe focal spasmolytic treatment . Effectiveness of BTX-A treatment on improving functional abilities could not be convincingly demonstrated, although two subgroups may be identified that might specifically benefit at a functional level: (1) patients with mild spasticity and a potential for voluntary extensor activity and (2) patients with severe spasticity suffering from problems with positioning and taking care of the affected arm and hand . Larger controlled studies are needed to compare the effectiveness of BTX-A with other focal spasmolytic techniques paying special attention to individual goal assessment, the (duration of) functional benefits, co-treatment and aftercare, side-effects and cost-effectiveness. Arch Esp Urol, 2002 Mar, 55(2), 167 - 76 {Review of the use of botulinum toxin in urology}; Chavarria Mendoza J et al.; OBJECTIVE: There are several procedures for the management and treatment of the neurogenic bladder . These are adjusted individually according to the results of the clinical examination and complementary tests . This study evaluates the results of treatment with botulinum toxin and its place in current therapeutic armamentarium . METHODS: We reviewed the outstanding literature in the field of neurorology on the criteria, indications, side effects and applications of botulinum toxin . RESULTS: Most of the authors have reported botulinum toxin to be useful in the treatment of voiding disorders secondary to neurological and pelvic floor muscle disorders . CONCLUSIONS: Intramuscular injection of botulinum toxin in the detrusor or external sphincter of the bladder produces a paralyzing (relaxing), therapeutic and reversible effect . The latter is one of its most important characteristics . It has also been found to be effective for non-specific perineal-prostatic pain, for which few treatments are available. J Voice, 2002 Mar, 16(1), 124 - 31 The effect of botulinum toxin A on the vocal symptoms of spastic dysarthria: a case study; McHenry M et al.; The vocal symptoms of spastic dysarthria and spasmodic dysphonia have many similar features . Botulinum toxin has been used effectively to treat spasmodic dysphonia . This study was designed to determine what vocal changes occur in an individual with spastic dysarthria following Botulinum toxin A injection into the thyroarytenoid muscles . Measures were obtained preinjection and three times postinjection . Acoustic and aerodynamic results were comparable to those reported for individuals with spasmodic dysphonia . The most marked change was increased DC airflow . Despite persistent breathiness, the participant reported great satisfaction with the result, particularly because of her more appropriate loudness . In addition, everyday listeners perceived significantly less listener burden and more relaxed and pleasant vocal quality postinjection. J Voice, 2002 Mar, 16(1), 117 - 23 Unilateral versus bilateral injections of botulinum toxin in patients with adductor spasmodic dysphonia; Bielamowicz S et al.; Both unilateral and bilateral thyroarytenoid muscle injections of Botox provide effective management of voice symptoms in patients with adductor spasmodic dysphonia; however, the preferred injection technique has not been established . In this study, 16 patients were treated with unilateral injections (72 injections total) and 33 patients were managed with bilateral injections (133 injections total) . Individual assignments to injection type were based on treatment previously received and dose was adjusted according to the patient's previous treatment response . An optimal treatment included a benefit lasting 3 months or more with side effects lasting 2 weeks or less . Compared to patients receiving bilateral injections, those receiving unilateral injections more frequently noted a benefit of 3 months or more (p = 0.03), side effects of 2 weeks or less duration (p = 0.03), as well as both a 3-month benefit and a 2-week or less side effect (p = 0.0004) . Injection type had no effect on optimal Botox dosing with repeat injections . Successive unilateral injections at the same dose were more likely (p = 0.012) than successive bilateral injections to produce the same or longer duration of benefit . We conclude that a unilateral injection routine has a more optimal and consistent treatment effect/side effect profile. Neurol Neurochir Pol, 2001, 35 Suppl 3, 23 - 7 Botulinum toxin for treatment of parkinsonian sialorrhea; Friedman A et al.; AIM: Sialorrhea is one of the main problems of patients with Parkinson's disease (PD) . Most of the medications used for the treatment of it are ineffective . We decided to try in such patients local injections of botulinum toxin, type A, into both parotid glands . MATERIAL: 11 patients with clinical diagnosis of idiopathic PD and drooling assessed as at least 2 point on the UPDRS part II and 14 control subjects . METHODS: Salivation was measured by weighting dental rolls before and 2 minutes after insertion at 6 places of highest secretion of saliva in mouth (buccal vestibule, and sublingual area) . PD patients were assessed before and one week after injections of 5 units of BOTOX into each parotid salivary gland and the results were compared to the salivation of controls . RESULTS: Average excretion of saliva in PD patients was significantly higher than in controls -0.39 +/- 0.4 g/2 min . (range: 0.02-1.82) vs . 0.19 +/- 0.16 g/2 min . (range: 0.02-0.98) (p = 0.03) . After the treatment the average excretion of saliva in PD patients decreased to 0.25 +/- 0.26 g/2 min . (range: 0.004-0.99) and did not differ significantly from controls . All patients improved also according to UPDRS . No side-effects were observed in any of the patients injected . CONCLUSION: Botulinum toxin may be an effective and safe treatment of parkinsonian sialorrhea. Int Urogynecol J Pelvic Floor Dysfunct, 2002, 13(1), 55 - 6 Botulinum toxin urethral sphincter injection resolves urinary retention after pubovaginal sling operation; Smith CP et al.; The management of prolonged urinary retention following pubovaginal sling surgery typically involves transvaginal urethrolysis for anatomical urethral obstruction . Brubaker recently reported on urethral sphincter abnormalities as a cause of postoperative urinary retention following either Burch suspension or a pubovaginal sling procedure . We report a case of functional urethral obstruction and detrusor acontractility following pubovaginal sling surgery that was successfully treated by botulinum A toxin urethral sphincter injection. J AAPOS, 2002 Apr, 6(2), 77 - 80 Surgical results in large-angle exotropia; Livir-Rallatos G et al.; PURPOSE: This study examines the surgical results of correcting large angle exodeviations in adults who may lack bifixation . The expected results in adults are not to achieve improved fusion but, rather, to construct the alignment . METHODS: A retrospective chart review was conducted of all patients with comitant exodeviation greater than 35 Delta examined and treated by 1 pediatric ophthalmologist between January 1994 and May 1999 . Any patients with large A or V patterns, nystagmus, history of botulinum toxin injections for strabismus, paralytic or mechanical cause for strabismus, or use of adjustable sutures were excluded . Charts were reviewed for postoperative alignment . Postoperative results were separated into 3 categories: exodeviation greater than 10 Delta, successful outcome (esotropia<10 Delta, orthotropia, or exodeviation <10 Delta), or esotropia greater than 10 Delta . RESULTS: Sixty-three patients met the inclusion criteria . Their median age at the time of surgery was 18, with a standard deviation of 20 . The majority of them had intermittent exotropia that had deteriorated into constant exotropia . Fifty-two patients had bilateral lateral rectus recessions, and 11 patients had recess/resect procedures . Sixty-two percent (39 of 63) had successful outcomes overall . Only 2 patients had overcorrection (esotropia>10 Delta) . In patients with deviations greater than 50 Delta, 82% (9 of 11) were undercorrected (exodeviation >10 Delta) . CONCLUSIONS: Large-angle exodeviations can be successfully approached with bilateral lateral rectus recessions or recess/resect procedures in preoperative deviations up to and including 50 Delta with a success rate of 71% . In larger deviations, 2-muscle surgery was not as successful (18%, or 2 of 11). J Neurol, 2002 Mar, 249(3), 300 - 4 Botulinum toxin treatment in atypical parkinsonian disorders associated with disabling focal dystonia; Muller J et al.; We investigated the efficacy of botulinum toxin A (BtxA) therapy in patients with atypical parkinsonian disorders (APD) exhibiting different types of disabling focal dystonia unresponsive to oral drug therapy . Eight patients with functionally disabling focal dystonia out of a series of 60 consecutive patients with APDs regularly treated at our outpatient movement disorders clinic were included . Patients were diagnosed according to established criteria and had disabling limb dystonia (n=4) or craniocervical dystonia (n=4) unresponsive to oral pharmacological treatment . Localization and dose of BtxA injections was determined individually based on clinical examination as well as EMG in patients with limb dystonia . BtxA reduced dystonic symptoms in all patients; only one developed a transient local side-effect . BtxA was particularly effective in the long-term treatment (up to 50 months) of blepharospasm associated with progressive supranuclear palsy (PSP) . BtxA also alleviated PSP-associated retrocollis and orofacial dystonia with lower lip retraction associated with PSP and multiple system atrophy . BtxA treatment of limb dystonia in corticobasal degeneration (CBD) temporarily improved hand and arm function in early-disease stages while treatment in advanced stages reduced pain, facilitated hygiene and prevented secondary contractures . Limb dystonia was also alleviated by BtxA therapy in one patient with neuronal multisystem degeneration of undetermined cause . The results suggest that BtxA therapy may represent an effective means of alleviating disabling focal dystonia in different APDs . Particularly in early stage APD with disabling limb dystonia local BtxA injections may result in functional improvement. Pediatr Neurol, 2002 Apr, 26(4), 318 - 20 Treatment of dystonia in striatal necrosis caused by Mycoplasma pneumoniae; Green C et al.; We report on an 8-year-old male with bilateral striatal necrosis secondary to Mycoplasma pneumoniae respiratory infection . This patient has been remarkable for persistent severe dystonia that has been difficult to treat . We share our experience of beneficial responses to multimodal treatment, including moderate doses of trihexyphenidyl, botulinum toxin, and intrathecal baclofen. Clin Med, 2002 Mar-Apr, 2(2), 128 - 30 Botulinum toxin in the management of spasticity in adults; Turner-Stokes L et al.; Botulinum toxin (BTX) is a powerful neurotoxin which blocks cholinergic transmission at the neuromuscular junction . Judiciously applied, it can reduce local muscle overactivity while maintaining the strength in other muscles . To date BTX has not been licensed for use in spasticity in the UK and the literature pertaining to clinical practice is still relatively scant . However, controlled trials have provided evidence of the effectiveness of BTX both in reducing spasticity itself and in achieving functional gain . The guidance given here to clinicians involved in the management of spasticity covers the types of patient suitable for treatment using BTX, the appropriate dosage, and the necessary follow-up procedures and documentation. Rev Neurol, 2002 Jan 1-15, 34(1), 52 - 9 {Treatment of spasticity in cerebral palsy with botulinum toxin}; Calderon-Gonzalez R et al.; OBJECTIVE: A review of the pathophysiological and developmental basis, measurement scales and the usefulness of botulinum toxin A injections in selected muscles for the treatment of spasticity in children with cerebral palsy . DEVELOPMENT: Cerebral palsy is the most common cause of spasticity in children . The increase in muscle length is achieved through the addition of sarcomeres in series at the level of the muscle tendinous junction . The regulation of the number of sarcomeres seems to be determined by the lengthening of the muscle . The muscle contracture is a shortening of the length of a muscle as a result of a decrease in the number of sarcomeres . Spasticity and motor function assessment scales used in children with cerebral palsy: a) Modified Ashworth scale for the assessment of spasticity; b) modified Tardieu scale for the assessment of dynamic muscle length; c) muscle spasms frequency scale; d) modified Medical Research Council scale for muscle strength; e) hip adductor muscle tone scale; f) global pain scale with affective facial expression represented in a drawing; g) goniometric measurement of the joint range of movement; h) Palisano gross motor function measure; i) observational video gait analysis scale . Recommended guidelines for dosing the botulinum toxin A: 1 . Total maximum dose administered per visit up to 15 U/kg or a total of 400 U; 2 . Dose range of large muscles 3 to 6 U/kg per visit; 3 . Dose range of small muscles 1 to 3 U/kg per visit; 4 . Maximum dose per injection site: 50 U dividing the total planned unit dose/muscle into equal amounts/injection site; 5 . Frequency: no more than one injection every 3 months, frequently once every 6 or more months . CONCLUSION: Botulinum toxin A injection is a well tolerated, safe and effective procedure in the treatment of children with spastic cerebral palsy. Rev Neurol, 2002 Jan 1-15, 34(1), 1 - 6 {Clinical treatment (non surgical) of spasticity in cerebral palsy}; Calderon-Gonzalez R et al.; OBJECTIVE: A review about the procedures used in the non surgical management of spasticity in children with cerebral palsy . DEVELOPMENT: Therapeutic modalities for the management of spasticity in cerebral palsy include: (1) elimination of factors aggravating spasticity: pain, fatigue, stress, excitement, cold, illness, sleep disturbance, immobility, and hormonal changes; (2) rehabilitative therapies, there are four major groups: (a) biomechanical approach, (b) neurophysiologic approach, (c) developmental approach and (d) sensory approach; (3) orthosis; (4) oral pharmacotherapy: baclofen, tizanidine, diacepam and dantroleno; (5) chemical denervation: phenol injections and botulinum toxin injections . The medical management of spasticity in cerebral palsy is based on: 1 . Oral pharmacotherapy: (a) baclofen, binds GABAB receptors of spinal interneurons presynaptically, inhibits release of excitatory neurotransmitters in the spinal cord; (b) tizanidine, binds alfa 2 adrenergic receptors presinaptically, inhibits release of excitatory neurotransmitters in the spinal cord; (c) diacepam, augments GABA mediated inhibition in the spinal cord and supraspinally;(d) dantrolene, inhibits release of calcium from sarcoplasmic reticulum in muscle, weakens muscle contraction in response to myofiber excitation . 2 . Chemical denervation: (a) phenol injection perineurally or into the motor point disrupts efferent signals from hyperexcitable anterior horn cells causing necrosis of axons or muscle; (b) botulinum toxin injection in selected muscles blocks the release of acetylcholine presynaptically and weakens the force of muscle contraction produced by hyperexcitable motoneurons . CONCLUSIONS: At the present time, there is not irrefutable evidence of a sustain benefit of physical rehabilitation in the management of spasticity . There are few studies with oral pharmacological agents involving children with cerebral palsy to define its role . On the other hand, botulinum toxin A is effective, well tolerated, and safe in the treatment of spasticity in children with cerebral palsy. Ann Surg, 2002 May, 235(5), 631 - 8; discussion 638-9 100 consecutive minimally invasive Heller myotomies: lessons learned; Sharp KW et al.; OBJECTIVE: To evaluate the authors' first 100 patients treated for achalasia by a minimally invasive approach . METHODS: Between November 1992 and February 2001, the authors performed 95 laparoscopic and 5 thoracoscopic Heller myotomies in 100 patients (age 49.5 +/- 1.5 years) with manometrically confirmed achalasia . Before presentation, 51 patients had previous dilation, 23 had been treated with botulinum toxin (Botox), and 4 had undergone prior myotomy . Laparoscopic myotomy was performed by incising the distal 4 to 6 cm of esophageal musculature and extended 1 to 2 cm onto the cardia under endoscopic guidance . Fifteen patients underwent antireflux procedures . RESULTS: There were eight intraoperative perforations and only four conversions to open surgery . Follow-up is 10.8 +/- 1 months; 75% of the patients have been followed up for at least 14 months . Outcomes assessed by patient questionnaires revealed satisfactory relief of dysphagia in 93 patients and "poor" relief in 7 patients . Postoperative heartburn symptoms were reported as "moderate to severe" in 14 patients and "none or mild" in 86 patients . Fourteen patients required postoperative procedures for continued symptoms of dysphagia after myotomy . Esophageal manometry studies revealed a decrease in lower esophageal sphincter pressure (LESP) from 37 +/- 1 mm Hg to 14 +/- 1 mm Hg . Patients with a decrease in LESP of more than 18 mm Hg and whose absolute postoperative LESP was 18 or less were more likely to have relief of dysphagia after surgery . Thirty-one patients who underwent Heller alone were studied with a 24-hour esophageal pH probe and had a median Johnson-DeMeester score of 10 (normal <22.0) . Mean esophageal acid exposure time was 3 +/- 0.6% (normal 4.2%) . Symptoms did not correlate with esophageal acid exposure . CONCLUSIONS: The results after minimally invasive treatment for achalasia are equivalent to historical outcomes with open techniques . Satisfactory outcomes occurred in 93% of patients . Patients whose postoperative LESP was less than 18 mm Hg reported the fewest symptoms . After myotomy, patients rarely have abnormal esophageal acid exposure, and the addition of an antireflux procedure is not required. Diabetes, 2002 May, 51(5), 1425 - 36 Modulation of L-type Ca(2+) channels by distinct domains within SNAP-25; Ji J et al.; Cognate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are now known to associate the secretory vesicle with both the target plasma membrane and Ca(2+) channels in order to mediate the sequence of events leading to exocytosis in neurons and neuroendocrine cells . Neuroendocrine cells, particularly insulin-secreting islet beta-cells, t-SNARE proteins, 25-kDa synaptosomal-associated protein (SNAP-25), and syntaxin 1A, independently inhibit the L-type Ca(2+) channel (L(Ca)) . However, when both are present, they actually exhibit stimulatory actions on the L(Ca) . This suggests that the positive regulation of the L(Ca) is conferred by a multi-SNARE protein complex . We hypothesized an alternate explanation, which is that each of these SNARE proteins possess distinct inhibitory and stimulatory domains that act on the L(Ca) . These SNARE proteins were recently shown to bind the Lc(753-893) domain corresponding to the II and III intracellular loop of the alpha1C subunit of the L(Ca) . In this study, using patch-clamp methods on primary pancreatic beta-cells and insulinoma HIT-T15 cells, we examined the functional interactions of the botulinum neurotoxin A (BoNT/A) cleavage products of SNAP-25, including NH(2)-terminal (1-197 amino acids) and COOH-terminal (amino acid 198-206) domains, on the L(Ca), particularly at the Lc(753-893) domain . Intracellular application of SNAP-25(1-206) in primary beta-cells decreased L(Ca) currents by approximately 15% . The reduction in L(Ca) currents was counteracted by coapplication of Lc(753-893) . Overexpression or injection of wild-type SNAP-25 in HIT cells reduced L(Ca) currents by approximately 30%, and this inhibition was also blocked by the recombinant Lc(753-893) peptide . Expression of BoNT/A surprisingly caused an even greater reduction of L(Ca) currents (by 41%), suggesting that the BoNT/A cleavage products of SNAP-25 might possess distinct inhibitory and positive regulatory domains . Indeed, expression of SNAP-25(1-197) increased L(Ca) currents (by 19% at 10 mV), and these effects were blocked by the Lc(753-893) peptide . In contrast, injection of SNAP-25(198-206) peptide into untransfected cells inhibited L(Ca) currents (by 47%), and more remarkably, these inhibitory effects dominated over the stimulatory effects of SNAP-25(1-197) overexpression (by 34%) . Therefore, the SNARE protein SNAP-25 possesses distinct inhibitory and stimulatory domains that act on the L(Ca) . The COOH-terminal 197-206 domain of SNAP-25, whose inhibitory actions dominate over the opposing stimulatory NH(2)-terminal domain, likely confers the inhibitory actions of SNAP-25 on the L(Ca) . We postulate that the eventual accelerated proteolysis of SNAP-25 brought about by BoNT/A cleavage allows the relatively intact NH(2)-terminal SNAP-25 domain to assert its stimulatory action on the L(Ca) to increase Ca(2+) influx, and this could in part explain the observed weak or inconsistent inhibitory effects of BoNT/A on insulin secretion . The present study suggests that distinct domains within SNAP-25 modulate L(C) subtype Ca(2+) channel activity in both primary beta-cells and insulinoma HIT-T15 cells. Eur J Dermatol, 2002 May-Jun, 12(3), 219 - 23 Current therapeutic strategies for hyperhidrosis: a review; Togel B et al.; Overproduction of sweat by the exocrine sweat glands is called hyperhidrosis . It is differentiated into two forms - a localised (e.g . axillary, palmar and plantar hyperhidrosis) and a generalised form that affects the entire skin . Patients with increased sweat production often suffer from enormous psychosocial stress because they are restricted in both their private and professional lives . If the hyperhidrosis is not caused by a primary disease (e.g . hyperthyroidism or phaeochromocytoma) that can be treated, with elimination of the sweating problem, then only symptomatic treatment is possible . For axillary hyperhidrosis, local application of aluminium chloride seems to be the method of choice; an alternative is botulinum toxin whose efficacy for 3 to 9 months is an advantage . Surgical options should not be considered until conservative methods have failed . Curettage with a scraper and liposuction are reliable and safe treatments for axillary hyperhidrosis . The method of choice in treating palmoplantar hyperhidrosis is tap water iontophoresis . Adding anticholinergic substances to the water produces a more rapid therapeutic success that also lasts longer . Botulinum toxin can be an effective and promising alternative . Surgical treatment, i.e . sympathectomy, does bring about a long-term resolution of the problem, but should only be considered in well-justified cases because of the highly invasive character of the procedure . The use of systemic anticholinergic medication for patients with localised or generalised tendency to sweat can be tried, but is often limited because of the profile of adverse effects . It can be stated that in spite of the interesting and promising new alternatives, especially using botulinum toxin, the tried-and-true procedures such as tap water iontophoresis and aluminium chloride salts still have a firm place in the treatment of hyperhidrosis. Nervenarzt, 2002 Feb, 73(2), 194 - 8 {Initial experiences with clinical use of botulinum toxin type B}; Dressler D et al.; Recently, botulinum toxin type B (BT-B) was introduced for treatment of cervical dystonia (CD) . We wish to report on experience with BT-B derived from registration studies and from our own preliminary clinical experience . Botulinum toxin type B can be used successfully in CD patients with antibody-induced failure of botulinum toxin type A therapy (antibody patients) . In our own 15 antibody patients, 11835 +/- 2,039 mouse units of BT-B (NeuroBloc) reduced the Toronto Western spasmodic torticollis rating scale (TWSTRS) score from 20.5 +/- 3.6 to 13.1 +/- 5.4 . BT-B can also be used successfully in CD patients not previously exposed to BT-A or BT-B (de novo patients) . In our own nine de novo patients, 10436 +/- 3,320 mouse units of BT-B reduced the TWSTRS score from 18.4 +/- 5.4 to 9.2 +/- 4.8 . Altogether, dryness of the mouth occurred in 21 CD patients (severe 10, moderate 7, mild 4), accommodation difficulties in seven, conjunctival irritation in five, reduced sweating in four, swallowing difficulties in three, heartburn in three, constipation in three, bladder voiding difficulties in two, and dryness of nasal mucosa, head instability, and thrush in one each . BT-B produces substantially more systemic autonomic side effects than BT-A . It can be considered the therapy of choice in antibody patients . For de novo patients and for BT-A-treated CD patients, BT-B cannot be recommended currently. Acta Neurochir Suppl, 2002, 79, 123 - 6 Botulinum toxin (DYSPORT) in tension-type headaches; Rollnik JD et al.; OBJECTIVES: Botulinum toxin type A is effective in the reduction of muscle tenderness and pain in many diseases associated with myofascial pain . Since increased muscle tension may contribute to tension-type headaches, injections of botulinum toxin could be of therapeutic value . METHODS/PATIENTS: Results of own investigations are presented, in particular a double-blind, placebo-controlled study with 21 patients fulfilling the International Headache Society criteria for tension-type hedaches . Participants were randomly assigned to verum (pericranial injection of 10 x 20 MU DYSPORT) or placebo condition (injection of isotonic saline in the same manner) . RESULTS: After 4, 8, and 12 weeks no significant differences between placebo and verum could be observed . Nevertheless, both groups significantly improved . DISCUSSION: The findings strongly suggest that higher doses or other injection sites might be necessary to achieve therapeutic effects of botulinum toxin in tension-type headaches . Actually, we are participating in a multi-center study using 500 MU of DYSPORT . Besides dose-finding problems, another explanation could be that peripheral mechanisms--such as increased pericranial muscle tension--only play a minor role in the pathogenesis of tension-type headaches. Acta Neurochir Suppl, 2002, 79, 117 - 22 Management of upper and lower limb spasticity in neuro-rehabilitation; Hesse S et al.; This article reviews the treatment of upper and lower limb spasticity in neurological rehabilitation . Botulinum toxin A proved effective in several placebo-controlled studies reducing muscle tone, easing hand hygiene and nursing, improving upper limb motor functions and gait ability . The effects are reversible and the toxin is well tolerated . Electrical stimulation, tonic stretch post injection and the active use of the treated extremity are means to increase the effectiveness of the costly therapy . Phenol 5% is an alternative in case of budget constraints, but the technique is demanding and side effects are more frequent . Further, task-specific repetitive therapy should follow the successful treatment of focal spasticity in eligible patients to get the maximum profit with regard to disability. J Neurol Neurosurg Psychiatry, 2002 May, 72(5), 608 - 14 What are the determinants of quality of life in people with cervical dystonia? Ben-Shlomo Y, Camfield L, Warner T; ESDE collaborative group. BACKGROUND: Little is known about the quality of life in patients with cervical dystonia, although pain and depression are relatively common . OBJECTIVE: To test the hypothesis that an individual's ability to cope with the disease will modify the association of intrinsic, extrinsic, and disease related factors with quality of life . METHODS: Patients with cervical dystonia diagnosed by a movement disorder specialist were recruited from seven European countries . Data on quality of life (SF-36), measures of coping, and intrinsic, extrinsic, and disease related factors were collected by a self completed postal questionnaire . RESULTS: 289 patients (101 men and 188 women), mean age 55 years, completed the questionnaire . Both physical and mental quality of life scores were predicted by self esteem and self deprecation, educational level, employment status, social support, response to botulinum toxin, disease severity, social participation, stigma, acceptance of illness, anxiety, and depression . In multivariable analyses, the strongest predictors were anxiety and depression . Severe depression was associated with a 19.1 point decrement in the physical summary score (95% confidence interval, -31.7 to -6.6; p = 0.003); however, disease duration and severity remained predictors . CONCLUSIONS: Care for patients with cervical dystonia must not only focus on reducing the severity of the dystonia but also on the psychological wellbeing of the patient . Interventions aimed at treating depression or anxiety, especially of a cognitive nature, may have a large impact on improving quality of life. Am J Phys Med Rehabil, 2002 May, 81(5), 355 - 63 Botulinum toxin in upper limb spasticity after acquired brain injury: a randomized trial comparing dilution techniques; Francisco GE et al.; OBJECTIVE: To compare the efficacy of two different volume preparations of the same dose of botulinum toxin-A in relieving spasticity in wrist and finger flexors secondary to acquired brain injury . DESIGN: Thirteen adult patients who had modified Ashworth scale scores of 3 for both wrist and finger flexors were included in this randomized, controlled trial . Wrist and finger flexors were each injected . Blinded modified Ashworth scale ratings of wrist and finger flexor spasticity were measured . RESULTS: Spasticity in both muscles decreased significantly in both treatment groups . However, the high-volume and low-volume groups did not differ significantly in spasticity reduction . CONCLUSIONS: Because this preliminary study found no difference in spasticity reduction between high- and low-volume preparations of a 60-unit dose of botulinum toxin-A, a larger-sample study seems warranted to compare the efficacy of high-volume and low-volume preparations. Ann Readapt Med Phys, 2002 Apr, 45(4), 159 - 65 {Efficacy at six months of the botulinum toxin A in the post-stroke lower limb's muscular overactivity}; Yelnik A et al.; OBJECTIVE: Post-stroke hemiplegic patients are often disabled by a muscular overactivity of the lower limb which can be treated by botulinum toxin A (BTX) . The aim of this study was to assess the length of this efficiency as expressed by the patient . MATERIAL AND METHOD: The study was conducted among consecutive patients with post-stroke hemiplegia, disabled by a distal muscular overactivity of the lower limb . The injection of BTX (Botox Allergan) was given under electrostimulation guidance . Efficiency was assessed by the patient at 1, 3 and 6 months, by means of a three-point scale (absent, real but not enough, very good), on the basis of individual objectives previously defined after the precise description of the symptoms, their type of triggering and their functional impact . RESULTS: Fifty-seven sessions were conducted in 36 patients . At 1 month, 81% of the sessions were efficient, 39% with very good results . At 6 months, 57% of the sessions were still efficient with 25% of very good results . The best results were observed on the permanent extension of the great toe: the efficiency remained very good at 6 months for 47% of the sessions . CONCLUSION: Having been assessed by the patients on the basis of individual objectives, the good result of the treatment by BTX can persist for more than 6 months . This assessment is partly subjective but is, in clinical use, the main basis for the treatment discussion. Eur Arch Otorhinolaryngol, 2002 Jan, 259(1), 1 - 3 Botulinum toxin for dysphagia due to cricopharyngeal dysfunction; Moerman M et al.; Botulinum injection in the cricopharyngeal muscle has not yet been described thoroughly . In reviewing the literature, only 24 cases were found in which botulinum injection was used to treat cricopharyngeal dysfunction . We want to add another four cases and discuss specific indications and necessary pre-treatment examinations . Depending on the patient's history and the clinical findings, botulinum injection may be performed . Manometry and videofluoroscopy are not mandatory . The type of functional pathology defines whether botulinum toxin will be a definite treatment or a temporary relief. J Neurol, 2002 Jan, 249(1), 76 - 84 Efficacy of botulinum toxin A in upper limb function of hemiplegic patients; Rousseaux M et al.; Botulinum toxin A has been reported to reduce spasticity and increase the comfort of hemiplegic patients . The aim of this study was to assess the efficacy of the treatment on disability, especially in manual activities, and to attempt to identify predictive factors of improvement . Twenty patients (mean age: 54.4 years; M: 14; right hemiplegia: 12) were included, with a delay of at least three months after unilateral hemispheric stroke . Botulinum toxin A (BOTOX) was injected into the arm adductors (8 cases), forearm flexors (17 cases), pronators, wrist and finger flexors (20 cases),with a total dose of 200 to 300 U . Examination (day 1 and 15, month 2 and 5) consisted of spasticity assessment (modified Ashworth scale), muscle strength, passive range of motion (goniometry), and pain, followed by functional tests, especially the Rivermead Motor Assessment (RMA) and Nine-hole Peg Test (NHPT) . Performance in daily living was assessed with the Functional Independence Measure (FIM), and an original analysis of hand grasp, grip and pinches used in domestic activities (9 items), and of comfort of patients and caregivers . Significant reduction in spasticity was observed on the elbow flexors, pronators, wrist and fingers flexors, especially at day 15 (mean 0.90 to 1 point), with wide variations in effect . Muscle strength was increased in wrist and fingers extensors, with concomitant increase in the opening of the thumb to index finger space . There was no effect on the NHPT requiring distal manipulation, but the RMA, which especially concerned picking up and releasing a tennis ball, showed significant improvement . Furthermore, use of the upper limb in daily living increased, particularly for internal grasping of objects, and for grasping by the top, transporting and releasing of objects . Patients and caregivers re ported facilitation in dressing, and in proximal and distal care of the upper limb . The global flexor position of the limb improved . Ad verse reactions were rare and mostly consisted of transitory pain during injection . The improvement in the RMA was better explained by the quality of the initial motor command on distal prehension (positive correlation with motor strength), and that in hand using in domestic activities by a lower level of spasticity on pronators and wrist flexors (negative correlations with spasticity) . Conversely, the severity of the motor deficit (negative correlations with motor strength) and a high level of spasticity before injection (positive correlations with spasticity) mostly explained the improvement in comfort . In conclusion, botulinum toxin A is efficient in improving hand use in patients with relatively preserved distal motricity, and in increasing comfort in patients with severe global disorders. J Neurol, 2002 Jan, 249(1), 64 - 8 Comparison of preseptal and pretarsal injections of botulinum toxin in the treatment of blepharospasm and hemifacial spasm; Cakmur R et al.; Although the beneficial effect of subcutaneous injections of botulinum toxin type A (BTX-A) is well known in both blepharospasm and hemifacial spasm, the position of the injection sites around the orbicularis oculi may influence the effectiveness and side effects . Here we report results of preseptal and pretarsal BTX-A injections in 53 patients (25 blepharospasm and 28 hemifacial spasm) in whom we used both injection techniques successively . Pretarsal injections were used in 102 out of 186 treatments in blepharospasm group and in 84 out of 202 treatments in hemifacial spasm group . Pretarsal BTX-A treatment produced significantly higher response rate and longer duration of maximum response in both patient groups . This technique was also associated with a lower frequency of major side effects such asptosis . We concluded that injections of BTX-A into the pretarsal, rather than the preseptal portion of the orbicularis oculiis more effective for treatment of involuntary eyelid closure due to contractions of this muscle. J Neurol, 2002 Jan, 249(1), 57 - 63 A randomized, double-masked, crossover comparison of the efficacy and safety of botulinum toxin type A produced from the original bulk toxin source and current bulk toxin source for the treatment of cervical dystonia; Naumann M et al.; In 1997, the US FDA approved a new bulk toxin source (now referred to as current) for the manufacture of botulinum toxin type A (BTX-A) . The current BTX-A preparation has a lower neurotoxin complex protein load than the original BTX-A preparation, which may reduce antigenic potential . The present double-masked, multicenter study compared the efficacy and safety of BTX-A (BOTOX) produced from both original and current bulk toxin sources for the treatment of cervical dystonia . Patients (N = 133) were injected with BTX-A produced from original and current bulk toxin sources using a crossover design . Adverse events were assessed at each visit . Efficacy was assessed at 2 and 6 weeks post-injection using the severity and pain-disability subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) . Mean BTX-A doses were comparable (original: 155 U, current: 156 U) . Both BTX-A preparations produced similar, statistically significant reductions in TWSTRS severity and pain-disability scores at weeks 2 and 6 post-injection . The original and current BTX-A preparations showed no significant differences in adverse events, including both treatment-related (34%, 31%) and treatment-unrelated (27%, 32%), respectively . BTX-A produced from the original and current bulk toxin sources showed comparable efficacy and safety in the treatment of cervical dystonia; both significantly reduced dystonia severity and pain. Eur J Gastroenterol Hepatol, 2002 Mar, 14(3), 285 - 90 Achalasia treatment in the elderly: is botulinum toxin injection the best option? Zarate N, Mearin F, Baldovino F, Armengol JR, Malagelada JR. BACKGROUND : Achalasia treatment in elderly patients is a matter of controversy . Botulinum toxin injection has been proposed as the best option in this group of patients as it is a safe procedure . However, concern persists regarding its short-term effect . AIMS : To analyse the clinical and economic effectiveness of botulinum toxin injection in the treatment of achalasia patients who are elderly . METHODS : Seventeen consecutive achalasia patients older than 65 years were treated with 80 units of botulinum toxin . Clinical follow-up at 1, 6 and 12 months was performed . Control manometry when symptoms recurred was carried out . Results were compared with those of an historical control group of 16 achalasia patients also older than 65 years and who had been treated with endoscopic dilation . The costs of both procedures were compared . RESULTS : Twenty-nine botulinum toxin injections were performed in the 17 patients of the botulinum toxin group (follow-up, 12-36 months) . In the dilation group only two patients had to be retreated (follow-up, 12-108 months) . No major complications were observed in either group . The average duration of symptom alleviation was 48 +/- 33 months for endoscopic dilation and 13.8 +/- 9.5 months for botulinum toxin injection . Maintaining a patient free of symptoms cost E348.31 per year for botulinum toxin injection, whilst if endoscopic dilation was chosen the cost was only E117.47 per year . CONCLUSIONS : The effect of botulinum toxin injections wanes with time in elderly patients, necessitating repeated injections to keep the patients symptom-free . Due to the required repeated injections this procedure is more expensive than endoscopic dilation. Am J Phys Med Rehabil, 2002 Apr, 81(4), 272 - 8 Effect of intramuscular botulinum toxin injection on upper limb spasticity in stroke patients; Wang HC et al.; OBJECTIVE: To evaluate the therapeutic effect of intramuscular injection of botulinum toxin on spasticity of the upper limb, with emphasis on its influence over limb function . DESIGN: An open-label, noncontrolled trial with a duration of 12 wk was designed to determine the safety and efficacy of intramuscular botulinum toxin A injection in the treatment of 16 patients with stroke with spastic hemiparesis . Electromyographically guided intramuscular botulinum toxin A injections were applied to the spastic limbs . A detailed scale system was used for the evaluation of muscle tone and functional changes induced by botulinum toxin A treatment . RESULTS: No major side effect secondary to botulinum toxin A injection was reported . Statistically significant (P < 0.05) improvements of muscle tone, joint range of motion, hand muscle strength, and muscular pain were seen after the injection . The improvements lasted up to 8-12 wk after the treatment . However, there was no significant functional improvement except in two of the patients . CONCLUSIONS: Botulinum toxin A injection may help relieve upper limb spasticity and pain in patients with stroke . Its effect on function is probably determined by case selection. J Eur Acad Dermatol Venereol, 2002 Jan, 16(1), 40 - 2 Adjuvant botulinum toxin A in dyshidrotic hand eczema: a controlled prospective pilot study with left-right comparison; Wollina U et al.; OBJECTIVE: Dyshidrotic hand eczema is a therapeutic challenge . A prospective pilot study was performed with left-right comparison in order to investigate whether chemical de-innervation of sudoriferic nerves would be superior to standard therapy with topical corticosteroids . BACKGROUND: Botulinum toxin A (BTXA) is a potent inhibitor of acetylcholine release, that induces eccrine sweat production and release . Inhibition of sweating by other measures such as tap water iontophoresis has been shown to be beneficial in dyshidrotic hand eczema . METHODS: Eight adult patients suffering from dyshidrotic hand eczema (atopic type) were included in a prospective, side-by-side controlled clinical pilot study using topical corticosteroids on both hands in combination with intracutaneous injections of 100 units of BTXA (Botox) on the more severely affected hand on day 1 . The dyshidrotic hand eczema was classified using the DASI (Dyshidrotic Eczema Area and Severity Index) before treatment (0), after 1 week, 4 weeks and 8 weeks . RESULTS: Six patients completed the study, two dropped out because of social and personal reasons . The mean DASI score changed from 28 to17 with topical therapy alone and from 36 to 3 with adjuvant BTXA (P < 0.01) . Itching and vesiculation were inhibited earlier when using the combination of corticosteroids and BTXA . There was one relapse in the corticosteroid group . Relapses have not been seen in the BTXA group . CONCLUSIONS: Interruption of sweating by BTXA improves the outcome and reduces relapses in patients with dyshidrotic hand eczema . BTXA is antipruritic as well suggesting that it does not only interact with acetylcholine release but substance P. J Child Neurol, 2002 Feb, 17(2), 138 - 42 Open-label study of botulinum toxin for upper limb spasticity in cerebral palsy; Wong V et al.; The objective of this study was to assess the efficacy of botulinum toxin for upper limb spasticity in cerebral palsy . An open-label study was conducted in 11 children with cerebral palsy . Post-botulinum toxin assessment was conducted in weeks 1, 4, and 16, with averaged scores being analyzed . The Clinical Global Impression Scale of the mothers showed marked, moderate, and mild improvement in five, four, and two cases, respectively . The Modified Ashworth Spasticity Scale score showed a statistically significant decrease in the mean spasticity score (P < .003) . Other tests were performed depending on the cognition of the child . Increase in joint motion occurred in all five children assessed using web space (P = .043) . For the Jebson Hand Function Test, improvement occurred in all five cases assessed (P < .03) . Four of five (80%) children could perform tasks that they failed before they were given botulinum toxin . Botulinum toxin is useful in decreasing spasticity and improving the upper limb function of young children with cerebral palsy with normal cognition . Motivated families should be selected with a specific target of using botulinum toxin as an adjunct in a habilitation program. Harefuah, 2002 Mar, 141(3), 239 - 41, 315 {Clinical aspects and treatment of 95 patients with hemifacial spasm}; Badarny S et al.; Hemifacial Spasm (HFS) is considered a peripheral disease of the facial nerve caused by vascular compression at the nerve root in the pontocerebellar angle . We aimed to study the natural course of HFS and especially, to examine the relationships with psychological status or physical activities, in order to assess the possible role of the facial nucleus in the pathogenesis . Ninety-five consecutive patients with HFS, 52 men and 43 women, with a mean age of 62 + 12.7 years and a mean disease duration of 7.5 + 6.5 years, were personally interviewed by 2 of the authors (SB and HK) . A detailed questionnaire was completed with direct and indirect questions regarding the relationship between the severity of the spasms and emotional status or physical activity . We found strong association between emotional stress and tiredness and aggravation of the spasms in 85% and 54% of the patients, respectively . Talking increased the spasm severity in 58% of the patients and eating or drinking aggravated the spasm in 28% of the patients . Physical activity, head position, the season of the year or the time during the day had no effect on the clinical status . Botulinum toxin was injected to 78 patients with an overall subjective rate of improvement of > 70% in 74% of the patients (23% graded their rates of improvement as > 90%) . In conclusion, HFS is a movement disorder of the facial nerve which is highly influenced by emotional status to support an involvement of the facial nucleus in the pathogenesis . Botulinum toxin is a very effective long term treatment for this disorder. Artif Organs, 2002 Mar, 26(3), 263 - 6 A pilot study to investigate the combined use of botulinum neurotoxin type a and functional electrical stimulation, with physiotherapy, in the treatment of spastic dropped foot in subacute stroke; Johnson CA et al.; The objective was to inform sample size calculations for a full randomized controlled trial (RCT) . The design included an RCT pilot trial with a 16 week study period, including a 4 week baseline phase . The subjects were adults within 1 year of first stroke, ambulant with a spastic dropped foot . Twenty-one participants were recruited from the stroke services of 4 centers . For intervention all participants received physiotherapy; the treatment group also received botulinum neurotoxin Type A (BoNTA) intramuscular injections to triceps surae (800 U Dysport) and functional electrical stimulation (FES) of the common peroneal nerve to assist walking . The main outcome measure was walking speed . The result was a significant upward trend in median walking speed for both the control (p = 0.02) and treatment groups (nonstimulated p = 0.004, stimulated p = 0.042) . Trend lines were different in location (p = 0.04 and p = 0.009, respectively) . In conclusion, there is evidence of an additional, beneficial effect of BoNTA and FES . Sufficient information has been gained on the variability of the primary outcome measure to inform sample size calculations for a full RCT to quantify the treatment effect with precision. Arch Dermatol, 2002 Apr, 138(4), 510 - 4 Pain associated with injection of botulinum A exotoxin reconstituted using isotonic sodium chloride with and without preservative: a double-blind, randomized controlled trial; Alam M et al.; CONTEXT: Botulinum A exotoxin is used for various indications, including the treatment of dynamic forehead lines . OBJECTIVE: To determine whether injection with botulinum A exotoxin reconstituted with preservative-containing normal saline (isotonic sodium chloride) is less painful than injection with exotoxin that has been reconstituted with preservative-free saline . DESIGN: Two arms: (1) retrospective study; (2) double-blind, randomized controlled trial . SETTING: A multiple-physician dermatology practice . PATIENTS: (1) Retrospective study-20 consecutive adult patients presenting for treatment of upper-face dynamic lines; (2) prospective study-15 consecutive adult patients presenting for treatment of upper-face dynamic lines . INTERVENTION: In prospective study only, one side (left or right) of the face was treated with exotoxin reconstituted with preservative-containing saline, and the other side, with exotoxin reconstituted with preservative-free saline . MAIN OUTCOME MEASURES: (1) Retrospective study-discomfort at current treatment (with preservative-containing saline) compared with discomfort with most recent prior treatment (with preservative-free saline); (2) prospective study-discomfort on the side treated with preservative-containing saline compared with discomfort on the side treated with preservative-free saline . RESULTS: (1) Retrospective study-18 (90%) of 20 patients reported that treatment with exotoxin reconstituted with preserved saline was less painful than prior treatment with exotoxin reconstituted with preservative-free saline; (2) prospective study-15 (100%) of 15 patients reported less pain in the side of their face treated with exotoxin reconstituted with preservative-containing saline (P<.001) . Pain on the preservative-containing side was 54% less . No difference in treatment efficacy between the sides was observed by investigators or patients . CONCLUSION: Use of preservative-containing saline to reconstitute botulinum A exotoxin can significantly decrease patient discomfort on injection. Eur J Ophthalmol, 2002 Jan-Feb, 12(1), 55 - 9 Outcome of abducens nerve paralysis in patients with nasopharyngeal carcinoma; Ilhan O et al.; PURPOSE: The objective of this study was to investigate the incidence, management and outcome of patients with nasopharyngeal carcinoma (NPC) who developed Vlth nerve palsy . METHODS: Between December 1993 and December 1999, we investigated retrospectively the charts of 166 patients with NPC . RESULTS: Twenty-eight of 166 patients (16.8%) had cranial nerve involvement at the time of the diagnosis of NPC . Sixteen (57.2%) were identified as having abducens nerve palsy . In 25% abducens nerve palsy was the presenting symptom . Three patients were able to compensate for their diplopia after prism correction or botulinum toxin-A injection, and six (50%) completely recovered from abducens nerve palsy after either radiotherapy or chemotherapy . CONCLUSIONS: Abducens is the most common cranial nerve involved in NPC, radiotherapy and or chemotherapy relieves the paralysis in half the patients . Prism correction or botulinum toxin-A injection are effective non-invasive procedures for patients with significant diplopia. Traffic, 2002 Apr, 3(4), 298 - 307 Calcium-dependent transferrin receptor recycling in bovine chromaffin cells; Knight DE; The release of regulated secretory granules is known to be calcium dependent . To examine the Ca2+-dependence of other exocytic fusion events, transferrin recycling in bovine chromaffin cells was examined . Internalised 125I-transferrin was released constitutively from cells with a half-time of about 7 min . Secretagogues that triggered catecholamine secretion doubled the rate of 125I-transferrin release, the time courses of the two triggered secretory responses being similar . The triggered 125I-transferrin release came from recycling endosomes rather than from sorting endosomes or a triggered secretory vesicle pool . Triggered 125I-transferrin release, like catecholamine secretion from the same cells, was calcium dependent but the affinities for calcium were very different . The extracellular calcium concentrations that gave rise to half-maximal evoked secretion were 0.1 mm for 125I-transferrin and 1.0 mm for catecholamine, and the intracellular concentrations were 0.1 microm and 1 microm, respectively . There was significant 125I-transferrin recycling in the virtual absence of intracellular Ca2+, but the rate increased when Ca2+ was raised above 1 nm, and peaked at 1 microm when the rate had doubled . Botulinum toxin type D blocked both transferrin recycling and catecholamine secretion . These results indicate that a major component of the vesicular transport required for the constitutive recycling of transferrin in quiescent cells is calcium dependent and thus under physiological control, and also that some of the molecular machinery involved in transferrin recycling/fusion processes is shared with that for triggered neurosecretion. Dig Liver Dis, 2002 Feb, 34(2), 105 - 10 Long-term follow-up of achalasia patients treated with botulinum toxin; D'Onofrio V et al.; AIMS: To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief MATERIALS AND METHODS: A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin . Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin . In the case of failure or relapse (symptom score >2), treatment was repeated . RESULTS: All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin . At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal) . Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment . Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30) . Up to day 31 (83.7%) patients were still in remission . We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053) . Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5) CONCLUSIONS: Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief. J Biol Chem, 2002 Jun 7, 277(23), 20195 - 204 Epub 2002 Mar 29. The 25-kDa synaptosome-associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells; Ji J et al.; Delayed-rectifier K(+) channels (K(DR)) are important regulators of membrane excitability in neurons and neuroendocrine cells . Opening of these voltage-dependent K(+) channels results in membrane repolarization, leading to the closure of the Ca(2+) channels and cessation of insulin secretion in neuroendocrine islet beta cells . Using patch clamp techniques, we have demonstrated that the activity of the K(DR) channel subtype, K(V)1.1, identified by its specific blocker dendrodotoxin-K, is inhibited by SNAP-25 in insulinoma HIT-T15 beta cells . A co-precipitation study of rat brain confirmed that SNAP-25 interacts with the K(V)1.1 protein . Cleavage of SNAP-25 by expression of botulinum neurotoxin A in HIT-T15 cells relieved this SNAP-25-mediated inhibition of K(DR) . This inhibitory effect of SNAP-25 is mediated by the N terminus of K(V)1.1, likely by direct interactions with K(Valpha)1.1 and/or K(V)beta subunits, as revealed by co-immunoprecipitation performed in the Xenopus oocyte expression system and in vitro binding . Taken together we have concluded that SNAP-25 mediates secretion not only through its participation in the exocytotic SNARE complex but also by regulating membrane potential and calcium entry through its interaction with K(DR) channels. Eur J Neurol, 2002 May, 9 Suppl 1, 48 - 52; dicussion 53-61 A summary of spasticity management--a treatment algorithm; Ward AB; The muscle overactivity seen in spasticity results in limb stiffness and muscle spasm, to which there is both a neurogenic and a biomechanical component . Spasticity does not always cause harm and can assist in the rehabilitation process enabling a patient to stand when their limb weakness would not otherwise allow it . When it does cause harm, however, treatment is required . This aims to (i) prevent provocative factors (ii) treat muscle overactivity; and (iii) prevent complications . Untreated, limb contracture, pain and other complications occur and early management can be most effective . Treatment is essentially physical, but, when this is inadequate, pharmacological intervention may be required . A strategy has been devised which shows that the first choice pharmacological treatment of focal spasticity is botulinum toxin . Over the past decade, the choice of treatment has become more ambitious with the establishment of new technologies . Good management now depends on an understanding of their role and application in relation to the needs of individual patients . To this end, a treatment algorithm which covers the salient facts in patient assessment and gives the indications for the range of available treatments, is the best approach . The indications and limitations of the available treatments are discussed, along with their place in the overall management of the patients . The evidence base for much of what is done is not strong and this summary examines the activities of proven value and of consensus view. Eur J Neurol, 2002 May, 9 Suppl 1, 42 - 7; dicussion 53-61 Botulinum toxin A (BoNT-A) for spasticity in adults . What is the evidence? Moore AP. There are now many reports from open, uncontrolled studies which suggest that botulinum toxin A (BoNT-A) is valuable in treating spasticity . Evidence of its benefit is also gradually accumulating from randomized controlled trials (RCTs) . In this presentation I will discuss the reasons why RCT evidence is being generated, and describe the findings currently available, including preliminary results from as yet unpublished trials . RCT data have been reported for leg and arm spasticity in a variety of diseases, but predominantly in stroke and multiple sclerosis patients . In most RCTs, the effects of BoNT-A are compared with placebo over a single injection cycle . The outcomes are generally positive and support the use of BoNT-A . However, data from RCTs are less convincing than those from open studies for a variety of technical reasons . These especially reflect the difficulties of finding good outcome measures for such a heterogeneous array of patients . There is good evidence that BoNT-A has clinical benefit in treating the mechanical effects of spasticity . In order to further clarify its usefulness, future research should address the strategies of short- and longer-term use of BoNT-A, and the unresolved technical issues of how to get the best out of this new treatment. Eur J Neurol, 2002 May, 9 Suppl 1, 23 - 9; dicussion 53-61 Gait training in hemiplegia; Mauritz KH; Restoration of gait is a major goal in neurological rehabilitation . Before starting therapy, a comprehensive assessment is necessary to evaluate the deficits and remaining functions . A wide variety of therapeutic procedures are available and have to be adapted to the individual situation - different concepts of physiotherapy stress different features like: force exercise, reduction of spasticity, gait symmetry, utilization of equilibrium reflexes, stepping automation, endurance training, repetition of rhythmic movements, etc . The spectrum of available therapies was recently widened by treadmill training, with partial body-weight support, locomotor pharmacotherapy, selective reduction of spasticity by botulinum toxin injections, and by musical biofeedback, which have each proved to be successful in the restoration of gait pattern . Treadmill training based on partial body weight support, combined with enforced stepping movements has proved to be successful in the restoration of gait pattern . A common problem in hemiparetic gait, is the spastic inversion of the foot . If spasticity is not severe, an ankle-foot orthosis (AFO) is the appropriate technical aid . In other cases, botulinum toxin injection into spastic leg muscles has been successfully used to improve gait functions . In hemiparetic stroke patients, auditory (musical) rhythm, as a peripheral pacing signal, resulted in a significant increase in weight-bearing stance time on the paretic side . In addition, there was an improved stride symmetry with rhythmic cueing and a normalizations of gait pattern . These methods directed to gait improvement should be combined and adapted to the individual patient's needs, in order to obtain the best results. Gastroenterology, 2002 Apr, 122(4), 994 - 1006 SNAP-25, a SNARE protein, inhibits two types of K channels in esophageal smooth muscle; Ji J et al.; BACKGROUND & AIMS: The plasma membrane-associated soluble N-ethylmaleimide-sensitive factors attachment protein receptors (SNAREs), synaptosome-associated protein of 25 kilodaltons (SNAP-25), and syntaxin 1A, have been found to physically interact with and functionally modify membrane-spanning ion channels . Studies were performed in cat esophageal body and lower esophageal sphincter (LES) smooth muscle to (1) show the presence of SNAP-25, and (2) determine whether SNAP-25 affects K+ channel activity . METHODS: Single circular muscle cells from the esophageal body and sphincter were studied . Cellular localization of SNAP-25 and K+ channel activity were assessed . RESULTS: SNAP-25 was found in the plasma membrane of all regions examined . Outward K+ currents in body circular muscle were mainly composed of large conductance Ca2+-activated channel currents (K(Ca), 40.1%) and delayed rectifier K+ channel currents (K(V), 54.2%) . Microinjection of SNAP-25 into muscle cells caused a dose-dependent inhibition of both outward K+ currents, maximal 44% at 10(-8) mol/L . Cleavage of endogenous SNAP-25 by dialyzing botulinum neurotoxin A into the cell interior resulted in a 35% increase in outward currents . CONCLUSIONS: SNAP-25 protein is present in esophageal smooth muscle cells, and inhibits both K(V) and K(Ca) currents in circular muscle cells . The findings suggest a role for SNAP-25 in regulation of esophageal muscle cell excitability and contractility, and point to potential new targets for treatment of esophageal motor disorders. J Neurol Neurosurg Psychiatry, 2002 Apr, 72(4), 459 - 62 Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia; Ranoux D et al.; OBJECTIVES: Botulinum toxin type A is a potent neuromuscular paralyzing agent used in various disorders including cervical dystonia . Two preparations of botulinum toxin are now commercially available ( Dysport and Botox), but much controversy remains about their respective potencies . The aim of the study was to compare the efficacy of Botox with two different ratios of Dysport . METHODS: A double blind, randomised, three period cross over study involving 54 patients with cervical dystonia was performed . The patients received the following treatments in a randomised order: Botox at the usually effective dose, Dysport at a dose of 1:3 (conversion factor of 3 between Botox and Dysport units-that is, one Botox unit=three Dysport units) and at a dose of 1:4 (conversion factor of four) . The improvement of the Tsui (primary outcome criteria) and of the TWSTRS pain scales between baseline and a control visit 1 month after each of the three injections, as well as the incidence of adverse events, were assessed . RESULTS: Comparison of the Tsui scores and of the TWSTRS pain scores showed a better effect on impairment and pain with Dysport 1:3 (p=0.02 and 0.04, respectively) and 1:4 (p=0.01 and 0.02, respectively) than with Botox . The number of adverse events was higher with both Dysport treatments . The most frequent adverse event was dysphagia, found in 3%, 15.6%, and 17.3% (Botox, Dysport 1:3 and 1:4, respectively) of the patients . No adverse event required withdrawal of therapy or specific management . CONCLUSIONS: Dysport 1:3 (and Dysport 1:4 to a greater extent) is more efficient than Botox for both impairment and pain in cervical dystonia although with a somewhat higher incidence of minor adverse effects . This strongly suggests that the most appropriate conversion factor between Botox and Dysport units is less than 3 in cervical dystonia. J Am Acad Dermatol, 2002 Apr, 46(4), 617 - 9 Botulinum toxin type A injection in the treatment of lichen simplex: an open pilot study; Heckmann M et al.; Recalcitrant pruritus is a hallmark of lichen simplex, a localized variant of atopic dermatitis . Acetylcholine has been demonstrated to mediate pruritus in atopic dermatitis . This open pilot study was done to determine the therapeutic effect of blocking acetylcholine release with botulinum toxin A in highly pruritic lichen simplex . Botulinum toxin A (Dysport) was injected intradermally into 5 circumscribed lichenoid lesions in 3 patients suffering from recalcitrant pruritus . No corticosteroids or any other specific topical therapy was administered . Pruritus subsided within 3 to 7 days in all 3 patients . Within 2 to 4 weeks all lesions cleared completely . No recurrences were noted over a 4-month follow-up . In one patient lichen simplex developed on the contralateral shin, which responded equally to a subsequent injection . We concluded that lichen simplex-associated pruritus can be overcome by intradermal botulinum toxin A injection . Acetylcholine appears to be a dominant pruritic mediator in this condition. J Am Acad Dermatol, 2002 Apr, 46(4), 536 - 40 High-dose botulinum toxin type A therapy for axillary hyperhidrosis markedly prolongs the relapse-free interval; Wollina U et al.; BACKGROUND: Axillary hyperhidrosis is a common condition that can be personally distressing and can interfere with professional and social life . Intracutaneous injections of botulinum toxin type A (BTXA) have recently been shown to induce an effective but temporary anhidrosis, usually for 4 to 6 months . High-dose BTXA was shown to have a lower relapse rate, but it remained unclear whether it could induce a prolongation of the antihidrotic effect . OBJECTIVE: Our aim was to evaluate the long-term effectiveness of "high-dose" botulinum toxin therapy in axillary hyperhidrosis, the response to repeated treatment, and the possible side effects . METHODS: In an open study in a university medical center, 47 patients with axillary hyperhidrosis unresponsive to previous therapies were treated with intracutaneous injections of botulinum A toxin . A total dose of 200 U of BTXA was used per axilla . Patients were followed up for periods up to 29 months . The main outcome measures were patients' satisfaction with the antihidrotic effect, response to repeated treatment, and safety of treatment . RESULTS: Within 6 days of the injection of BTXA, all patients reported cessation of excessive sweating . The follow-up was 17.0 +/- 8.3 months (range, 3-29 months) . The relapse rate within 12 months of treatment was 4 of 34 patients (11.8%) . The longest relapse-free interval observed was 29 months . Twenty-two patients showed a relapse-free interval of 19 months or more . The number of patients with at least 12 months of remission was significantly higher with 200 U of botulinum toxin than with lower doses reported in current literature (P <.05) . Relapsed patients (a total of 6/47) showed an unchanged excellent response to a second or third treatment . The only side effect was temporary pain and burning during the injections . No muscular weakness, insensitivity, or systemic reactions were observed . CONCLUSION: High-dose BTXA treatment is capable of prolonging the antihidrotic effect of intracutaneous BTXA in most patients for more than 19 months . It reduces the percentage of relapses after 12 months of follow-up to less than 12% . So far, there is no clinical evidence of the induction of neutralizing antibodies . High-dose treatment seems to be as safe as low-dose treatment. FEBS Lett, 2002 Feb 27, 513(2-3), 163 - 8 Development of a delivery vehicle for intracellular transport of botulinum neurotoxin antagonists; Goodnough MC et al.; A targeted delivery vehicle (DV) was developed for intracellular transport of emerging botulinum neurotoxin (BoNT) antagonists . The DV consisted of the isolated heavy chain (HC) of BoNT/A coupled to a 10-kDa amino dextran via the heterobifunctional linker 3-(2-pyridylthio)-propionyl hydrazide . The HC served to target BoNT-sensitive cells and promote internalization of the complex, while the dextran served as a platform to deliver model therapeutic molecules to the targeted cells . To determine the ability of this chimeric glycoprotein to enter neurons, dextran and HC were labeled independently with the fluorescent dyes Oregon green 488 and Cy3, respectively . Internalization of DV was monitored in primary cortical cells using laser confocal microscopy . Incubation of cells for 24 h with DV resulted in discrete punctate labeling of both soma and processes . The Cy3 and Oregon green 488 signals were generally co-localized, suggesting that the complex remained in the same intracellular compartment during the initial 24 h . The DV-associated fluorescence was reduced progressively by co-application of increasing concentrations of unlabeled BoNT/A holotoxin . The results suggest that the BoNT/A HC is able to mediate internalization of a coupled dextran, even though the latter bears no resemblance to the BoNT/A light chain (LC) . The HC of BoNT/A thus offers promise as a selective carrier to deliver BoNT antagonists to the nerve terminal cytoplasm for inhibiting the proteolytic activity of internalized BoNT/A LC. Headache, 2001 Nov-Dec, 41(10), 985 - 9 Botulinum toxin type A and EMG: a key to the understanding of chronic tension-type headaches? Rollnik JD, Karst M, Fink M, Dengler R. BACKGROUND: The pathogenesis of chronic tension-type headache remains unclear, and the role of muscle tension is especially controversial . Botulinum toxin type A, a potent inhibitor of muscle tone, has been used to treat chronic tension-type headache . OBJECTIVE: To determine whether clinical response to treatment of chronic tension-type headache with Botox A parallels changes in resting muscle activity recorded through serial electromyography (EMG) . METHODS: We randomly assigned eight patients with chronic tension-type headache to pericranial injection of 500 MU Botox A versus placebo (isotonic saline) . RESULTS: At 6 and 12 weeks following treatment, there were no significant differences in clinical outcome between the placebo and the Botox A groups . This occurred despite EMG evidence of a reduction in resting muscle activity in the Botox A-treated patients . CONCLUSION: These results support the hypothesis that peripheral mechanisms such as increased muscle tone play, at most, a minor role in the pathophysiology of chronic tension-type headache. Ophthalmologica, 2002 Jan-Feb, 216(1), 50 - 4 Effect of botulinum toxin A on facial wrinkle lines in Koreans; Lew H et al.; Two kinds of botulinum toxin type A were clinically evaluated in rhytidectomy . Twenty Korean patients with facial wrinkles were fully assessed following treatments with random injections . The mean degree of wrinkles before the injections was 2.83 and the mean corrective effect was 70.0% at least 3 months afterward . The effect lasted less than 6 months in only 9 cases . The complications were tingling sensations in 3 cases (15.0%), temporary lid swelling in 5 cases (25.0%) and lagophthalmos in 3 cases (15.0%) . No serious or permanent adverse effects were observed . Botulinum toxin type A rhytidectomy was a very effective method of removing various facial wrinkles although the treatment for complications and side effects will need to be considered . Curr Neurol Neurosci Rep, 2001 Jul, 1(4), 350 - 6 Neurologic disorders of gait; Sudarsky L; Gait disorders are important because of their prevalence, particularly among the elderly, and the associated risk of falls and injury . Neural networks that organize locomotion and maintain balance are briefly reviewed . Gait disorders can be classified based on observational features or by etiology . Several common disorders are discussed in more detail . Recent progress includes use of botulinum toxin for spastic gait in cerebral palsy, neurosurgical treatment of Parkinson's disease, and newer rehabilitation approaches to gait and balance training. Curr Neurol Neurosci Rep, 2001 Jul, 1(4), 337 - 45 Focal dystonia: the role of botulinum toxin; Tintner R et al.; Botulinum toxin (BTX) has been found to be effective in a wide range of focal dystonias . Debate surrounds the selection of injection sites . In general, localization is satisfactory by clinical examination, but poor response, requiring localization of deep muscles, may necessitate use of electromyography for localization . Delineation of optimal doses of BTX is a work in progress; as studies have tended to show efficacy at lower doses than used in the past, the trend is to use lower doses . This is important, because development of antibodies to BTX, the main reason for secondary resistance to this treatment, is more frequent with larger doses and shorter inter-injection intervals . Although the mechanism of denervation of the neuromuscular injunction by BTX is relatively well understood, secondary changes at the level of the basal ganglia, thalamus, and cortex, and their role in response to BTX, need further exploration. Curr Neurol Neurosci Rep, 2001 Mar, 1(2), 195 - 202 The treatment of tics; Singer HS; Tics are the essential component of a variety of disorders, notably Tourette syndrome . Because the mere presence of tics does not require therapeutic intervention, criteria are essential for determining a functional disability . Suggested tic-suppressing treatments have been extremely diverse, including hydrotherapy, behavioral treatments, pharmacotherapy, botulinum toxin, immunomodulatory therapy, and surgery . This manuscript reviews each of these approaches with emphasis on more recent pharmacologic trials. Am J Ther, 2002 Mar-Apr, 9(2), 157 - 61 Treatment of achalasia with botulinum A toxin; da Silveira EB et al.; Achalasia is an idiopathic neuromuscular disorder of the esophagus which is associated with absence of esophageal peristalsis and incomplete relaxation of a normal or raised lower esophageal sphincter (LES) . Dysphagia is the most commonly associated symptom . Conventional therapeutic approaches are directed to reducing LES pressure and include orally-administered smooth muscle relaxants, forceful sphincter dilation with balloon dilators, and open or laparoscopic-assisted myotomy of the LES . Pharmacologic therapies have a low success rate . Forceful dilation has a perforation complication rate of 2% to 5%, and myotomies may precipitate significant gastroesophageal reflux, a complication minimized when a partial fundal wrap is employed simultaneously . In recent years, botulinum toxin, utilized widely as a striated muscle relaxant in managing blepharospasm, anal sphincter spasm, and muscle spasm complicating CVAs, and in smoothening facial wrinkles, has been extended to the management of achalasia on the basis that it impairs smooth muscle responsiveness to acetylcholine . Eighty units of Botox (botulinum toxin) are injected directly into the endoscopically (endoscopic ultrasound techniques may facilitate localization) located LES region (20 units into each of 4 quadrants) . Symptom relief lasting 6 months on average is experienced in more than 65% of treated patients, and the complication rate is negligible . This therapeutic option is reserved for patients too ill to undergo any surgical procedure and is most effective when the lower esophageal region is hypertonic. Dermatol Surg, 2002 Mar, 28(3), 257 - 62 The corset platysma repair: a technique revisited; Jacob CI et al.; BACKGROUND: Platysma banding along with excess submental adipose tissue and sagging skin can lead to an aged appearance . Several methods for improving neck and submental contours exist, including neck liposuction, bilateral platysma plication, midline platysma plication with transection of distal fibers, necklift with skin excision, and botulinum toxin injection for platysma relaxation . With the current interest in minimally invasive procedures, surgeons and patients are searching for techniques that produce maximal improvement with minimal intervention . OBJECTIVE: To present a modified technique for maximizing neck contouring, discuss possible complications of the procedure, and describe appropriate candidates for the corset platysmaplasty . METHODS: We performed a retrospective analysis of 10 consecutive patients who underwent neck liposuction with concomitant corset platysmaplasty at our institution . RESULTS: All 10 patients achieved good to excellent submental and jawline contouring, determined by both physician and patient assessment, with no visible platysma banding at 6 months follow-up . No major complications were noted . CONCLUSION: Use of corset platysmaplasty is a safe and effective method for neck rejuvenation . This variation of platysmaplasty can be used in conjunction with neck liposuction to maximize jawline and neck contour enhancement. Lakartidningen, 2002 Feb 21, 99(8), 786 - 9 {Living with dystonia . A questionnaire study among members of the Swedish Dystonia Patient Association}; Silfors A et al.; The dystonias are movement disorders with sustained muscle contractions causing twisting movements or abnormal postures . A patient survey sent to 268 members of the Swedish Dystonia Patient Association was returned by 221 (82%) . Most of the patients (81%) were women and the most common form was cervical dystonia (spasmodic torticollis) . Median age at onset was 41.6 years . The time from onset of symptoms to correct diagnosis was on average 6 years . 21% had relatives with movement derangements . Injection with Botulinum toxin and physical therapy were ranked as the most effective treatments . Many patients expressed a need for more physical therapy as well as a desire to meet the same physician each time and to receive more intensive psychological support. Compr Ther, 2002 Spring, 28(1), 15 - 22 Achalasia: a review of therapeutic options and outcomes; Da Silveira EB et al.; Advances in achalasia has led to the development of new therapeutic options . This review will focus on methodology and outcomes of two established techniques; pneumatic dilation and surgical myotomy; and one new technique, LES injection of botulinum A toxin. Arch Neurol, 2002 Mar, 59(3), 418 - 20 Botulinum toxin A treatment for primary hemifacial spasm: a 10-year multicenter study; Defazio G et al.; BACKGROUND: Botulinum toxin A (BTX) is the currently preferred symptomatic treatment for primary hemifacial spasm (HFS), but its long-term efficacy and safety are not known . OBJECTIVE: To assess the long-term effectiveness and safety of BTX in the treatment of primary HFS . DESIGN: Retrospective review of medical records of the 1st and 10th years of treatment . SETTING: Outpatient clinics of 4 Italian university centers in the Italian Movement Disorders Study Group . PARTICIPANTS: A series of 65 patients with primary HFS who had received BTX injections regularly for at least 10 years . MAIN OUTCOME MEASURES: Mean duration of improvement and quality of the effect induced by the preceding treatment (measured using a patient self-evaluation scale) and occurrence and duration of adverse effects in the 1st and 10th years of treatment . RESULTS: Using a mean BTX dose per treatment session similar to that used by others, we obtained a 95% response rate and an overall mean duration of improvement of 12.6 weeks during year 1 . The effectiveness of BTX in relieving the symptoms of primary HFS, as measured by the response rate and average duration of improvement, remained unchanged in the 1st and 10th years . Patients needed statistically similar BTX doses in the 1st and 10th years . The rate of local adverse effects (including upper lid ptosis, facial weakness, and diplopia) diminished significantly in the 10th year of treatment . CONCLUSION: Treatment with BTX effectively induces sustained relief from symptoms of HFS in the long term, with only minimal and transient adverse reactions. Laryngoscope, 2002 Feb, 112(2), 220 - 3 Risk factors and demographics in patients with spasmodic dysphonia; Schweinfurth JM et al.; OBJECTIVES: Spasmodic dysphonia has been characterized as a functional, psychogenic, or movement disorder with no known etiology or cure . In the present study, risk factors associated with other movement disorders were evaluated in patients with spasmodic dysphonia . STUDY DESIGN: Retrospective patient survey of 168 patients with a known diagnosis of spasmodic dysphonia who completed questionnaires at the time of interval botulinum toxin injection . METHODS: Patients completed questionnaires on demographics, education level, work history, significant life events, medical, social, and family history . The results were compared with those of first-degree relatives as a control group with similar demographics . Data were analyzed using percentages calculated on the total number of responses and distribution of frequency of each . Statistical significance was estimated on t tests of chi2 values . RESULTS: In the series of 168 patients, there was a female predominance of 79% . Age range at onset was 13 to 71 years with an average of age of 45 years . Sixty-five percent of patients had previously had the measles or mumps compared with the national average of 15% in a similar age group (P =.0001) . Thirty percent of patients directly associated onset of spasmodic dysphonia symptoms to an upper respiratory tract infection, and 21% to a major life stress . There was no significant incidence of any other medical or neurological condition or symptomatology . There was no family history of spasmodic dysphonia . Twenty-six percent of patients had an essential tremor compared with 4% of first-degree relatives (P =.0001), and 11% had associated writer's cramp compared with 2% of relatives (P =.02) . Less than 1% of patients described a history of toxic exposure or electrical injury . CONCLUSIONS: The majority of patients with spasmodic dysphonia are girls and women . A significantly higher incidence of childhood viral illness was found in the patients with spasmodic dysphonia . Patients with spasmodic dysphonia had a significant incidence of both essential tremor and writer's cramp but no history of major illness or other neurological disorder . There appear to be no significant environmental or hereditary patterns in the etiology of spasmodic dysphonia . Stress or viral infection may induce the onset of symptoms of spasmodic dysphonia . Many features of the disorder are common to other movement disorders, and this knowledge may direct future research efforts. Neurology, 2002 Mar 12, 58(5), 805 - 7 Accuracy of muscle localization without EMG: implications for treatment of limb dystonia; Molloy FM et al.; Although botulinum toxin is an effective treatment for focal dystonia, the importance of electromyography (EMG) in identifying muscles and guiding injections is unclear . The authors examined the accuracy of muscle localization in 38 muscles in patients with focal hand dystonia without EMG guidance . Only 37% of needle placement attempts reached the target muscles or muscle fascicles . This study demonstrates that EMG guidance is needed for correct localization of desired muscles. Dev Biol, 2002 Mar 15, 243(2), 326 - 38 SNARE complex assembly is required for human sperm acrosome reaction; Tomes CN et al.; Exocytosis of the acrosome (the acrosome reaction) is a terminal morphological alteration that sperm must undergo prior to penetration of the extracellular coat of the egg . Ca(2+) is an essential mediator of this regulated secretory event . Aided by a streptolysin-O permeabilization protocol developed in our laboratory, we have previously demonstrated requirements for Rab3A, NSF, and synaptotagmin VI in the human sperm acrosome reaction . Interestingly, Rab3A elicits an exocytotic response of comparable magnitude to that of Ca(2+) . Here, we report a direct role for the SNARE complex in the acrosome reaction . First, the presence of SNARE proteins is demonstrated by Western blot . Second, the Ca(2+)-triggered acrosome reaction is inhibited by botulinum neurotoxins BoNT/A, -E, -C, and -F . Third, antibody inhibition studies show a requirement for SNAP-25, SNAP-23, syntaxins 1A, 1B, 4, and 6, and VAMP 2 . Fourth, addition of bacterially expressed SNAP-25 and SNAP-23 abolishes exocytosis . Acrosome reaction elicited by Rab3-GTP is also inhibited by BoNT/A, -C, and -F . Taken together, these results demonstrate a requirement for members of all SNARE protein families in the Ca(2+)- and Rab3A-triggered acrosome reaction . Furthermore, they indicate that the onset of sperm exocytosis relies on the functional assembly of SNARE complexes . (C)2002 Elsevier Science (USA). Urology, 2002 Mar, 59(3), 325 - 7; discussion 327-8 Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results; Schulte-Baukloh H et al.; OBJECTIVES: The established treatment of children with neurogenic bladder consists of the use of anticholinergic drugs, such as oxybutynin and tolterodine, and clean intermittent catheterization four or five times a day . If anticholinergic drugs and clean intermittent catheterization fail, surgery is often necessary . With the intent of avoiding surgery, we investigated the effect of botulinum-A toxin for treating detrusor hyperreflexia in this group of patients . METHODS: The subjects were 17 children (average age 10.8 years) who had detrusor hyperreflexia and were using clean intermittent catheterization four or five times a day . Urodynamic studies were followed by injection of 85 to 300 U of botulinum-A toxin into 30 to 40 sites in the detrusor muscle . Urodynamic follow-up was done 2 to 4 weeks after injection . RESULTS: The mean reflex volume increased by 112.1%, from 95.00 plus minus 34.54 mL (range 47 to 147) to 201.45 plus minus 68.57 mL (range 77 to 310) (P <0.005) . The maximal bladder capacity increased by 56.5%, from 137.53 plus minus 59.96 mL (range 59 to 242) to 215.25 plus minus 96.36 mL (range 60 to 380) (P <0.005) . The maximal detrusor pressure decreased by 32.6%, from 58.94 plus minus 32.32 cm H(2)O (range 19 to 149) to 39.75 plus minus 26.12 cm H(2)O (range 7 to 100) (P <0.005) . Detrusor compliance increased by 121.6%, from 20.39 plus minus 26.5 mL/cm H(2)O (range 4.5 to 40) to 45.18 plus minus 45.4 mL/cm H(2)O (range 5.3 to 100) (P <0.01) . CONCLUSIONS: Botulinum-A toxin injection into the hyperreflexive detrusor muscle seems to be very effective and might be a therapeutic alternative to anticholinergic drugs. Dis Esophagus, 2001, 14(3-4), 227 - 31 Randomized controlled trial of intrasphincteric botulinum toxin A injection versus balloon dilatation in treatment of achalasia cardia; Ghoshal UC et al.; As the few randomized controlled trials available in the literature comparing botulinum toxin (BT) injection with established endoscopic treatment of achalasia cardia, i.e . pneumatic dilatation, showed conflicting results, we conducted a prospective randomized trial . Seventeen consecutive patients with achalasia cardia diagnosed during a period between December 1997 and February 2000 were randomized into two treatment groups {pneumatic dilatation by Rigiflex dilator (n=10), BT injection by sclerotherapy needle into four quadrants of lower esophageal sphincter (LES) (n=7) 80 units in five cases, 60 units in two cases} after dysphagia grading, endoscopy, barium esophagogram, and manometry, all of which were repeated 1 week after treatment . Patients were followed up clinically for 35.2+/-14 weeks . Chi-squares, Wilcoxon rank-sum test, Kaplan-Meier method and log-rank tests were used for statistical analysis . After 1 week, 6/7 (86%) BT-treated vs . 8/10 (80%) dilatation-treated patients improved (P=NS) . There was no difference in LES pressure and maximum esophageal diameter in the barium esophagogram in the two groups before therapy . Both therapies resulted in significant reduction in LES pressure . The cumulative dysphagia-free state using the Kaplan-Meier method decreased progressively in BT-treated compared with dilatation-treated patients (P=0.027) . Two patients with tortuous megaesophagus, one of whom had failed dilatation complicated by perforation previously, improved after BT . One other patient in whom pneumatic dilatation had previously failed improved in a similar manner . BT is as good as pneumatic dilatation in achieving an initial improvement in dysphagia of achalasia cardia . It is also effective in patients with tortuous megaesophagus and previous failed pneumatic dilatation . However, dysphagia often recurs during 1-year follow up. Neurology, 2002 Feb 26, 58(4), 649 - 52 Not paralysis, but dystonia causes stridor in multiple system atrophy; Merlo IM et al.; Electromyography (EMG) was performed in 10 patients with multiple system atrophy, laryngeal or pharyngeal symptoms, or both . In patients with stridor, EMG during quiet breathing revealed persistent tonic activity in both abductor and adductor vocal cord muscles . In patients with dysphagia, the cricopharyngeal muscle showed persistent EMG activity throughout all phases of swallowing . Botulinum toxin injection into the adductor muscle determined subjective improvement and reduced tonic EMG activity . Therefore, the cause of stridor in multiple system atrophy is dystonia of the vocal cords. J Cell Sci, 2002 Feb 1, 115(Pt 3), 667 - 73 Multiple forms of SNARE complexes in exocytosis from chromaffin cells: effects of Ca(2+), MgATP and botulinum toxin type A; Lawrence GW et al.; The changes that SNAREs undergo during exocytosis were studied in permeabilised chromaffin cells treated with Ca(2+), MgATP or botulinum neurotoxin A . High-resolution 2D SDS-PAGE revealed multiple SDS-resistant SNARE complexes having a wide range of sizes and in which SNAP-25 and syntaxin predominate over synaptobrevin . Their formation increased upon Ca(2+)-stimulated exocytosis; notably, the 2D protocol proved much superior to 1D SDS-PAGE for the detection of large complexes and revealed that for forms with relative molecular mass greater than 100,000 stimulated induction was more significant than for smaller species . MgATP enhanced Ca(2+)-triggered catecholamine release but reduced the content of complexes . By contrast, botulinum neurotoxin type A inhibited exocytosis and altered the stoichiometry of the SNAP-25:syntaxin binary association, without lowering its abundance . The individual SNAREs were protected against trypsin proteolysis to varying extents in binary and ternary complexes of different sizes, suggestive of distinct folding intermediates . Our data suggest that Ca(2+) triggers an early stage of SNARE complex formation causing an accumulation of partially folded intermediates, especially of binary forms, as well as their maturation into smaller, more protease resistant states . In addition, botulinum neurotoxin A inhibits exocytosis by perturbing the syntaxin:SNAP-25 ratio in binary intermediates. Dermatol Surg, 2002 Feb, 28(2), 168 - 71 Botulinum toxin A: successful décolleté rejuvenation; Becker-Wegerich PM et al.; BACKGROUND: Decollete wrinkles develop with age . In women more than 35 years of age these wrinkles are still transient, but become permanent at about age 50 . In a substantial number of women decollete wrinkles, seem to be associated with an insertion of platysma exceeding the second intercostal space . We report botulinum A toxin therapy of these wrinkles in five patients . OBJECTIVE: To show the effect of botulinum A toxin on decollete wrinkles . METHODS: All five women with decollete lines treated with botulinum A had different varieties of the platysma muscle inserting deep down beneath the fourth intercostal space . During platysma contraction injection points were marked and a certain dosage of toxin was applied . RESULTS: Two weeks after therapy a significant improvement of the treated decollete region was observed . CONCLUSION: These observations indicated that botulinum A toxin can be an effective and safe method in the temporary management of decollete wrinkles . It should therefore be considered as a new adjuvant treatment in cosmetic decollete rejuvenation. Dermatol Surg, 2002 Feb, 28(2), 149 - 52 Decreased tear expression with an abnormal Schirmer's test following botulinum toxin type A for the treatment of lateral canthal rhytides; Matarasso SL; BACKGROUND: Inactivation of muscles of facial expression by chemodenervation with botulinum toxin remains an off-label indication . Nevertheless, it continues to be a safe and effective technique to improve dynamic rhytides and is the treatment of choice for the hypertrophic lateral fibers of the orbicularis oculi muscle that can cause the superimposed crow's feet . OBJECTIVE: Although infrequent and self-limiting, the complication of unexpected muscle weakness from toxin diffusion or erroneous placement is documented . METHODS: However, injection into the pretarsal portion of the orbicularis oculi muscle resulting in unilateral ocular irritation and diminished tear expression as evidenced by a dry eye and an abnormal Schirmer's test has rarely been reported . Direct injection into the pretarsal fibers of the muscle as opposed to diffusion of the toxin into the muscle fibers or the lacrimal gland was consistent with the onset of action of the toxin and the prolonged duration of the ocular symptoms . RESULTS: Treatment consisted of ocular lubrication until the effects of the toxin dissipated and muscle tone returned . Subsequent treatment did not result in a result in a recurrence of adverse sequelae . CONCLUSIONS: Facial muscles are small, not isolated, and often have fibers that interdigitate . An important factor in the administration of botulinum toxin is the identification of the muscles responsible for the corresponding rhytide . Precise knowledge of muscular anatomy and function will aid in minimizing this and other potential complications. J Mol Neurosci, 2001 Dec, 17(3), 303 - 10 Tetanus toxin modulates serotonin transport in rat-brain neuronal cultures; Pelliccioni P et al.; As has been previously described, tetanus toxin (TeTx) and its H(C) fragment inhibit the sodium-dependent 5-hydroxytryptamine (5-HT) uptake in rat-brain synaptosomes, probably through a kinase mechanism affecting the 5-HT transporter . Now, the inhibition of 5-HT uptake in neurons in primary culture by TeTx in a dose-dependent manner is described in this work . This effect is also produced by the nontoxic C-terminal fragment of the TeTx heavy chain (H(C)-fragment), indicating that 5-HT uptake inhibition is a consequence of the toxin binding to the plasmatic membrane and not to its catalytic activity . This conclusion is supported by the fact that the 5-HT accumulation was not inhibited by the light chain of TeTx or the toxoid, and was even potentiated by botulinum neurotoxin A . These results correlate with the activation of phosphoinositide-phospholipase C activity in the cultures used in this study, this activity only being enhanced by TeTx and by its Hc-fragment . On the other hand, the use of tyrosine phosphorylation modulators indicates that both Na3VO4 and basic fibroblast growth factor (bFGF) produce an enhancement of 5-HT uptake in this system, which is also sensitive to TeTx inhibition . On the other hand, genistein alone is able to reduce the 5-HT transport in cultured neurons, and this effect did not appear to be additive to that elicited by TeTx . This result suggests that TeTx and genistein may share some events in their respective mechanisms of action . Furthermore, the incubation at different concentrations of 12-O-tetradecanoylphorbol 13-acetate (TPA) confirms the involvement of protein kinase C (PKC) in 5-HT transport modulation in rat-brain neuronal primary cultures . In summary, we shall demonstrate in this work that TeTx induces, through its Hc fragment, an inhibition of both basal and stimulated serotonin uptakes in primary neuronal cultures, in parallel to the activation of phosphoinositide-phospholipase C activity and PKC activation. Vaccine, 2002 Feb 22, 20(11-12), 1640 - 8 Genetic and immunological comparison of anti-botulinum type A antibodies from immune and non-immune human phage libraries; Amersdorfer P et al.; Understanding the antibody response in botulinum intoxication is important for vaccine design and passive prophylaxis . To investigate this activity, we have studied the immune response to BoNT/A (botulinum neurotoxin serotype A) binding domain (HC) at the molecular level using phage display . The scFv antibodies were isolated from V-gene repertoires prepared from (a) human volunteer immunized with pentavalent botulinum toxoid and (b) non-immune human peripheral blood lymphocytes and spleenocytes . A large panel of serotype specific phage expressing botulinum binding scFv could be selected from both libraries . Epitope mapping of immune scFv binders towards BoNT/A HC revealed surprisingly a limited number of scFv recognizing conformational epitopes that corresponded to two distinct groups, clusters I and II . Only scFv from cluster I exhibited neutralizing activity in the mouse hemidiaphragm assay . Anti- BoNT/A HC clones derived from a non-immune library could be conveniently grouped into clusters III-XI and appeared to share no overlapping epitopes with cluster I or II . In addition they showed no neutralization of toxin at biologically significant concentrations . We therefore suggest that a vaccine based on the pentavalent botulinum toxoid directs the humoral immune response to a limited number of immunodominant epitopes exposed on the binding domain HC. J Pediatr Orthop, 2002 Mar-Apr, 22(2), 169 - 72 Outcome of medial versus combined medial and lateral hamstring lengthening surgery in cerebral palsy; Kay RM et al.; Pre- and postoperative gait analysis and static measurements from 37 children with cerebral palsy who underwent hamstring lengthening were evaluated . Significant improvements in static and kinematic measures were noted after surgery in both groups . Although the differences were not statistically significant, there was a suggestion that combined medial/lateral hamstring lengthening may provide greater improvement in popliteal angle and maximum knee extension in stance . However, there also appears to be a greater risk of knee hyperextension during gait after combined medial and lateral hamstring lengthening than after medial hamstring lengthening alone . Postoperative calf spasticity also appears to be a risk factor for postoperative knee hyperextension . Assessment of calf spasticity may be important in patients undergoing medial and lateral hamstring lengthening . Additional treatments such as bracing and/or botulinum toxin injections to the calf to control equinus and knee hyperextension may be beneficial. J Pediatr Orthop, 2002 Mar-Apr, 22(2), 165 - 8 Technique for iliopsoas ultrasound-guided active electromyography-directed botulinum a toxin injection in cerebral palsy; Willenborg MJ et al.; Symptomatic hip flexion deformity secondary to iliopsoas spasticity may interfere with gait, impair sitting balance, or contribute to hip subluxation or dislocation . A nonsurgical, minimally invasive technique to ameliorate iliopsoas spasticity is presented . The technique uses intramuscular injections of botulinum A toxin to provide selective neuromuscular blockade of the iliacus or psoas muscles or both . Because of the anatomic location of the target muscles, this technique uses ultrasound guidance for needle placement . Active electromyographic stimulation is used to verify the needle position adjacent to active myoneural interfaces . The authors' experience to date includes the treatment of 28 patients (53 hips) . Use of this technique has resulted in improved hip range of motion . No intraoperative or postoperative adverse events or complications have been observed. Surgery, 2002 Feb, 131(2), 179 - 84 Effectiveness of higher doses of botulinum toxin to induce healing in patients with chronic anal fissures; Brisinda G et al.; BACKGROUND: Botulinum toxin induces healing in patients with idiopathic anal fissures . METHODS: One hundred-fifty patients with posterior anal fissures were treated with botulinum toxin injected in the internal anal sphincter on each side of the anterior midline . Subjects were randomized into 2 treatment groups based on the number of units of botulinum toxin injected . Patients in group I were treated with 20 units of botulinum toxin and, if the fissure persisted, were retreated with 30 units . Patients in group II were treated with 30 units and retreated with 50 units, if the fissure persisted . RESULTS: The 2 groups were comparable in age, gender distribution, duration of symptoms, resting pressure, and maximum voluntary pressure at anorectal manometry . One month after the injection, examinations revealed complete healing in 55 patients (73%) from group I and 65 patients (87%) from group II (P =.04) . Five patients from group II reported a mild incontinence of flatus that lasted 2 weeks after the treatment and disappeared spontaneously . The values of the resting anal pressure (P=.3) and the maximum voluntary pressure (P =.2) did not differ between the 2 groups . At 2 months' evaluation, a healing scar was found in 67 patients (89%) from group I and 72 patients (96%) from group II . A relapse of the fissure was observed in 6 patients (8%) from group I who had a healing scar at 1 month, and 2 other patients never healed . A persistent fissure was present in 3 patients from group II who had no other symptoms . CONCLUSIONS: Botulinum toxin injected into the internal anal sphincter is effective in managing anal fissures and avoiding permanent complications . All patients were treated with the active drug and healed after 1 or 2 successive treatments . The results also confirm that higher doses account for a higher success rate, with little increase in complications or side effects, which is probably related to the diffusion of the toxin to the external sphincter. Funct Neurol, 2001 Oct-Dec, 16(4), 317 - 23 Short-term effects of "botulinum toxin a" as treatment for children with cerebral palsy: kinematic and kinetic aspects at the ankle joint; Galli M et al.; Botulinum toxin A (BTA) therapy plays several roles in the management of paediatric cerebral palsy (CP) . However, few studies contain objective documentation of gait changes . The main aim of this study was to provide objective information on the outcome of the treatment . Gait analysis data from 20 normal subjects and 23 CP children were collected before and after BTA injections into the gastrocnemius-soleus complex . The follow up was performed 1 month after the first injection . The kinematic and kinetic data revealed significant improvements in dynamic ankle dorsiflexion, both in stance and in the swing phase, an improvement of equinus foot upon initial contact and better support in stance . The results of this study are promising, but studies of other joints involved in gait, such as the knee, are also needed. Eur J Neurol, 2001 Nov, 8 Suppl 5, 194 - 202 Botulinum toxin type A in the management of equinus in children with cerebral palsy: an evidence-based economic evaluation; Houltram J et al.; INTRODUCTION: The aim of this study was to compare two methods of conservative management of calf spasticity and equinus gait--intramuscular injection of botulinum toxin type A (BTX-A) and serial casting . An economic evaluation framework was adopted to assess whether BTX-A offers value for money in the management of equinus gait due to calf spasticity in children with cerebral palsy . Short- to medium-term health care costs and outcomes were estimated for the comparison . This study was embarked upon to provide clinical and economic data as part of an application to the Pharmaceutical Benefits Advisory Committee (PBAC) for the reimbursement of BOTOX by the Australian Commonwealth Government . This is the primary mechanism for reimbursement of pharmaceuticals in Australia, as they are not routinely reimbursed through health insurance companies . The perspective of the analysis was that of the Australian health system . METHODOLOGY: Randomized controlled trials (RCTs) exist comparing one treatment cycle of BTX-A with serial casting (Corry et al., 1998; Flett et al., 1999) . A long-term prospective study provided data on multiple cycles of BTX-A treatment in a more naturalistic setting (Boyd et al., 1999) . A simple economic modelling approach was used to establish resource utilization by treatment arm . Only direct medical costs were considered (BTX-A, medical personnel time and medical consumables) . MAIN MEASURES: Clinical efficacy was obtained from the randomized controlled trials (Corry et al., 1998; Flett et al., 1999) . Patient/parent preference was obtained from long-term follow-up (Corry et al., 1998) and a preference questionnaire (Flett et al., 1999) . Australian treatment patterns and patient demographics were obtained from the naturalistic study (Boyd et al., 1999) . RESULTS: The RCTs demonstrated equivalent efficacy of BTX-A and serial casting; however, with BTX-A the effect lasted longer and was clearly the preferred treatment . For patients with hemiplegia the costs of an episode of treatment with BTX-A or serial casting are ($AUD) $595 and $435, respectively, and thus the additional costs associated with BTX-A are $160 . The corresponding costs for patients with diplegia are $1045 for BTX-A treatment and $870 for serial casting and thus the additional cost associated with BTX-A is $175 . With an overall treatment duration of 3.7 years and an average treatment interval of 10 months, patients would receive an average of 5.4 treatments . Thus, for patients with hemiplegia the total additional cost, discounted at 5% annually, for BTX-A is $793 . For patients with diplegia the total additional cost for BTX-A is $867 . CONCLUSIONS AND CLINICAL INTERPRETATIONS: BTX-A is an effective, safe and acceptable treatment modality and is associated with only a modest increase in direct medical costs per child per year . BTX-A can be considered a valuable and cost-effective treatment in the conservative management of equinus due to calf spasticity in children with cerebral palsy . This conclusion is supported by the acceptance of the Pharmaceutical Benefits Advisory Committee (PBAC) recommendation that BOTOX should attract a full Government subsidy in Australia. Eur J Neurol, 2001 Nov, 8 Suppl 5, 167 - 77 Outcome measurement of effectiveness of botulinum toxin type A in children with cerebral palsy: an ICIDH-2 approach; Boyd RN et al.; The ICIDH-2 serves as a useful framework for differentiating measurement by dimensions of the disabling process . Such differentiation is important to achieve more valid measurement of health related outcomes . We have attempted to examine one intervention, treatment with botulinum toxin type A, for one patient population, children with cerebral palsy, and to describe the outcome measures used in the evaluation of that intervention using this evolving classification system . This process supports the concept that measurement of health outcomes should focus on the nature and extent of functional limitations in physical, social and psychological domains . The selection of measurement outcomes must be determined not only by the requirements of the scientific process but also by the needs of the patients who are the intended beneficiaries of the intervention. Eur J Neurol, 2001 Nov, 8 Suppl 5, 150 - 66 Management of upper limb dysfunction in children with cerebral palsy: a systematic review; Boyd RN et al.; Effective use of the upper limb can impact on educational outcomes, participation in activities of daily living and vocational options for many children with cerebral palsy (CP) . This article presents the results of a systematic review of the literature on the management of upper limb dysfunction in children with CP . The range of management options includes therapies such as physiotherapy, occupational therapy, neurodevelopmental therapy and conductive education; peripheral splinting and casting; focal or generalized pharmacotherapy; and surgery to improve upper limb function or correct deformity . A literature search identified 60 papers, of which four were randomized controlled trials and 44 were prospective studies with objective outcome measures . Principal studies undertaken for each type of treatment and the efficacy of the different types of treatment were critically evaluated . In addition, the current level of evidence for each study was evaluated according to Sackett's (1989) model and ICIDH-2 classification . A close examination of two relatively new treatments for upper limb spasticity, constraint induced movement therapy and botulinum toxin type A (BTX-A) was conducted with reference to more extensive data on the efficacy of BTX-A in the lower limb. Eur J Neurol, 2001 Nov, 8 Suppl 5, 145 - 9 Botulinum toxin type A injections in the spastic upper extremity of children with hemiplegia: child characteristics that predict a positive outcome; Fehlings D et al.; Evidence is increasing to suggest that botulinum toxin type A (BTX-A) plays a role in the management of upper extremity spasticity in the paediatric population . However, little information is available on the clinical characteristics of the child that predict a response to this intervention . Our research group previously published a randomized controlled trial demonstrating that BTX-A injection improves function of the upper extremity of children with spastic hemiplegia . In the present paper, we evaluate the child characteristics that predict a positive response to the BTX-A injections in the randomized treatment group . The treatment group was divided into positive functional responders and nonresponders using a cut score of a change of 10 points on the Quality of Upper Extremity Skills Test (QUEST) . A two-way analysis of variance procedure was done comparing the following baseline characteristics: function as scored on the QUEST and the Pediatric Evaluation of Disability Inventory (PEDI) self-care domain, grip strength, upper extremity spasticity and age . Grip strength was significantly higher in responders with a P-value of 0.001 . Young age approached significance with a P-value of 0.05 . Correlation of change scores on the QUEST with baseline characteristics in the treatment group yielded similar results . BTX-A causes a reduction in spasticity and strength; we postulate that if the hand is weak initially, BTX-A can decrease hand function . Two case reports are presented that highlight the importance of grip strength and age. Eur J Neurol, 2001 Nov, 8 Suppl 5, 136 - 44 Management of the upper limb with botulinum toxin type A in children with spastic type cerebral palsy and acquired brain injury: clinical implications; Autti-Ramo I et al.; The aim of this article is to describe our clinical experience in treating muscle imbalance in 49 children with spastic upper extremity involvement . We discuss four cohorts of children treated with botulinum toxin type A (BTX-A), each with different treatment objectives . In the first group, 27 children were treated for functional improvement and, of these, 23 had a positive effect, while four had no objective benefit . In the second group, eight children were treated for purposes of presurgical planning; of these, four were referred for surgery, three continued with serial treatment and one child did not benefit from injection . The third group comprised six children who were treated to improve posture and care: in this group, four children demonstrated clear benefit and two children lost some function subsequent to injection . Finally, a fourth group of seven children were treated after acquired brain injury (three with severe tetraplegia, four with hemiplegia) . In this group, all children experienced spasticity relaxation and two children with hemiplegia also gained functional benefit . In terms of adverse events, deterioration of upper extremity function was poorly tolerated but limited to the first 1--3 weeks postinjection . Grip strength or thumb grip were diminished if too high doses were used . Overall, our results with BTX-A were rewarding in children with no fixed contracture, good motor learning capacity and high motivation to train . Additionally, BTX-A treatment has proven valuable for counteracting spasticity in children with acquired brain injury . This treatment modality may not, however, be an appropriate treatment option for all children with severe upper extremity spasticity, due to the shorter duration of effect and the potential reduction in functional abilities seen in this cohort . In all cases, the selection of muscles to be treated needs careful clinical assessment . Dynamic EMG analysis should be performed whenever required to aid muscle selection, especially in children with spasticity combined with dystonia . Evaluation of M-responses suggests that for the forearm muscles, doses of BTX-A above 1.5 U/kg/muscle should not be used. Eur J Neurol, 2001 Nov, 8 Suppl 5, 127 - 35 Spasticity management in the child with spastic quadriplegia; Gormley ME Jr et al.; In children with spastic quadriplegia, also described as 'whole body involvement', spasticity can interfere with motor function, contributes to the development of deformities and adversely impacts on care, positioning, and comfort . In this population, spasticity interventions address goals such as improving comfort, reducing pain, easing the burden of carers, slowing the progression of musculoskeletal deformities and perhaps improving function . Children with severe diplegia are distinguished from those with quadriplegia by their ability to ambulate, as well as by a greater emphasis being placed on functional motor goals even though similar treatment modalities are often employed to manage spasticity . The many treatment options currently available include, but are not limited to, botulinum toxin type A, phenol neurolysis, oral medications, intrathecal baclofen, selective dorsal rhizotomy, and orthopaedic surgery . The integration of these treatment modalities can help to optimize the overall care and function for a child with spastic quadriplegia or severe diplegia . However, the development of a management programme is complex and needs to take into account many factors, including age, weight and nutritional status, rate of progression of musculoskeletal deformities, developmental potential, comorbid conditions, current functional status and prognosis, and family and patient treatment goals . Children with marked spasticity are likely to benefit from a combination of interventions, rather than a single treatment modality . Because of these complexities, management should be planned and coordinated by a multidisciplinary team of medical and allied health professionals which recognizes the central role of the family in all decisions . Once the special characteristics of the child with spastic quadriplegia and the various treatment options are understood, outcomes can be maximized. Eur J Neurol, 2001 Nov, 8 Suppl 5, 120 - 6 Medium-term functional benefits in children with cerebral palsy treated with botulinum toxin type A: 1-year follow-up using gross motor function measure; Linder M et al.; One of the main goals when treating spasticity is to relieve pain and improve function . Intramuscular injection of botulinum toxin type A (BTX-A) has gained widespread acceptance in the treatment of spastic cerebral palsy . Several studies have clearly shown the short-term functional benefit of BTX-A treatment . Information is limited, however, on the efficacy of medium and long-term regimens, using repeated injection of BTX-A . The aim of the present open-label, prospective study was to evaluate functional outcome in children with spastic cerebral palsy after 1 year of treatment with BTX-A, using the Gross Motor Function Measure (GMFM) as a validated outcome measure . Patients (n=25, age 1.5--15.5 years) were treated with BTX-A for adductor spasm (n=12) or pes equinus (n=13) . The local effect was evaluated using passive range of motion and modified Ashworth Scale . Apart from a significant improvement in joint mobility and reduction of spasticity compared to pretreatment values (P < 0.01), we demonstrated a significant improvement of gross motor function after 12 months of treatment, with a median gain of 6% in total and goal scores (P < 0.001) . An increase in GMFM scores was particularly evident in younger and moderately impaired children (Gross Motor Function Classification System level III) . Whether the observed improvement in gross motor function in children with cerebral palsy is specifically related to therapy with BTX-A or represents at least in part the natural course of motor development still needs clarification. Eur J Neurol, 2001 Nov, 8 Suppl 5, 109 - 19 The effect of botulinum toxin type A and a variable hip abduction orthosis on gross motor function: a randomized controlled trial; Boyd RN et al.; Hip displacement is the second most common deformity after equinus in children with cerebral palsy (CP), and may result in dislocation, pain, fixed deformity and loss of function . We studied the combined effects of intramuscular injections of botulinum toxin type A (BTX-A) to the adductors and hamstrings and a variable hip abduction orthosis (SWASH), on gross motor function, hip displacement and progression to surgery, in a randomized clinical trial . Thirty-nine children, with bilateral spastic cerebral palsy, and mean age 3 years + 2 months (range 1 year+7 months--4 years +10 months) entered the trial . Gross Motor Function Classification System (GMFCS) levels were as follows: one child was level II, 11 were level III, 13 were level IV and 14 were level V . After concealed randomization, 20 were allocated to the control group and 19 to the intervention group . Thirty-five children completed the follow up at 1 year . The novel intervention group received up to 4.0 U BOTOX/kg/muscle, 16 U/kg/body weight every 6 months plus the use of a SWASH brace . The control group received clinical best practice comprising physiotherapy but no hip abduction bracing . Both groups showed improvements in total Gross Motor Function Measure (GMFM) score {mean 6.0% BTX-A group; 6.1% Control; 95% CI -- 6.7, 6.5 (NS)}, however, there was no additional treatment effect for the study group . There were similar improvements on GMFM goal scores and GMFM-66 scores, but again no additional treatment effect was observed . Multiple regression of change in total GMFM by GMFCS classification for each group showed greater improvement in the total scores from baseline in the BTX-A/SWASH treated group than the control group . In the first year, nine children (two in the intervention group and seven in the control group) required soft tissue surgery because of progressive hip migration in excess of 40% . A longer-term follow up of a larger cohort may be required to determine the effect of the combined treatment on hip displacement. Eur J Neurol, 2001 Nov, 8 Suppl 5, 88 - 97 Single event multilevel botulinum toxin type A treatment and surgery: similarities and differences; Molenaers G et al.; The present study attempts to provide objective evidence of two treatment options for children with cerebral palsy (CP): multilevel botulinum toxin type A (BTX-A) injections and multilevel surgery . The purpose of the study was to clarify the differences and the similarities, and common treatment principles of both treatment strategies . Objective three dimensional gait analysis data were studied retrospectively in two patient groups pre- and post-treatment (randomly selected from a group of children that were treated between 1998 and 1999) . In the first group, 29 children with CP were managed with BTX-A injections according to an integrated multilevel approach (Molenaers et al., 1999a) . A second group of 23 children with CP were managed by a more traditional single event multilevel surgery, also according to an integrated approach . Our aim was to evaluate the differences as well as the similarities between both patient groups, using a set of 56 parameters selected from three-dimensional gait analysis . The unifying concept between management with BTX-A injections and orthopaedic surgery was the adoption of a multilevel approach at one session . The groups demonstrated considerable differences with respect to age, pretreatment condition and amount and level of improvement after treatment . The children who received BTX-A were typically younger, and showed primary gait problems in the distal joints, whereas the children who underwent surgery demonstrated a higher frequency of gait deviations in the transverse plane and had more complications . Although the benefit of both treatments was confirmed by the present study, a difference in the amount and level of improvement was also demonstrated . In conclusion, these treatment modalities should be regarded as complementary rather than mutually exclusive treatments, with both calling for an integrated approach. Eur J Neurol, 2001 Nov, 8 Suppl 5, 75 - 87 A randomized study of combined botulinum toxin type A and casting in the ambulant child with cerebral palsy using objective outcome measures; Desloovere K et al.; It is recognized that objective gait analysis is of great value in planning a multilevel botulinum toxin type A (BTX-A) treatment . After BTX-A treatment, objective outcome measures can provide new and interesting information for each individual child with cerebral palsy (CP) . Moreover, by studying group results, we may evaluate our treatment hypotheses . The present prospective study attempts to document the effect of integrated multilevel BTX-A treatment on objective gait parameters and to define the optimal strategy for the combined treatment of BTX-A with casting in children with cerebral palsy . Objective three-dimensional gait analysis (3DGA) data were collected pre- and 2 months post-treatment, in two randomized patient groups: a first group of 17 children treated with lower leg casting prior to BTX-A injections, and a second group of 17 patients who received casting immediately after injections . The present study demonstrates that improved gait can be achieved after a multilevel BTX-A treatment, combined with casting, using a set of 90 gait parameters . The most pronounced improvement was seen at the ankle joint . The results in the knee, hip and pelvis imply that multilevel treatment of the child with CP should start at an early age, in order to prevent development of muscle contractures . Slightly more pronounced benefits, mainly in the proximal joints, were seen for the children who were casted after injections as compared to the children who were casted before injections. Eur J Neurol, 2001 Nov, 8 Suppl 5, 59 - 74 Treatment of functional limitations at the knee in ambulatory children with cerebral palsy; Chambers HG; The gait of ambulatory children with cerebral palsy frequently involves abnormal knee motion . Spasticity, muscle contracture formation, impairments of motor control, weakness, balance deficits, and extrapyramidal motions can all contribute to the functional limitations imposed at the knee . Careful clinical evaluation of the child and their gait must be performed in order to determine the best individual course of treatment . Often, three-dimensional motion analysis with assessment of muscle activity and force is necessary to completely assess the complexities of gait . Several typical gait patterns have been described involving the knee, including 'jump knee', 'crouch', 'true equinus', 'apparent equinus', 'recurvatum' and 'stiff knee' gait . Each of these gait patterns is defined here and discussed using case examples . These typical gait patterns are usually accompanied by involvement at the hip and ankle and may be combined with transverse plane rotational abnormalities . Treatment options such as rehabilitation (physiotherapy, casting, strengthening, and/or orthoses), spasticity management (intramuscular injections of phenol, alcohol, and botulinum toxin type A) and orthopaedic approaches are discussed for each entity. Eur J Neurol, 2001 Nov, 8 Suppl 5, 50 - 8 The effect of botulinum toxin type A on the functional ability of the child with spastic hemiplegia a randomized controlled trial; Love SC et al.; It has been demonstrated that botulinum toxin type A (BTX-A) injections reduce spasticity and improve muscle growth in children with spasticity . It has been postulated that BTX-A allows the learning of more normal movement patterns . The aim of this study was to measure the effect of this treatment on functional ability, as measured by the Gross Motor Function Measure (GMFM), in children with spastic hemiplegic cerebral palsy . Children of 3--13 years and meeting the selection criteria were randomly allocated to the control or injection group using a matched pair design . A match constituted a child within 6 months of age with the same Modified Ashworth Score (MAS) for the gastroc-soleus and within 10% of the same goal scores on the Gross Motor Function Measure . Twelve matched pairs were enrolled . Outcomes were measured on enrolment and at 1, 3 and 6 months post injection . The time course of the response to BTX-A was assessed with measurements of the MAS, dynamic range of motion (R1) and static muscle length (R2) . Motor function was assessed using the 88-item GMFM and parental satisfaction with a 10-point visual analogue scale . Within pair comparisons of the GMFM using the Wilcoxon signed rank test indicated that the treatment group made significantly greater gains than controls at 3 months (P=0.02) with even greater differences seen at 6 months (P=0.004) . Using parametric statistics, the intrapair difference in proportional change of GMFM increased from 35% (4 to 65) at 3 months to 52% (17--87) at 6 months . Response to injection was confirmed by a decrease in MAS in the treatment group and very little change in controls . This difference was significant (P=0.002) at 3 months and was attenuated but still significant (P=0.016) at 6 months; the difference in proportional change decreased from 44% at 3 months to 22% at 6 months . Changes in R1 reflected those of MAS in the treatment group and deteriorated significantly over the study period in controls . Parents of children in the treatment group were more satisfied than controls, but satisfaction scores did not correlate with changes in function or technical outcomes suggesting that this may be a placebo effect . The changes in GMFM correlated with changes in technical outcomes at 3 months, suggesting a causal relationship . The intrapair differences in GMFM continued to increase even after the local response to injection had started to wane. Eur J Neurol, 2001 Nov, 8 Suppl 5, 30 - 9 Botulinum toxin type A management of spasticity in the context of orthopaedic surgery for children with spastic cerebral palsy; Graham HK; Cerebral palsy is the most common cause of physical disability affecting children in developed countries . Although cerebral palsy is, by definition, a 'static encephalopathy' the associated musculoskeletal pathology is progressive and current definitions are therefore somewhat inadequate . Understanding the stages of the musculoskeletal pathology is fundamental to understanding current management strategies, including spasticity management, strengthening programmes and deformity correction by orthopaedic surgery . In this review, a number of new management strategies are described, in which spasticity management by intramuscular injections of botulinum toxin type A and deformity correction, by orthopaedic surgery, are combined. Eur J Neurol, 2001 Nov, 8 Suppl 5, 21 - 9 Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions; Aoki KR et al.; Botulinum toxin type A is an important therapeutic agent for the treatment of movement and other disorders . As the clinical uses of botulinum toxin type A expand, it is increasingly important to understand the biochemical and pharmacological actions of this toxin, as well as those of other botulinum toxin serotypes (B-G) . Botulinum neurotoxin serotypes exhibit differences in neurotoxin complex protein size, percentage of neurotoxin in the activated or nicked form, intracellular protein target, and potency . These properties differ even between preparations that contain the same botulinum toxin serotype due to variations in product formulations . As demonstrated in preclinical and clinical studies, these differences result in a unique combination of efficacy, duration of action, safety, and antigenic potential for each botulinum neurotoxin preparation. Eur J Neurol, 2001 Nov, 8 Suppl 5, 1 - 20 Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systematic review; Boyd RN et al.; Management of children with cerebral palsy (CP) is the focus of considerable resources in many countries, so that evaluation of the efficacy for new and established treatments is imperative . Botulinum toxin type A (BTX-A) is a relatively new method of spasticity management in children with cerebral palsy . It has been the focus of extensive research since its application to cerebral palsy 10 years ago . In a systematic review relating to the management of the lower limb in cerebral palsy 156 papers were identified . These were categorized according to Sackett and the World Health Organisation International Classification of Impairments, Disabilities and Handicaps model . We identified 10 randomized trials evaluating the use of BTX-A in the lower limb in children with cerebral palsy in a systematic review . A meta-analysis showed the pooled risk difference between BTX-A and placebo in three trials was 0.25 (95% CI 0.13, 0.37) and 0.23 (95% CI -0.06, 0.53) for two trials of BTX-A and casting using the physicians rating scale . These represent moderate treatment effects that are dosage-dependent . Outcomes were also compared for function in five studies . The type of evidence for BTX-A was graded by each treatment indication and directions for future research were then drawn from the available evidence. Br J Surg, 2002 Jan, 89(1), 116 - 9 Botulinum toxin A in the treatment of patients with Frey syndrome; Beerens AJ et al.; BACKGROUND: This was a prospective study of the treatment of Frey syndrome, also known as gustatory sweating, with botulinum toxin A . METHODS: Thirteen patients with a mean involved skin area of 53 (range 36-80) cm2, as assessed with the Minor starch-iodine test, were treated with 0.1 ml toxin (75 units/ml) injected intracutaneously into every 4 cm2 of involved skin . The mean total dose was 100 (range 67.5-150) units . Treatment results were assessed every 3 months with the Minor test . The Frey Questionnaire Card (FQC) was used for subjective assessment . The mean follow-up after primary treatment was 20 (range 9-24) months . Treatment was repeated if the symptoms recurred . RESULTS: After 3 months 11 of the 13 patients showed a decrease of gustatory sweating of more than 90 per cent . All but one patient with a follow-up of 2 years suffered recurrent gustatory sweating . The mean recurrence-free period after primary treatment was 11 months and that after secondary treatment was 15 months . FQC score and objective assessment correlated well . Treatments were well tolerated, although two patients developed a temporary perioral muscle paresis . CONCLUSION: Botulinum toxin A produces good results in the treatment of Frey syndrome . Repeated treatment improves on the results of primary treatment. Ugeskr Laeger, 2002 Feb 4, 164(6), 762 - 5 {Treatment of Frey syndrome with intracutaneous injections of botulinum toxin}; Madsen JB et al.; In a prospective study, we have examined the efficacy of intracutaneous injections of botulinum toxin in Frey's syndrome . In a controlled study, the long term results after surgical treatment for parotid tumors were investigated in 98 consecutive patients . Patients, who reacted positive by Minor's iodine-starch test, and who had subjective complaints too, were offered treatment . A total of four patients entered the study . The affected area was visualised by Minor's iodine-starch test . The coloured areas were injected with botulinum toxin (Botox) 2.5 U/0.1 ml . We injected 0.5 U/cm2 . The distance between each injections points was 1 cm . All patients became free of symptoms . The injections were given with little discomfort to the patients and no side effects . At the control one year after the injections three patients had minor recurrent complaints, which were treated successfully by reinjections . Botulinum toxin injections are thus safe and effective in the treatment of FS. J Neurosci, 2002 Feb 15, 22(4), 1266 - 72 The core membrane fusion complex governs the probability of synaptic vesicle fusion but not transmitter release kinetics; Finley MF et al.; Synaptic vesicle fusion is driven by the formation of a four-helical bundle composed of soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptors (SNAREs) . Exactly how the structural interactions that lead to the formation of this complex relate to neurotransmitter release is not well understood . To address this question, we used a strategy to "rescue" synaptic transmission after proteolytic cleavage of the synaptosome-associated protein of 25 kDa (SNAP-25) by botulinum neurotoxin E (BoNtE) . Transfection of CA3 hippocampal pyramidal cells with BoNtE-resistant SNAP-25 restored synaptic transmission . Additional mutations that alter the interaction between SNAP-25 C-terminal coil and the other SNARE coils dramatically reduce transmitter release probability but leave the kinetics of synaptic responses unaltered . These data indicate that at synapses, SNARE interactions are necessary for fusion but are not the rate-limiting step of neurotransmission. Eur Neurol, 2002, 47(2), 118 - 21 Antibody-induced botulinum toxin therapy failure: can it be overcome by increased botulinum toxin doses? Dressler D, Munchau A, Bhatia KP, Quinn NP, Bigalke H. In some patients treated with botulinum toxin type A (BT) therapy failure occurs due to the formation of antibodies against BT (BT-AB) . We investigated whether increased BT doses can overcome this form of therapy failure . Eight patients with cervical dystonia, secondary BT therapy failure and evidence of BT-AB formation in the mouse diaphragm bioassay received BT test doses (Dysport, Ipsen Ltd., Maidenhead, Berks, UK) into one of their sternocleidomastoid muscles . Test doses were increased in three steps at 3-month intervals and their effect on the amplitude of the electromyographic activity of the sternocleidomastoid muscle under maximal isometric activation (M-EMG) was measured and compared to a control group . In step 1 (200 or 300 MU) the M-EMG reduction was 12 +/- 13% compared to 85 +/- 10% (200 MU) and 83 +/- 9% (300 MU) in the control group . In step 2 (400, 600 or 800 MU) the M-EMG reduction was 25 +/- 21% compared to 78 +/- 7% (400 MU) in the control group . In step 3 (1,600 or 1,800 MU) the M-EMG reduction was 24 plus minus 10% . Side effects were not observed in any of the patients studied . In 1 patient with partial secondary BT therapy failure, with a low BT-AB titre (0.0015 U/ml) and with a moderately pathological M-EMG reduction of 40% with 200 MU a normal M-EMG reduction of 71% could be regained with 800 MU . In three subsequent therapeutic injection series with quadrupled BT doses in all target muscles the original therapy outcome could be regained and maintained . Side effects or increasing BT-AB titres were not observed . Even massively increased BT doses cannot overcome BT-AB-induced complete secondary therapy failure . However, in patients with partial secondary therapy failure, low BT-AB titres and a moderately pathological M-EMG reduction, increased BT doses might regain and maintain normal BT efficacy without induction of side effects or increasing BT-AB titres . J Eur Acad Dermatol Venereol, 2001 Nov, 15(6), 555 - 8 Botulinum toxin A for palmar hyperhidrosis; Wollina U et al.; OBJECTIVE: We evaluated the efficacy and safety of intracutaneous injections of botulinum toxin A on severe palmar hyperhidrosis . METHODS: Ten patients with recalcitrant palmar hyperhidrosis were treated with intercutaneous injections of botulinum toxin A (Botox; 200 U for each hand) . Patients were followed up to 23 months (mean +/- SD: 12.1 +/- 6.2 months) . RESULTS Botulinum toxin significantly reduced abnormal sweating within 1 week in 100% of the patients . In six patients with a follow-up of 12 months or more the antisudorific effect lasted 12.3 +/- 5.5 months . The longest response duration was 22 months . Repeated treatment was performed in five patients with unchanged clinical efficacy . The only side-effect was tolerable pain from the intracutaneous injections in patients where a nerve block was not performed . CONCLUSIONS: Botulinum toxin A (200 U Botox per palm) was able to induce long-term remission in palmar hyperhidrosis without significant acute and long-term side-effects . Strictly intracutaneous injection of small volumes is recommended . So far, response to repeated treatments did not show evidence of neutralizing antibody induction. Strabismus, 2001 Dec, 9(4), 217 - 20 Squint surgery in the over sixties; Dawson E et al.; We examined the indications for strabismus surgery in patients 60 years of age or older . A retrospective review was carried out of 111 case records of such patients operated on between January 1992 and May 1999 . There were 59 females and 52 males, ranging in from 60 to 90 years (mean 67.3 years) . The diagnoses were varied: the largest groups were cranial nerve palsies and consecutive strabismus . Fifty-six patients demonstrated binocular potential pre-operatively and 60 post-operatively . Twenty-three patients underwent reoperation . Twenty-eight patients also received botulinum toxin . The mean follow-up was 15 months, 54 patients were discharged within 6 months . Elective strabismus surgery in this age group constituted 7% of strabismus surgery activity (single surgeon) . There were no complications . There is a demand for strabismus surgery in this ever increasing age group. Mov Disord, 2002 Jan, 17(1), 198 - 200 Riluzole therapy in cervical dystonia; Muller J et al.; We conducted a 6-week open-label pilot study with blinded video rating of riluzole (50 mg twice a day) in six patients with cervical dystonia (CD) refractory to botulinum toxin A and oral pharmacological treatment . The Tsui rating scale served as primary efficacy measure and improved significantly under riluzole (P = 0.002) . In three of six patients, the Tsui score improved by more than 30% with a greater 50% reduction in the head tremor/jerk subscore of the Tsui scale . These data suggest that riluzole may be helpful in a subgroup of patients with disabling CD refractory to other therapies . Mov Disord, 2002 Jan, 17(1), 170 - 3 Botulinum toxin antibody type A titres after cessation of botulinum toxin therapy; Dressler D et al.; In some patients, therapy with botulinum toxin type A (BT-A) becomes ineffective due to formation of antibodies (BT-A-AB) . The time course of BT-A-AB titres after cessation of BT-A therapy was quantitatively studied to determine whether and when they might drop . Thirteen patients (eight women, five men) with various dystonic syndromes and complete secondary therapy failure (CSTF) were included in this study (age at initiation of BT-A therapy, 48.2 +/- 11.3 years; number of injection series, 7.7 +/- 2.9; treatment time, 678.8 +/- 385.6 days; mean interinjection interval, 90.4 +/- 35.5 days; mean single dose, 546.7 +/- 336.9 EMU; cumulative dose, 4185.1 +/- 3375.7 EMU {1 EMU = 1 botox MU = 3 dysport MU}) . During a monitoring period of at least 750 days after occurrence of CSTF, two or more BT-A-AB tests using the quantitative mouse diaphragm assay were performed . Eight of 13 BT-A-AB titres decreased . The onset of decrease could be detected after between approximately 500 and 1,750 days . After 1,250 to 2,250 days they had dropped below a level of 0.002 U/ml, where CSTF is unlikely . Five of 13 BT-A-AB titres did not decrease . For three of these five, the monitoring period was less than 1,500 days; a chance to drop remained . The other two were monitored for up to 2,400 days . Patients with decreasing and nondecreasing BT-A-AB titres did not exhibit statistically significant differences in either clinical characteristics or treatment parameters . When BT-A therapy was stopped the majority of BT-A-AB titres eventually decreased, allowing reinitiation of BT-A therapy . Application of new BT-A preparations with low antigenic potency might then become an interesting treatment option . Mov Disord, 2002 Jan, 17(1), 162 - 9 Botulinum toxin and short-term electrical stimulation in the treatment of equinus in cerebral palsy; Detrembleur C et al.; Intramuscular botulinum toxin type A (BT-A) has been shown to reduce spasticity and to improve gait in children with cerebral palsy . To determine whether the efficacy of BT-A may be enhanced by electrical stimulation, as suggested in focal dystonia or in adult spastic patients, 12 children with dynamic foot equinus deformity were randomly assigned to two groups in a blinded, clinically controlled trial . Intramuscular BT-A into calf muscles was followed by adjuvant electrical stimulation in Group A (n = 6) but not in Group B (n = 6) . Clinical assessment and instrumented gait analysis were performed before and 1, 3, and 6 months after treatment . The combined treatment of BT-A and electrical stimulation was not superior to BT-A alone . For all patients, improvement of the clinical and gait variables occurred at 1 and 3 months after BT-A injection . Mov Disord, 2002 Jan, 17(1), 158 - 61 Secondary nonresponsiveness to botulinum toxin type A in patients with oromandibular dystonia; Adler CH et al.; Intramuscular injection of botulinum toxin type A is the treatment of choice for most cases of oromandibular dystonia . We report on five patients with oromandibular dystonia that developed secondary nonresponsiveness to botulinum toxin type A following multiple injections over a 6-year period . Hong Kong Med J, 1998 Sep, 4(3), 279 - 282 Treatment of dystonia with botulinum A toxin: a retrospective study of 170 patients; Kwan MC et al.; OBJECTIVE: Botulinum A toxin has been reported to provide excellent symptomatic relief for patients with dystonia . To analyse the treatment, complications, and outcome of patients receiving botulinum A toxin injection, the case records of 170 patients attending the Botox Clinic at the Kwong Wah Hospital from 1 December 1992 to 31 December 1996 were reviewed . Of these 170 patients, 130 (76.5%) had idiopathic hemifacial spasm, 18 (10.6%) had blepharospasm, 18 (10.6%) had spasmodic torticollis, and 4 (2.4%) had generalised or focal limb dystonia . One hundred and sixty-six (97.6%) patients were Chinese . The average dose of botulinum A toxin required for an optimal response was 14.54 U for those with hemifacial spasm, 49.64 U for those blepharospasm, and 137 U for those with spasmodic torticollis . Among patients with hemifacial spasm, 103 (81.7%) gave a good response, 21 (16.7%) gave a partial response, and there was no response in two (1.6%) patients . The corresponding figures for patients with blepharospasm were 7 (38.9%), 10 (55.6%), and 1 (5.6%), respectively, and for those with spasmodic torticollis, the figure were 6 (37.5%), 6 (37.5%), and 4 (2.5%), respectively . Complications from botulinum A toxin injection were rare (less than 10%), minor, transient, and usually dose-related . In conclusion, idiopathic hemifacial spasm was the most common type of movement disorder encountered in our Botox Clinic and botulinum A toxin injection was safe and effective in the majority of patients. Neurotoxicology, 2001 Dec, 22(6), 775 - 86 Neuromuscular transmission and muscle contractility in SNAP-25-deficient coloboma mice; Adler M et al.; Synaptosomal associated protein of 25 kDa (SNAP-25) is a cytoplasmic protein that participates in the docking and fusion of synaptic vesicles with the nerve terminal in preparation for neurotransmitter release . SNAP-25 is also a substrate for three of the seven serotypes of botulinum neurotoxin (BoNT) . Intoxication by BoNT/A, /C1 or /E results in weakness and paralysis of skeletal muscle due to cleavage of SNAP-25 (and syntaxin la in the case /C1) at discrete serotype-specific sites . To elucidate the role of SNAP-25 in muscle function in more detail, contractility and neuromuscular transmission were studied in a mutant mouse model termed coloboma . The coloboma mutation results from a contiguous deletion of 1-2 centiMorgans on chromosome 2, which includes the entire SNAP-25 locus and three other identified genes . Homozygotes do not survive beyond gestation day 6; heterozygotes (Cm/+) have a normal life-span but express reduced levels of SNAP-25 mRNA and protein in the brain . The consequences of the Cm/+ mutation on twitch and tetanic tension, quantal release of neurotransmitter and spinal motoneuron expression of SNAP-25 were examined in the present study . Contrary to expectations, Cm/+ mice exhibited no alteration in twitch tension and generated normal tetanic tension even at the highest frequency examined (800 Hz) . Microelectrode recordings revealed that MEPP amplitude and frequency were both within control limits . The ventral spinal cord of Cm/+ mice showed no deficiency in SNAP-25 content and immunohistochemical examination of nerve terminals in Cm/+ mice disclosed that SNAP-25 levels and distribution were similar to those of control mice . It is concluded that spinal motor neurons up-regulate SNAP-25 to preserve vital neuromuscular function. Biochemistry, 2002 Feb 12, 41(6), 1717 - 23 Arg(362) and Tyr(365) of the botulinum neurotoxin type a light chain are involved in transition state stabilization; Binz T et al.; The botulinum neurotoxin type A (BoNT/A) light chain (LC) acts as zinc endopeptidase . The X-ray structure of the toxin demonstrated that Zn(2+) is coordinated by His(222) and His(226) of the Zn(2+) binding motif HisGluXXHis and Glu(261), whereas Glu(223) coordinates the water molecule required for hydrolysis as the fourth ligand . Recent analysis of a cocrystal of the BoNT/B LC and its substrate synaptobrevin 2 suggested that Arg(362) and Tyr(365) of the homologous BoNT/A may be directly involved in catalysis . Their role and that of Glu(350) which is also found in the vicinity to the active site were analyzed by site-directed mutagenesis . Various replacements of Arg(362) and substitution of Tyr(365) with Phe resulted in 79- and 34-fold lower k(cat)/K(m) values, respectively . These changes were provoked by decreased catalytic rates (k(cat)) and not by alterations of ground state substrate binding as evidenced by largely unchanged K(d) and K(m) values . None of these mutations affected the overall secondary structure or zinc content of the LC . These findings suggest that the guanidino group of Arg(362) and the hydroxyl group of Tyr(365) together accomplish transition state stabilization as was proposed for thermolysin, being the prototypical member of the gluzincin superfamily of metalloproteases . Mutation of Glu(350) dramatically diminished the hydrolytic activity which must partly be attributed to an altered active site fine structure as demonstrated by an increased sensitivity toward heat-induced denaturing and a lower Zn(2+) binding affinity . Glu(350) apparently occupies a central position in the active site and presumably positions His(222) and Arg(362). Tidsskr Nor Laegeforen, 2001 Nov 20, 121(28), 3277 - 80 {Botulinum toxin A--effect on spasticity}; Smedal T et al.; BACKGROUND: Severe spasticity may lead to problems of movement and function, pain and hygiene, and may be difficult to treat . A team of neurologists and physiotherapists evaluated the effect of botulinum toxin A (BTX-A) on spasticity . MATERIAL AND METHODS: Ten patients with central nervous disorders were included in this study . Function, pain and personal hygiene were assessed before and after injections with BTX-A . RESULTS: Nine patients experienced improvement of function and/or pain relief . One patient had improved perception in his hand, and one patient needed only two injections to stop a vicious circle . The effect varied from patient to patient . It seemed that patients with some preserved motor control in the spastic limb could use it to learn more appropriate movement strategies . INTERPRETATION: We recommend that doctors and physiotherapists work together to identify muscle groups that need to be targeted for injection and evaluate consequences of the treatment . Injections with BTX-A should be combined with physiotherapy. Expert Opin Pharmacother, 2001 Dec, 2(12), 1985 - 94 Botulinum toxin for the treatment of cervical dystonia; Tintner R et al.; Cervical dystonia (CD) manifests clinically through involuntary spasms of neck muscles, producing abnormal head and neck movements and postures, which is often associated with pain . CD is the most common form of focal dystonia presenting to movement disorders clinics . Chemodenervation with botulinum toxin (BTX) has become the first-line treatment for CD, producing satisfactory relief of symptoms in > 80% of cases . Unresolved issues that may impact on the overall results include the method of selection for injection sites (clinical vs . electromyography), dosing, dilution and the role and relative efficacy of the different BTX serotypes . A guiding therapeutic principle of BTX injections is to achieve optimal results with the lowest possible dosage and frequency of administration . This strategy is critical in order to keep the risk of immunoresistance at a minimum . Development of antibodies that block the effects of BTX, usually associated with frequent injections of high doses, is the main reason for secondary unresponsiveness to this treatment . Although the mechanism of denervation at the neuromuscular junction by BTX is relatively well understood, the role of changes in muscle spindles and myopathic pain mechanisms, as well as secondary changes at the level of the basal ganglia, thalamus and cortex and their role in response to BTX, all need further exploration. Expert Opin Pharmacother, 2001 Oct, 2(10), 1649 - 54 Review of botulinum toxin type A and its clinical applications in migraine headache; Silberstein SD; Botulinum toxin type A (BTX-A) has been used successfully for many disorders related to excessive muscle contraction . It works, in part, by causing a dose-dependent, reversible muscle relaxation . BTX-A has also been used for migraine prevention . The mechanism by which BTX-A acts in migraine is probably unrelated to its effect on muscle relaxation . BTX-A may have a distinct antinociceptive mechanism, either through action on the muscle spindles or through a direct effect on the central nervous system . Several trials and case reports have demonstrated the safety and efficacy of BTX-A in migraine headache . BTX-A is distinct from other preventive medications . Adverse events (AEs) are rare and mild . BTX-A is convenient, since the dosing interval may be 3 months or longer . However, before BTX-A can be considered a first-line agent for migraine, larger studies need to be conducted to determine optimum dosing and administration sites as well as patient characteristics that are predictive of response. Facial Plast Surg, 2002 Feb, 18(1), 35 - 9 Botulinum toxin to minimize facial scarring; Sherris DA et al.; Botulinum toxin injection has been used for a variety of indications in humans, including blepharospasm and hyperfunctional facial lines . This article describes a novel formulation of botulinum toxin, which supplies immediate feedback to the injecting physician . Additionally, recent findings are described that indicate the immediate injection of botulinum toxin into the muscles underlying a wound can improve the cosmetic outcome of the facial cutaneous scar . Future applications of these findings are discussed. Acta Orthop Belg, 2001 Dec, 67(5), 475 - 80 Kinematic and kinetic evaluation of the ankle after intramuscular injection of botulinum toxin A in children with cerebral palsy; Zurcher AW et al.; Intramuscular botulinum toxin A (BTA) injection has a role in the conservative management of dynamic equinus deformity in children with cerebral palsy . The effect of BTA injection of the gastrocsoleus muscle during gait was evaluated . Eight children with hemiplegia (median age 4.4 years, range 2 to 8 years) were included in this retrospective study . Assessment included kinematic and kinetic gait analysis before and after (median 57.5 days) treatment . Postinjective kinematics showed significant improvement of ankle range of motion in the stance phase of gait . Ankle kinetics demonstrated a significant decrease of pathological power generation in midstance . The ankle power quotient (APQ) was also significantly improved . Ankle power in terminal stance was improved, although not to a significant level . These results provide evidence of normalization of energy production at the ankle, which is critical for normal gait . The effect of BTA is temporary and can be successfully repeated . This allows deferring the need for surgical intervention until the child is older and recurrence rate is lower. Dysphagia, 2002 Winter, 17(1), 75 - 80 Case report: botulinum toxin in hypertensive lower esophageal sphincter: a manometric case study; Lacy BE et al.; The hypertensive lower esophageal sphincter (HLES) is a disorder of esophageal motility associated with dysphagia and chest pain . Although well characterized manometrically, opinions differ greatly with regard to its pathophysiology and its management . Therapy is limited to a few medications, esophageal dilatation, and even surgery, although none of these options are consistently successful . In this case report we describe a 54-year-old woman with HLES and dysphagia who was successfully treated with botulinum toxin injection of the lower esophageal sphincter (LES) . Esophageal manometry after botulinum toxin therapy revealed normalization of LES pressures . Three months after therapy, symptoms returned and repeat esophageal manometry demonstrated the return of elevated LES pressures . This report is the only published case of botulinum toxin injection into the LES with both pre- and post-treatment esophageal manometric data . This case report is evidence that LES dysfunction produces symptoms in patients with HLES, and that reduction in LES pressure improves symptoms . Current pathophysiologic hypotheses for HLES-associated dysphagia and its treatment are briefly reviewed in this report. Facial Plast Surg, 1999, 15(3), 255 - 62 Botox for rejuvenation of the periorbital region; Frankel AS; Botulinum toxin (Botox) has become accepted as a unique and effective agent for treating various aesthetic concerns . The periorbital anatomy is particularly well suited for Botox treatments and is the most frequent site to benefit from the cosmetic application of the toxin . Therapy is aimed at paralyzing specific muscles in order to reverse their effects on the overlying skin . Cosmetic benefits of Botox treatment include smoother, line-free skin, improved brow contour, and optimal post surgical healing in certain circumstances . Botox therapy is simple, effective, and forgiving, making it very popular among physicians and patients alike . This chapter provides a review of botulinum toxin and practical information regarding its use for aesthetic application in the periorbital region. J Oral Maxillofac Surg, 2002 Feb, 60(2), 157 - 62 Surgical and nonsurgical treatment options in patients with movement disorders of the platysma; Laskawi R et al.; PURPOSE: Movement disorders of the platysma may constitute both an aesthetic and a functional problem for the affected patients, who almost always have hyperkinesis . This article describes the different treatment options for movement disorders of the platysma . PATIENTS AND METHODS: The therapeutic options that we used involved surgical and nonsurgical strategies (33 patients), including neurectomy of the cervical branch of the facial nerve, myectomy of the platysma, and the injection of botulinum toxin A . After therapy, patients were evaluated through self-assessment of the clinical outcome, clinical examination, and electromyography . RESULTS: All patients showed improvement or complete alleviation of their symptoms . The data also showed that resection of the cervical branch of the facial nerve after its anterograde neurolysis may be performed during facial nerve reconstruction . CONCLUSIONS: The various nonsurgical and surgical strategies are suitable for the treatment of different forms of platysmal movement disorders . J Laparoendosc Adv Surg Tech A, 2001 Dec, 11(6), 351 - 9 Minimally invasive surgery for esophageal achalasia; Zaninotto G et al.; BACKGROUND: Esophageal achalasia is characterized by loss of peristaltic activity and failure of relaxation of the lower esophageal sphincter (LES) . The characteristic dysphagia may be alleviated by surgery, dilations, or botulinum toxin injections . Video-endoscopic surgery is used increasingly . PATIENTS AND METHODS: This paper reports our experience with 142 consecutive achalasia patients treated by laparoscopic Heller myotomy and Dor antireflux fundoplication and followed for a median 26 months . RESULTS: Overall, the actuarial lifetable analysis showed a 90% probability of a patient's being symptom free over a 5-year period . Radiologic assessment showed a significant reduction in esophageal diameter and manometry a significant reduction in the resting tone and residual pressure of the LES . Twenty-four-hour pH monitoring showed postoperative reflux in 6.7% of patients . Persistent dysphagia or chest pain (i.e., failure of treatment) were reported by 15 patients (10.6%): 14 of them were subsequently treated with multiple pneumatic dilations, which were successful in 12 cases . CONCLUSION: Laparoscopic Heller myotomy with Dor fundoplication is a feasible and effective treatment for achalasia, with an actuarial success rate of 90% at 5 years . With additional dilation, a 98% success rate can be achieved. J Neurosci Res, 2002 Feb 1, 67(3), 321 - 8 Preferential initiation of PC12 neurites in directions of changing substrate adhesivity; Murnane AC et al.; When PC12 cells are grown on substrates showing a gradient of nonspecific adhesion, they preferentially initiate neurites in directions of changing adhesivity, whether that change is in the direction of increasing or decreasing adhesivity . This preference for changing adhesivity is ablated both by C . difficile toxin A, which inhibits all Rho-family GTPases, and by C . botulinum C3 exoenzyme, which specifically inhibits Rho . Skin Therapy Lett, 2001 Dec, 6(13), 1 - 2 Update on the botulinum neurotoxins; Carruthers A et al.; The botulinum neurotoxins (BTX) are an exciting group of therapeutic agents with dramatically expanding clinical indications . The US FDA has approved BOTOX (BTX-A, Allergan) and Myobloc (BTX-B, Elan Pharmaceuticals) for the treatment of cervical dystonia . TPP Canada has also approved BOTOX for the treatment of glabellar frown lines . The US FDA is expected to approve this new indication before the end of 2002 . These changes will dramatically expand the marketing of BTXs . Concerns about risks and side-effects diminish as clinical experience increases with this "most poisonous of poisons" . In particular, the incidence of secondary resistance to the toxin's effect has been dramatically diminished with the reduction of the non-toxic protein in current batches of BOTOX. Hum Gene Ther, 2002 Jan 20, 13(2), 225 - 32 Adenoviral retrograde gene transfer in motoneurons is greatly enhanced by prior intramuscular inoculation with botulinum toxin; Millecamps S et al.; Retrograde axonal transport of recombinant adenoviral vectors has been used successfully to deliver genes to motoneurons in rodents after injection of the vectors into muscles . However, only a small proportion of motoneurons take up and retrogradely transport adenoviral particles, limiting the value of this gene delivery method for the treatment of motor neuron diseases (MNDs) . Here we validate a new pharmacological approach for enhancing motoneuronal gene transfer after intramuscular injection of recombinant adenoviruses . We injected botulinum neurotoxin A (BoNT) into muscles of normal C57BL/6 mice and transgenic mice expressing the G93A mutation in the superoxide dismutase 1 gene (SOD1-G93A mutation, a model of amyotrophic lateral sclerosis) several days before inoculation with adenoviruses . Treatment with BoNT significantly enhanced gene transfer to motoneurons innervating the injected muscles . Modifications in motoneuron transduction appear to be a consequence of toxin-induced nerve sprouting at the end plates . These findings have major implications for devising protocols for preclinical and clinical studies using intramuscular injection of retrogradely transported gene vectors. Neurol Sci, 2001 Aug, 22(4), 303 - 6 Sporadic failure of botulinum toxin treatment in usually responsive patients with adductor spasmodic dysphonia; Galardi G et al.; Botulinum toxin (BT) injections into vocalis (thyroarytenoid) muscle is currently considered the first-choice treatment for adductor spasmodic dysphonia, producing improvement for an average period of 3 months . In our experience, sporadic failure of BT efficacy can occur even in patients usually responsive to this therapy . The reasons for these episodes have not been clarified . In a retrospective, open trial, we investigated the effect toxin preparation (Botox or Dysport) and injection monitoring (electromyography or laryngoscopy) on the success rate of BT treatment . We studied 15 patients with adductor dysphonia usually responsive to BT therapy . BT was administered into the vocalis muscle in 112 and 36 injections under electromyographic or laryngoscopic guidance, respectively . Botox and Dysport were used in 106 and 42 sessions, respectively . In 29% of all injections, no subjective or objective changes, nor side effects were observed . Failure rate did not differ using electromyographic (28.6%) or laryngoscopic (30.5%) guidance . Failure rates with Botox and Dysport were 30.2% and 26.2%, respectively, but this difference was not statistically significant . These data suggest that treatment failure may occur regardless of the method of injection and of the drug preparation used, possibly due to mislocalisation of vocal folds. Am J Phys Med Rehabil, 2002 Jan, 81(1), 66 - 7 The interosseous twitch: treatment with botulinum toxin; Ramos RD et al.; We present an 18-yr-old softball player who underwent surgery for a glenoid labrum tear and subsequent placement of a pain catheter pump . One month after withdrawing the catheter, the patient developed uncontrollable movements of her fourth digit . Neurology did not think it was a true dystonia but administered multiple medications without any relief of her symptoms . Upon referral, it was thought there was isolated contraction of the fourth dorsal and second volar interosseous muscle that was causing her finger to twitch back and forth in the plane of her hand; botulinum toxin was injected into these two muscles with complete resolution of her symptoms and pain. Clin Orthop, 2002 Jan, (394), 177 - 85 Repeated botulinum toxin A injections in the treatment of spastic equinus foot; Metaxiotis D et al.; Equinus foot disorder is a common problem for patients with cerebral palsy who are able to ambulate . Botulinum toxin A is a recommended method of treatment for temporary reduction of muscle tone . The efficacy of repeated botulinum toxin A injections in the calf muscles was evaluated in a clinical trial involving 21 children with cerebral palsy and dynamic equinus foot deformity who were able to ambulate . The mean age of the children was 5.7 years . All patients received at least two injections, six patients received at least three injections, and three patients received four injections . The outcome was evaluated using observational and three-dimensional instrumented gait analysis . Significant improvements of the gait parameters were observed at 6 and 18 weeks after the first and second injections . Botulinum toxin A injections in gastrocnemius and soleus muscles may change the natural history of equinus foot deformity in patients with spastic diplegia . Orthopaedic surgery may be postponed or avoided. Neurology, 2002 Jan 22, 58(2), 246 - 9 Botulinum toxin-induced paralysis of frontotemporal muscles improves seizure focus localization; Eisenschenk S et al.; BACKGROUND: Scalp EEG localization of epileptic foci may be obscured by electromyographic (EMG) artifact produced by ictal contraction of cranial muscles . Injection of botulinum toxin type A (BTX-A) into frontotemporal scalp muscles reduces EMG activity . Initial scalp video-EEG monitoring in three patients suggested partial seizures, but definitive lateralization or localization was precluded by EMG artifact . METHODS: EMG-guided BTX-A injection to bilateral frontotemporal muscles was performed . When artifact persisted, BTX-A administration was selectively repeated . Patients subsequently underwent scalp video-EEG monitoring 1 week later . RESULTS: All patients had reduction of EMG artifact during subsequent scalp video-EEG monitoring . No patient had adverse effects after BTX-A administration . All three patients had localization to either frontal or temporal lobes and definitive lateralization . Two of the three patients were able to proceed to invasive placement of frontotemporal subdural grid electrodes based on the BTX-A scalp video-EEG localization, and the third patient was determined to have a multifocal seizure disorder . CONCLUSIONS: Paralysis of frontotemporal scalp muscle after BTX-A administration reduces EMG artifact and may improve localization and lateralization of a seizure focus, providing a noninvasive technique for advancement toward epilepsy surgery. Laryngoscope, 2002 Jan, 112(1), 82 - 6 Botulinum toxin to reduce saliva flow: selected indications for ultrasound-guided toxin application into salivary glands; Ellies M et al.; OBJECTIVES/HYPOTHESIS: The study investigates the effect of local injections of botulinum toxin type A (Botox) into the major salivary glands of the head in various states of hypersalivation . In particular, we studied pathological states with permanent as well as passing hypersalivation disorders and present new indications for local application of botulinum toxin to the salivary glands . STUDY DESIGN: Retrospective clinical investigation . METHODS: A total of 55 to 65 units of Botox were injected under sonographic control into the left and right parotid and submandibular glands of four patients with hypersalivation resulting from head and neck carcinoma, tracheostomy, and "idiopathic" hypersalivation disorder . At defined time intervals following injection, flow rate, total protein and immunoglobulin A content, and the enzymatic activities of amylase, acid phosphatase, and kallikrein were determined in the saliva . The patients were clinically examined to assess the severity of their symptoms, including sonographic control of the major salivary glands . RESULTS: All four patients reported distinct improvement of their symptoms within 1 week after injection . Salivary flow rate had considerably dropped, whereas the concentrations of the salivary components were much increased . Sonography did not reveal any changes of the salivary gland parenchyma . Therapeutic side effects were absent . CONCLUSIONS: Treatment of hypersalivation by local injections of Botox into the salivary glands of the head is a reliable and efficient therapy without side effects for certain otolaryngological diseases, especially if injections are performed under sonographic control . Extension of this therapeutic concept to other indications is suggested. Laryngoscope, 2002 Jan, 112(1), 73 - 81 Clinical study of botulinum-A toxin in the treatment of sialorrhea in children with cerebral palsy; Suskind DL et al.; OBJECTIVE: To assess the safety and efficacy of intraglandular (parotid and submandibular) botulinum-A toxin (BTX-A) in the treatment of sialorrhea in children with cerebral palsy (CP) . STUDY DESIGN: Prospective, open-label, dose-escalation study . SETTING: Tertiary care Children's Hospital . PATIENTS: Twenty-two subjects between 8 and 21 years of age with CP and significant sialorrhea . INTERVENTION/TECHNIQUE: The first 12 subjects were injected in only the submandibular gland and the second 10 in the submandibular and parotid glands . Injections were performed under ultrasound localization . The first group (divided into 3) received a total of 10, 20, or 30 units of BTX-A . The second group (divided into 3) received a standard of 30 units in the submandibular gland and 20, 30, or 40 units in the parotid glands . MAIN OUTCOME MEASURE(S): Drool quantification using a pre- and postinjection "drool rating scale," dental roll weights, and "drool quotient." Swallowing was evaluated pre- and postinjection with a formal speech therapy evaluation . RESULTS: All subjects successfully underwent BTX-A injections without local or systemic complications . There were no adverse effects on swallowing . Objective "drool quantification" with dental rolls was extremely difficult in this population . Most indicative of results was the "drool rating" questionnaire and the "drool quotient." CONCLUSIONS: BTX-A is a potentially safe and promising, minimally invasive treatment for sialorrhea in children with cerebral palsy. Br J Ophthalmol, 2002 Jan, 86(1), 43 - 6 Botulinum toxin treatment for hyperlacrimation secondary to aberrant regenerated seventh nerve palsy or salivary gland transplantation; Keegan DJ et al.; AIM: To investigate the potential of botulinum toxin A for treating hyperlacrimation . METHODS: Three patients with unilateral symptoms of hyperlacrimation (diagnosed as "crocodile tearing") and one patient with a submandibular salivary gland transplant (SMGT) were studied . Tear production was quantified in the resting and stimulated (chewing or following exercise) state, using Schirmer's test and tear clearance . Lacrimal scintigraphy was used to assess outflow . Intraglandular injections (for patients with "crocodile tears") or periglandular injections (for the SMGT patient) of Dysport were administered in divided doses . RESULTS: Two of the three eyes with reported gustatory lacrimation had a higher Schirmer test result than their fellow eye following gustatory stimulation . Scintigraphy, with and without stimulation, confirmed a patent drainage system in these patients . The other patient demonstrated a functional obstruction to tear flow . After treatment patients with confirmed gustatory lacrimation and the SMGT patient had a marked reduction in tearing at 2 weeks . This effect lasted 3-4 months . There was no demonstrable improvement in the patient with epiphora secondary to functional obstruction . Two patients who had received intraglandular injections developed a ptosis, which resolved spontaneously . CONCLUSIONS: This study illustrates that gustatory lacrimation is a difficult diagnosis . In post-facial nerve palsy a functional element must always be considered . However, in confirmed hyperlacrimation botulinum toxin treatment is effective but side effects may occur. Ophthalmologe, 2001 Dec, 98(12), 1169 - 75 {Therapy of abducens nerve paralysis}; Kolling GH; BACKGROUND: In cases of unilateral paralyses of a lateral rectus, different operative procedures are recommended in the literature . Six typical cases are presented in this paper . METHODS AND RESULTS: Fourteen days after neurosurgical transsection of the abducens nerve, no restriction of abduction was found . The transposition procedure according to Hummelsheim was performed with good results . In three long-standing cases, botulinum toxin was used to ameliorate the contracture of the tight medial rectus muscle . In all cases no limitation of abduction was found intraoperatively, making the transposition procedure much easier to perform . In another complicated case, a unilateral recession/resection procedure was carried out . The postoperative alignment was good, but the motility and the useful field of binocular vision were restricted . In the last case, the absent function of the lateral muscle was restored using a silicon rod fixed in the lateral wall of the orbit . The field of binocular single vision ranged from 12 degrees adduction to 23 degrees abduction 3 months after operation . CONCLUSIONS: Second operations are easy to perform on completely transposed muscles and in cases of recession/resection procedures, but not easy nor predictable after Hummelsheim operations . Botulinum toxin is a useful adjunct in cases of sixth nerve paralyses. J Neurol Neurosurg Psychiatry, 2002 Feb, 72(2), 249 - 56 Pallidal deep brain stimulation in patients with cervical dystonia and severe cervical dyskinesias with cervical myelopathy; Krauss JK et al.; OBJECTIVES: Surgical treatment of complex cervical dystonia and of cervical dyskinesias associated with cervical myelopathy is challenging . In this prospective study, the long term effect of chronic pallidal stimulation in cervical dystonia and on combining the technique with spinal surgery in patients with severe cervical dyskinesias and secondary cervical myelopathy is described . METHODS: Eight patients with a history of chronic dystonia who did not achieve adequate benefit from medical treatment or botulinum toxin injection participated in the study . Five patients had complex cervical dystonia with tonic postures and phasic movements . Three patients had rapidly progressive cervical myelopathy secondary to severe cervical dyskinesias and dystonia in the context of a generalised movement disorder . Quadripolar electrodes were implanted in the posteroventral lateral globus pallidus internus with stereotactic CT and microelectrode guidance . In the three patients with secondary cervical myelopathy, spinal surgery was performed within a few weeks and included multilevel laminectomies and a four level cervical corporectomy with spinal stabilisation . RESULTS: Improvement of the movement disorder was noted early after pallidal surgery, but the full benefit could be appreciated only with a delay of several months during chronic stimulation . Three months after surgery, patients with cervical dystonia had improved by 38% in the severity score, by 54% in the disability score, and by 38% in the pain score of a modified version of the Toronto western spasmodic torticollis rating scale . At a mean follow up of 20 months, the severity score had improved by 63%, the disability score by 69%, and the pain score by 50% compared with preoperatively . There was also sustained amelioration of cervical dyskinesias in the three patients who underwent spinal surgery . Lead fractures occurred in two patients . The mean amplitude needed for chronic deep brain stimulation was 3.8 V at a mean pulse width of 210 micros, which is higher than that used for pallidal stimulation in Parkinson's disease . CONCLUSIONS: Chronic pallidal stimulation is effective for complex cervical dystonia and it is a useful adjunct in patients with cervical dyskinesias and secondary cervical myelopathy who undergo spinal surgery. Can J Ophthalmol, 2001 Dec, 36(7), 398 - 403 Botulinum toxin for blepharospasm and hemifacial spasm: stability of duration of effect and dosage over time; Drummond GT et al.; BACKGROUND: Patients often ask whether the relief they experience with botulinum A toxin will diminish with time, resulting in the need for an increased dosage and more frequent administration . We performed a retrospective study to examine these questions . METHODS: We reviewed the charts of 28 patients (17 with benign essential blepharospasm and 11 with hemifacial spasm) seen between 1989 and 1994 by one ophthalmologist at the botulinum clinic at a university-affiliated hospital in Edmonton . All patients had had at least 6 botulinum A toxin treatments; 17 had had 12 or more treatments, and 7 had had 20 or more treatments . A follow-up data collection form was used to record duration of effect, dosage and side effects . We analysed the data on duration of effect and dosage versus treatment number for individual patients and for the overall group using linear regression analysis . RESULTS: There was no clinically or statistically significant change in duration of effect over time (mean slope 0.024 {95% confidence interval (CI) -0.218 to 0.266}) . A positive mean slope of 0.677 (95% CI 0.252 to 1.102) was observed for the change in dosage over time . This trend was most likely related to the practitioner's habit of using half the normal maintenance dosage for the initial injection . When we eliminated the data for the first injection and recalculated the dosage requirement over time, the mean slope for the change in dosage was 0.321 (95% CI -0.084 to 0.726), confirming stable dosage requirements over time . INTERPRETATION: The results suggest that patients can be reassured that duration of benefit and dosage requirements will likely remain stable over time for at least their first 20 treatments. Laryngorhinootologie, 2001 Dec, 80(12), 708 - 13 {Oromandibular dystonia . Clinical forms, diagnosis and examples of therapy with botulinum toxin}; Laskawi R et al.; BACKGROUND: The present study reports on our experience with clinical aspects and therapy of oromandibular dystonia (OMD) with botulinum toxin A . OMD is a very rare form of focal dystonias . The clinical symptoms can vary considerably, depending on the musculature affected . PATIENTS: The various clinical forms are described . The description of the diagnostic analysis and the therapy with botulinum toxin A is explained with reference to the patients . In these cases, injections are made into the musculature of the base of the mouth, the muscles involved in chewing, the extrinsic muscles of the tongue and the caudal facial musculature . RESULTS: Most of the patients showed an improvement of their symptoms . The average dose of Botox(R) used was 35.4+/-23.6 units . The duration of the effect was 14+/-9.2 weeks on average . CONCLUSION: The therapy for OMD using botulinum toxin A has proved to be successful, the amount of improvement in this form of dystonia is, however, lower in comparison to other forms of mobility disorders in the head and neck region. J Cell Sci, 2001 Dec, 114(Pt 24), 4397 - 405 SNAP-25 with mutations in the zero layer supports normal membrane fusion kinetics; Graham ME et al.; Considerable data support the idea that intracellular membrane fusion involves a conserved machinery containing the SNARE proteins . SNAREs assembled in vitro form a stable 4-helix bundle and it has been suggested that formation of this complex provides the driving force for bilayer fusion . We have tested this possibility in assays of exocytosis in cells expressing a botulinum neurotoxin E (BoNT/E)-resistant mutant of SNAP-25 in which additional disruptive mutations have been introduced . Single or double mutations of glutamine to glutamate or to arginine in the central zero layer residues of SNAP-25 did not impair the extent, time course or Ca2+-dependency of exocytosis in PC12 cells . Using adrenal chromaffin cells, we found that exocytosis could be reconstituted in cells transfected to express BoNT/E . A double Q-->E mutation did not prevent reconstitution and the kinetics of single granule release events were indistinguishable from control cells . This shows a high level of tolerance of changes in the zero layer indicating that the conservation of these residues is not due to an essential requirement in vesicle docking or fusion and suggests that formation of a fully stable SNARE complex may not be required to drive membrane fusion. J Voice, 2001 Dec, 15(4), 576 - 86 Longitudinal effects of botulinum toxin injections on voice-related quality of life (V-RQOL) for patients with adductory spasmodic dysphonia; Hogikyan ND et al.; Adductory spasmodic dysphonia is a focal dystonia of laryngeal muscles . Patients with this disorder typically have severe vocal difficulties, with significant functional, social, and emotional consequences . There is no widely accepted cure for this condition, however, botulinum toxin injections of the thyroarytenoid muscles are considered by most voice clinicians to be the state of the art treatment . Based on extensive experience treating patients for adductory spasmodic dysphonia, we feel that traditional means of voice assessment do not adequately measure either the disease severity or the treatment outcomes . That is, listening to or acoustically analyzing limited phonatory samples does not capture the functional, social, and emotional consequences of this disorder . These consequences will be reflected in a patient's voice-related quality of life (V-RQOL) . Using a validated voice outcomes instrument, the V-RQOL Measure, the purpose of this study was to quantify longitudinal changes in the V-RQOL of patients with adductory spasmodic dysphonia who are undergoing botulinum toxin injections . Twenty-seven consecutive new patients presenting with dysphonia to our institution during an 18-month period were diagnosed with adductory spasmodic dysphonia, and treated patients were evaluated prospectively using the V-RQOL Measure . Results indicated that (1) V-RQOL was initially very low for these patients, (2) botulinum toxin injections improved it significantly for each injection cycle studied, and (3) the magnitude of the treatment effect appears to change across injections. Prostaglandins Other Lipid Mediat, 2002 Jan, 67(1), 27 - 30 Latanoprost in hemifacial spasm; Crevits L et al.; An empirical observation that the prostaglandin derivate latanoprost quited facial spasms in patients with glaucoma prompted us to study latanoprost in non-glaucomatous patients with hemifacial spasms {HFS} . This explorative trial followed an open-label, prospective treatment design . At short term, most patients showed no or only mild improvement and subsequently needed therapy with Botulinum toxin A . Although these results are not impressive, latanoprost could be considered as an interesting alternative in the treatment of patients with HFS and with concomitant glaucoma . A role for prostaglandins in the trigeminofacial reflex is hypothesised. Ann Thorac Surg, 2001 Dec, 72(6), 1909 - 12; discussion 1912-3 Outcomes after minimally invasive esophagomyotomy; Luketich JD et al.; BACKGROUND: Thoracic surgeons traditionally performed thoracotomy and myotomy for achalasia . Recently minimally invasive approaches have been reported with good success . This report summarizes our single-institution experience using video-assisted thoracoscopy (VATS) or laparoscopy (LAP) for the treatment of achalasia . METHODS: A review of 62 patients undergoing minimally invasive myotomy for achalasia was performed . There were 27 male and 35 female patients . Mean age was 53 years (range 14 to 86) . Thirty-seven (59.7%) had failed prior treatments (balloon dilation, botulinim toxin injection, or prior surgery) . Outcomes studied were dysphagia score (1 = none, 5 = severe), Short-Form 36 quality of life (SF36 QOL) score, and heartburn-related QOL index (HRQOL) . RESULTS: Surgery included myotomy and partial fundoplication (5 VATS and 57 LAP) . Mortality was zero, and complications occurred in 9 (14.5%) patients . There were 6 perforations (4 repaired by LAP and 2 open) . Median length of stay was 2 days, time to oral intake was 1 day . At a mean of 19 months follow-up, 92.5% of patients were satisfied with outcome . Dysphagia scores improved from 3.6 to 1.5 (p < 0.01) but 3 patients ultimately required esophagectomy for recurrent dysphagia . HRQOL scores for heartburn and SF-36 QOL scores were comparable with control populations . CONCLUSIONS: Minimally invasive myotomy and partial fundoplication for achalasia improved dysphagia in 92.5% of patients with heartburn and QOL scores were comparable with normal values at 19-month follow-up . The laparoscopic approach offers excellent results and was the preferred approach by our thoracic group for treating achalasia . Thoracic residency training should strive to include laparoscopic esophageal experience. Rev Neurol (Paris), 2001 Sep, 157(8-9 Pt 2), 1051 - 9 {Genital and sphincter disorders}; Joseph PA et al.; Symptomatic bladder dysfunction occurs at some time in most patients with multiple sclerosis . Detrusor hypereflexia and sphincter dyssynergia are the main dysfunctions . Anticholinergic medication is currently the most effective and the most common treatment of overactive bladder with reduced bladder capacity and uninhibited detrusor contractions . Desmopressin, surgery, permanent indwelling catheter or external device are used in some cases . Nevertheless essential to bladder management is understanding to what extent the patient has incomplete emptying while complaining predominantly of symptoms of detrusor overactivity: frequency and urgency, with or without urge incontinence . Intravesical capsaicin and botulinum toxin injected into the detrusor seems promising means of treating intractable bladder hyperreflexia . If the post-micturition residual volume is raised, intermittent self-catheterization is the most adequate method to achieve bladder emptying of patients with MS . Physical and cognitive disability as well as patients motivation can reduce their ability to perform catheterization . In such situation, alphablockers show moderate efficacy and botulinum toxin urethral sphincter injection or surgical solution may be discussed . Disturbed anorectal physiology is common in MS, but there are as yet few specific treatments . The efficacy of oral sildenafil for treatment of neurogenic erectile failure increases the range of treatment available for men with sexual dysfunction . In women, mechanical remedies, treatment of motor and sensory loss are effective for dyspareunia . Patients of both sexes are likely to welcome to discuss their problem, and counselling or psychotherapy may be of use. Rev Neurol (Paris), 2001 Sep, 157(8-9 Pt 2), 1041 - 4 {Spasticity and multiple sclerosis}; Bussel B et al.; Spasticity is a common symptom in MS patients . It is easy to recognize and evaluate spasticity at rest . The efficacy of numerous treatments has been well documented . Nevertheless, it is difficult, particularly in MS patients, to assess the functional disability due to spasticity and the functional benefit due to treatment . This is why it is appears more appropriate to use therapeutic tests with transitory effects such as anesthetic blocks in case of focal spasticity or intrathetical baclofen in case of diffuse spasticity . It is also possible to use reversible treatments such as botulinum toxin injections before proposing section of a peripheral nerve. Biopolymers, 2002 Mar, 63(3), 168 - 80 Molecular dynamics simulations of alpha2 --> 8-linked disialoside: conformational analysis and implications for binding to proteins; Vasudevan SV et al.; Computational methods have played a key role in elucidating the various three-dimensional structures of oligosaccharides . Such structural information, together with other experimental data, leads to a better understanding of the role of oligosaccharide in various biological processes . The disialoside Neu5Ac-alpha2-->8-Neu5Ac appears as the terminal glycan in glycoproteins and glycolipids, and is known to play an important role in various events of cellular communication . Neurotoxins such as botulinum and tetanus require Neu5Ac-alpha2 --> 8-Neu5Ac for infecting the host . Glycoconjugates containing this disialoside and the enzymes catalyzing their biosynthesis are also regulated during cell growth, development, and differentiation . Unlike other biologically relevant disaccharides that have only two linkage bonds, the alpha2-->8-linked disialoside has four: C2-O, O-C8', C8'-C7', and C7'-C6' . The present report describes the results from nine 1 ns MD simulations of alpha2-->8-linked disialoside (Neu5Ac-alpha2-->8-Neu5Ac); simulations were run using GROMOS96 by explicitly considering the solvent molecules . Conformations around the O-C8' bond are restricted to the +sc/+ap regions due to stereochemical reasons . In contrast, conformations around the C2-O and C8'-C7' bonds were found to be largely unrestricted and all the three staggered regions are accessible . The conformations around the C7'-C6' bond were found to be in either the -sc or the anti region . These results are in excellent agreement with the available NMR and potential energy calculation studies . Overall, the disaccharide is flexible and adopts mainly two ensembles of conformations differing in the conformation around the C7'-C6' bond . The flexibility associated with this disaccharide allows for better optimization of intermolecular contacts while binding to proteins and this may partially compensate for the loss of conformational entropy that may be incurred due to disaccharide's flexibility . J Neurophysiol, 2002 Jan, 87(1), 229 - 39 Adaptive changes in locomotor activity following botulinum toxin injection in ankle extensor muscles of cats; Misiaszek JE et al.; The present study investigated the adaptations made in motor behavior following a temporary reduction in ankle extensor activity in the walking cat . Temporary muscle weakness was induced by injecting botulinum toxin into the lateral gastrocnemius (LG), plantaris (PL), and soleus (SOL) muscles, or SOL alone . The medial gastrocnemius (MG) muscle was not injected . Adaptations in the level of muscle activity were recorded using chronically implanted electromyographic (EMG) electrodes . Serial recordings were made prior to botulinum toxin injections and for several days following the injections . Kinematic analysis of ankle joint movements was made from video records to assess the impact of the botulinum toxin injections on the function of the ankle joint during walking . Following injection of the LG, PL, and SOL muscles with botulinum toxin, the amplitude of the MG burst increased over a period of a few days to a week . This increase was similar to the previously reported changes produced in MG following transection of the nerves serving LG, PL, and SOL . Following the weakening of the ankle extensor muscles, there was a temporary deficit in ankle function during walking as evidenced by a marked increase in the amount of ankle flexion that occurred at stance onset . This functional deficit recovered relatively quickly and was not associated with a return of the EMG pattern to the preinjection pattern . After recovery from the initial injections, a second injection of botulinum toxin into SOL alone was performed . No functional deficits were observed in the ankle movements during walking following this second injection . However, weakening SOL produced increases in the burst amplitudes of the MG, LG, and PL muscles over a period of a few days . This suggests that normal movements at the ankle during walking can be generated with more than one pattern of ankle extensor activity and that there is flexibility in how the necessary torque is produced . A final procedure, transection of the nerves serving LG, PL, and SOL, failed to produce any functional deficits in ankle movements . The implication is that adaptations to the neural control of ankle extensor activity that were induced by the initial procedure persisted after the recovery of the injected muscles and were sufficient to compensate for the subsequent challenges. Eur J Neurol, 2001 Nov, 8(6), 567 - 71 Treatment of relative sialorrhoea with botulinum toxin type A: description and rationale for an injection procedure with case report; Glickman S et al.; This paper describes a technique for treatment of relative sialorrhoea by injection of botulinum toxin type A . It includes the rationale for treatment, a description of the regional anatomy, the physiological basis for treatment and the applied pharmacology of the drug . Included also is a case report which is intended to provide an illustration of the benefits of using this method for treating this condition. Eur J Neurol, 2001 Nov, 8(6), 559 - 65 A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke; Bakheit AM et al.; OBJECTIVE: To study the efficacy and safety of botulinum toxin type A (BtxA) in the treatment of upper limb muscle spasticity, caused by stroke . METHODS: This was a randomized, controlled trial . Patients received either placebo injections or a total of 1000 IU of BtxA (Dysport) into five muscles of the affected arm . Muscle tone was assessed using the Modified Ashworth Scale (MAS) . Other outcome measures were the change in the joint range of motion (ROM), the Barthel index, pain score, goal attainment and the subjective evaluation of benefit by patients and investigators . The patients were assessed blind to randomization at baseline and 4, 8, 12 and 16 weeks after treatment . RESULTS: Fifty nine patients were recruited and received treatment . One patient was lost to follow-up before the last scheduled visit of the study . The group of patients who received BtxA had a significant reduction in the summed MAS score at week 4 compared with the placebo group (P=0.004) . The magnitude of benefit over the 16 week follow-up period was significantly reduced for the BtxA group in the wrist (P=0.004) and the finger joints (P=0.001) when compared with the placebo . There was no statistically significant difference between the groups in the joint ROM, muscle pain, goal-attainment or the Barthel index scores at week 4 of the study . At week 16, the BtxA group showed significantly greater improvement in the passive ROM at the elbow (P=0.036) . The patients' global assessment of benefit at the end of the study showed that 16 (50%) patients in the placebo group had 'much improved' or had 'some improvement' compared with 24 (92.3%) patients in the BtxA group (P=0.007) . The investigators' rating for the same item was 16 (50%) and 23 (88.4%) patients, respectively (P=0.002) . Sixteen and twenty patients in the BtxA and placebo groups, respectively, had an adverse event . The most frequently reported adverse events were accidental injury, respiratory and urinary tract infections and muscle pain . CONCLUSION: The findings of the present study suggest that treatment with BtxA in a dose of 1000 units reduces muscle tone in patients with post-stroke upper limb spasticity . This effect is sustained for at least 16 weeks . BtxA is safe in the dose used in this study . IMPORTANT NOTE: The authors wish to emphasize that the botulinum toxin preparation used in this study was Dysport (Ipsen Ltd) which has a different therapeutic equivalence from other commercially available product, Botox (Allergan Inc.). J Clin Gastroenterol, 2002 Feb, 34(2), 126 - 8 Gastrointestinal uses of botulinum toxin; Qureshi WA; Botulinum toxin was initially used in medicine to produce a potent neuromuscular blockade . It was later found to interfere with acetylcholine release in the myenteric plexus and inhibit contraction in gastrointestinal smooth muscle, leading to its use in the treatment of various conditions . It is frequently used in the treatment of achalasia in elderly patients who may be poor surgical candidates . It has been used successfully in the management of various conditions, including anal fissure and biliary dyskinesia . Large controlled trials are needed to establish the role of botulinum toxin and its safety in gastroenterology. Acta Ophthalmol Scand, 2001 Dec, 79(6), 585 - 8 Thyroid associated ophthalmopathy: botulinum toxin A in the treatment of upper eyelid retraction--a pilot study; Traisk F et al.; PURPOSE: Eyelid retraction in patients with thyroid associated ophthalmopathy is a common cause of eye discomfort and a disfigured facial appearance . The aim of this pilot study was to evaluate the effects and safety of inducing a temporary partial ptosis of the eyelid through injection of botulinum toxin A into the levator palpebrae superioris muscle . METHODS: Nine patients were treated . They were followed up with ophthalmologic examinations and self-assessment questionnaires until the point at which they either required renewed treatment or had no residual effect of the first injection . Maximum follow-up time was twenty weeks . RESULTS: In all eyes but one there was a lowering of the eyelid position one week after treatment and all these patients reported an improvement of eye appearance and symptoms . There was variability in the degree of lowering of the eyelid with the same dose of injected botulinum toxin A . It was also difficult to predict the time interval needed for re-treatment . Ptosis impairing visual acuity was not a consequence of the treatment in any of the patients . One week after treatment two patients experienced increased diplopia but only one showed transient change in Lees screen measurement of eye motility . CONCLUSION: Botulinum toxin A injection may be used to lower the upper eyelid position in patients awaiting eyelid surgery . The treatment safely relieved symptoms and improved eye appearance . However, treatment was short term and difficult to predict . There is also an inherent risk of transient diplopia. Otolaryngol Clin North Am, 2002 Feb, 35(1), 171 - 86, vii Botulinum toxin use in facial plastic surgery; Lovice D; Botulinum toxin injection into specific mimetic facial muscle beds may be used alone or in conjunction with surgical modalities to rejuvenate the aging face and neck. Clin Experiment Ophthalmol, 2001 Dec, 29(6), 394 - 9 An evaluation of the safety and efficacy of botulinum toxin type A (BOTOX) when used to produce a protective ptosis; Ellis MF et al.; PURPOSE: To evaluate the safety and efficacy of botulinum toxin type A (BOTOX, Allergan) when used to produce a protective ptosis in patients where a surgical tarsorrhaphy would otherwise be required . METHODS: A total of 21 patients entered into the study . Doses of 2.5 and 5.0 units of BOTOX were injected into the levator palpebrae superioris muscle through the eyelid . The patients were followed daily where practical until a ptosis developed and then monitored 1-2 weekly until the ptosis was resolved . Injections were repeated, if necessary until the underlying condition had healed . RESULTS: Ptosis took an average +/- SE of 4.0 +/- 0.5 days to develop (range 2-8 days) . Duration of ptosis was an average +/- SE of 46.0 +/- 12.1 days (range 1-206 days) . The effective dosage was 5 units of BOTOX in 0.1 mL . In 16 patients, the ptosis produced by BOTOX was sufficient to allow the underlying disease to heal and a surgical tarsorrhaphy was avoided . One patient required a surgical tarsorrhaphy and three patients required other surgical intervention to correct the underlying condition . One patient was lost to follow up . Diplopia was seen in five patients but resolved in all cases . CONCLUSIONS: BOTOX was a suitable alternative to a surgical tarsorrhaphy. Chin Med J (Engl), 2000 Sep, 113(9), 794 - 8 Comparison of Botox with a Chinese type A botulinum toxin; Tang X et al.; OBJECTIVE: To confirm and compare the therapeutic efficacies and remote effects of a Chinese type A botulinum toxin (CBTX-A, Lanzhou Biological Products Institute, China) and Botox (Allergan Inc., USA) for focal dystonia and muscle spasm . METHODS: Prospective open study was conducted over 4 years for focal dystonia and muscle spasm . We enrolled 785 patients: 192 were injected with Botox and 593 with CBTX-A . They were followed for 3 to 48 months . Meanwhile single fiber electromyography (SFEMG) was performed in a subset of 40 patients before, 2-3 weeks, 5-8 weeks and 4-5 months after injection of Botox or CBTX-A . RESULTS: There were no significant differences in clinical effects from two preparations, including the latency of response, maximal benefit and duration of improvement . The dose of the Chinese preparation which produced effects similar to Botox was higher . A significant increase in jitter was demonstrated 2-3 weeks after injection in both groups and fiber density values increased at the same time or later and remained 4-5 months after injections . CONCLUSION: Both preparation are safe and effective treatments for patients with focal dystonia and muscle spasm . They both have subclinical effects on neuromuscular transmission of remote uninjected muscles . The Chinese preparation is a little less powerful but much cheaper than Botox. Rev Med Chil, 2001 Oct, 129(10), 1142 - 6 {Preliminary results of laparoscopic video esophagomyotomy in patients with esophageal achalasia}; Csendes A et al.; BACKGROUND: Laparoscopic esophagomyotomy is becoming a good alternative to pneumatic dilatation, injection of botulinic toxin or classical surgery in the treatment of achalasia . AIM: To report the results of laparoscopic esophagomyotomy in patients with achalasia . PATIENTS AND METHODS: Nineteen patients with achalasia, nine women, aged 9 to 66 years old, operated between 1996 and 2001 are reported . RESULTS: There was no surgical mortality . One patient had a subphrenic abscess due to an unnoticed tear of the esophageal mucosa . During surgery, esophageal mucosa was perforated in 4 patients, that was sutured in three . One patient with an extensive tear of the mucosa required conversion to classical surgery . Patients were followed for 2 to 48 months . Radiological controls showed a significant increase in the diameter of gastroesophageal junction and a diameter reduction of the mid third esophageal segment . Lower esophageal pressure was significantly reduced . All patients experienced a weight increase and reduction of dysphagia . CONCLUSIONS: Laparoscopic esophagomyotomy is a safe an effective therapeutic alternative for achalasia. Head Neck, 2001 Dec, 23(12), 1061 - 74 Vocal process granuloma; Hoffman HT et al.; BACKGROUND: This review article reports the evolution of knowledge regarding the benign proliferations of the posterior glottis commonly termed "vocal process granuloma" . METHODS: A comprehensive review of publications addressing lesions of the posterior glottis is affected to analyze the contemporary management of vocal process granuloma . RESULTS: Contemporary management emphasizes interventions to decrease irritation to the posterior glottis . Multiple causes of this irritation preclude use of a single management plan that will successfully address all cases . CONCLUSIONS: Management to diminish laryngopharyngeal reflux, as well as to correct vocally abusive behavior, will appropriately address the majority of vocal process granuloma . Surgical removal is best reserved for cases when conservative management fails, when airway obstruction is a concern, or when a biopsy is needed to establish the diagnosis . Ancillary measures that may be beneficial in specific cases include the use of steroids, antibiotics, membranous vocal fold augmentation, and laryngeal botulinum neurotoxin injection . Expert Opin Investig Drugs, 2001 Dec, 10(12), 2191 - 9 Botulinum toxin type B: a new injectable treatment for cervical dystonia; Brashear A; Cervical dystonia (CD) causes involuntary muscle spasms and is often associated with pain . Recently, botulinum toxin type B (BTX-B) (Myobloc, Elan South San Francisco, CA, USA) was approved for general use in the treatment of CD in the USA . In two large pivotal trials, BTX-B was found to be safe and effective in decreasing the movements, pain and disability associated with CD . Benefits were noted both in patients who no longer respond and in those who continue to respond to botulinum toxin type A (BTX-A) . BTX-B offers an additional therapeutic option for patients with CD. Expert Opin Investig Drugs, 2001 Oct, 10(10), 1831 - 45 Advances in pharmacological treatment of migraine; Diener HC et al.; Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise . This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis . Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating migraine attacks . Few controlled trials were performed for the use of ergotamine or dihydroergotamine . These trials indicate inferior efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans) . The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), are highly effective . They improve headache as well as nausea, photo- and phonophobia . The different triptans show only minor differences in efficacy, headache recurrence and adverse effects . The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics . Migraine prophylaxis is recommended, when more than three attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe . Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline . Recently anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine . The use of botulinum toxin is under investigation. Expert Opin Investig Drugs, 2001 Aug, 10(8), 1531 - 44 Botulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects; Borodic GE et al.; Botulinum toxin (BTX) injections are a well-recognised therapeutic modality for the treatment of regional involuntary muscle disorders and recently BTX has been used for treatment of pain and inflammatory disorders . The primary purpose of this review is to discuss the mechanism of action of therapeutic BTX in light of both the traditional understanding of BTX pharmacological effects as well as new observations . The review will deal with clinical observations and relevant animal experimentation . The data and hypotheses presented are not only relevant to botulinum toxin technology but will certainly prove important in the basic mechanisms of some of the diseases where botulinum toxin has been successfully applied . BTX used clinically comprises botulinum neurotoxin (BoNT) complexed with non-toxic proteins . The non-toxic components of the BTX complexes stabilise the labile BoNT during purification and formulation as a therapeutic . The complex proteins may also have unrecognised clinical significance such as slowing diffusion in tissues or imparting stability . The mechanisms of BTX formulations acting on SNARE proteins are briefly reviewed providing a basis for BTX clinical applications . The potential for design of improved botulinum toxins and formulations is addressed. Drugs, 2001, 61(15), 2207 - 20 Pharmacological options for the treatment of Tourette's disorder; Jimenez-Jimenez FJ et al.; Tourette's disorder is a neuropsychiatric disorder characterised clinically by motor and vocal tics, which may be associated to conductual disorders such as obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD) . Although the neurochemistry of Tourette's disorder is not well known, there are some effective therapies for tics, OCD and ADHD . However, these are not devoid of adverse effects . Tics only require treatment when they interfere with the functioning of the patient . If therapy is needed, monotherapy at the minimal effective dose is desirable, but some patients may require two or more drugs . The most frequently used drugs for tics are antipsychotics (mainly pimozide and haloperidol) and clonidine . The potential usefulness of atypical antipsychotic drugs (risperidone, olanzapine, clozapine, ziprasidone) and other dopaminergic drugs (fluphenazine, sulpiride, tiapride, metoclopramide, piquindone, tetrabenazine), clonazepam, calcium channel antagonists, botulinum toxin, dopamine agonists, selegiline, and other drugs is discussed . The drugs of choice for OCD in patients with Tourette's disorder are the selective serotonin reuptake inhibitors (SSRIs), although the tricyclic antidepressant clomiplamine, which inhibits both serotonin and noradrenaline uptake, has also been found to be useful . ADHD can be treated with some psychostimulants, mainly methylphenidate, although these drugs must be used with caution . Other potentially useful drugs for the treatment of ADHD in patients with Tourette's disorder are clonidine, guanfacine, selegiline, some tricyclic antidepressants, sertraline, pimozide and clonazepam . Finally, the potential value of some nonpharmacological therapies (hypnotherapy, biofeedback, conductual therapies, electroconvulsive therapy, acupuncture and surgery) is briefly reviewed. Ann Otol Rhinol Laryngol, 2001 Dec, 110(12), 1162 - 4 Treatment of postparotidectomy salivary fistula with botulinum toxin; Guntinas-Lichius O et al.; We report on the successful treatment with botulinum toxin type A local injections of a salivary fistula that occurred after superficial parotidectomy . In a 58-year-old woman, transcutaneous discharge of saliva in the preauricular region had persisted in spite of 2 surgical revisions . Moreover, facial weakness and synkinesis had developed as a result of an iatrogenic lesion that had occurred at the time of primary surgery and required immediate reanastomosis of the main nerve trunk . Botulinum toxin A was injected into the deep lobe of the remaining parotid gland under ultrasonographic guidance . Additionally, botulinum toxin A was injected into the left orbicularis oculi muscle in order to improve the synkinesis . No adverse effects were observed . The sialorrhea was stopped for 11 months, and the synkinesis of the facial muscles was reduced significantly for 4 months . We conclude that botulinum toxin A injection is a successful alternative for the treatment of chronic salivary fistula. Cleve Clin J Med, 2001 Dec, 68(12), 1001 - 2, 1004-9, 1013-6 Biological and chemical terrorism: recognition and management; Noeller TP; Primary care physicians will be on the front line in detecting and managing any future terrorist attacks that use chemical or biological agents . This article reviews how to recognize and treat disease caused by exposure to nerve agents, blistering agents, hydrogen cyanide, ricin, anthrax, smallpox, plague, and botulinum toxin. Orv Hetil, 2001 Oct 21, 142(42), 2293 - 7 {Clinical symptoms, diagnosis and treatment of focal dystonias}; Klivenyi P et al.; Focal dystonias are relatively rare and significantly disabling disorders . These include cervical dystonia, blepharospasm and hemifacial spasm . The spasmodic torticollis consists of tonic posturing of the head away from its neutral position or twisting of the cervical muscles . The blepharospasm is an abnormal blinking, eyelid tic or twitch resulting from any cause . The hemifacial spasm is an involuntary unilateral twitching of the facial muscle . Patients affected by focal dystonias are predominantly females, and many times psychical stress can be revealed . The pathogenesis may involve dysfunction of the basal ganglia and brain stem although the exact mechanism remains to be elucidated . The patients need to be diagnosed and treated in centers specialized in movement disorders . Although many drug treatments can be beneficial, the most effective treatment is the local Botulinum toxin injection into the affected muscles . This neurotoxin produces temporary neuromuscular blockade, which reveals the symptoms and pain . The effect of the toxin is temporary and, therefore, the injection needs to be repeated every 6-12 weeks . The most common side effects are hypersensitivity, bleeding, hematoma, ptosis, facial spasm, dysphasia or dysarthria . With the use of proper dose and injection sites these side effects can be avoided. J Med Assoc Thai, 2001 Aug, 84(8), 1199 - 203 The first world report of botulinum A toxin injection for status migrainosus; Poungvarin N; The author reports the first ever documented publication in the world concerning the use of botulinum toxin A (BTX-A) injection for status migrainosus . A 58-year old man had been suffering from migraine without aura for 20 years . This last attack (a very severe throbbing headache) started over the left side of his head and he had tried several medications (paracetamol, aspirin, ergotamine, mefenamic acid, and diazepam) during the attack to no vail . Physical examination revealed an acutely ill patient with an agonizing pain condition . General and neurological examinations were normal . BTX-A solution was then injected into the Fung Chou point (classical Chinese acupuncture point for migraine) in the total amount of 25 international unit . Dramatic response was observed within 1 hour of injection and status migrainosus was abort within 10 hours . He was headache-free and had no further attack of migraine for another 2 months. J Am Acad Dermatol, 2002 Jan, 46(1), 62 - 5 Severe, intractable headache after injection with botulinum a exotoxin: report of 5 cases; Alam M et al.; BACKGROUND: Botulinum A exotoxin is a safe agent in common use in dermatology . Occasionally, patients receiving botulinum toxin injections report postprocedure discomfort, including headaches . OBJECTIVE: Our purpose was to estimate the rate of severe headaches occurring after injection with botulinum toxin for dermatologic indications . METHODS: We used prospective monitoring of botulinum toxin injection outcomes in a single-site, 3-dermatologist practice . There was in-office and telephone follow-up of patients experiencing severe headaches . RESULTS: Approximately 1% of patients (4/320) receiving botulinum A exotoxin injections may experience severe, debilitating headaches . These may persist at high intensity for 2 weeks to 1 month before gradually fading . CONCLUSION: Botulinum A exotoxin injection may be associated with the development of life-altering headaches . Patients should be informed of this possibility. J Physiol Paris, 2002 Jan-Mar, 96(1-2), 105 - 13 Botulinum neurotoxins: from paralysis to recovery of functional neuromuscular transmission; Meunier FA et al.; The neuromuscular junction is one of the most accessible mammalian synapses which offers a useful model to study long-term synaptic modifications occurring throughout life . It is also the natural target of botulinum neurotoxins (BoNTs) causing a selective blockade of the regulated exocytosis of acetylcholine thereby triggering a profound albeit transitory muscular paralysis . The scope of this review is to describe the principal steps implicated in botulinum toxin intoxication from the early events leading to a paralysis to the cellular response implementing an impressive synaptic remodelling culminating in the functional recovery of neuromuscular transmission . BoNT/A treatment promotes extensive sprouting emanating from intoxicated motor nerve terminals and the distal portion of motor axons . The current view is that sprouts have the ability to form functional synapses as they display a number of key proteins required for exocytosis: SNAP-25, VAMP/synaptobrevin, syntaxin-I, synaptotagmin-II, synaptophysin, and voltage-activated Na+, Ca2+ and Ca2+-activated K+ channels . Exo-endocytosis was demonstrated (using the styryl dye FM1-43) to occur only in the sprouts in vivo, at the time of functional recovery emphasising the direct role of nerve terminal outgrowth in implementing the restoration of functional neurotransmitter release (at a time when nerve stimulation again elicited muscle contraction) . Interestingly, sprouts are only transitory since a second distinct phase of the rehabilitation process occurs with a return of synaptic activity to the original nerve terminals . This is accompanied by the elimination of the dispensable sprouts . The growth or elimination of these nerve processes appears to be strongly correlated with the level of synaptic activity at the parent terminal . The BoNT/A-induced extension and later removal of "functional" sprouts indicate their fundamental importance in the rehabilitation of paralysed endplates, a finding with ramifications for the vital process of nerve regeneration. J AAPOS, 2001 Dec, 5(6), 370 - 6 Initial treatment outcomes in chronic sixth nerve palsy; Holmes JM et al.; INTRODUCTION: We conducted a prospective multi-center, nonrandomized, data-collection study of patients with chronic sixth cranial nerve palsy . We evaluated success rates with conservative nonsurgical management, botulinum toxin (botox) treatment, strabismus surgery, and a combination of botox treatment and surgery . METHODS: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American Neuro-Ophthalmology Society were invited to enroll patients with sixth nerve palsy or paresis of more than 6 months duration over a 2-year period (between March 1998 and February 2000) . The botox and surgical groups received intervention within 3 months of enrollment . Success at 6 months from enrollment was defined as absence of diplopia in primary position and no more than 10 prism diopters (pd) distance esotropia in primary position . Patients with no follow-up were excluded . RESULTS: Fifty-six eligible patients were enrolled by 33 investigators . Eighteen (32%) were traumatic in etiology, 15 (27%) were unknown (including presumed hypertensive), 14 (25%) were neoplastic, 2 (4%) were diabetic, and 7 (13%) were other . Twenty (35%) were managed conservatively without surgery, 10 (18%) with botox treatment, 19 (33%) with surgery, and 8 (14%) with a combination of botox treatment and surgery . Success at 6 months from enrollment was 15% in the conservatively managed cases, 10% with botox alone, 39% with surgery alone, and 25% with a combination of botox and surgery . CONCLUSIONS: This study demonstrates that management of chronic sixth nerve palsy and paresis remains challenging . Spontaneous recovery occurs but is uncommon . Botox treatment alone was rarely successful, and a single surgical procedure had a lower-than-expected success rate . Care should be taken in directly comparing success rates between treatment groups because of bias in patient selection. Dermatology, 2001, 203(4), 318 - 21 Treatment of idiopathic palmar hyperhidrosis with botulinum toxin . Report of 23 cases and review of the literature; Vadoud-Seyedi J et al.; BACKGROUND: Botulinum toxin represents a novel therapeutic option for idiopathic palmar hyperhidrosis . However, so far there is no consensus on the way to administer botulinum toxin in this indication . Moreover, its use is limited by severe pain during the injections, especially with subepidermal injections close to 'free nerve endings' . OBJECTIVES: To analyze the effectiveness and tolerability of intracutaneous injections of botulinum toxin after nerve blocks and to review the techniques of injections and the results reported by other groups . METHODS: Twenty-three adult patients with refractory palmar hyperhidrosis were treated with intracutaneous injections of botulinum toxin after ulnar and median nerve blocks . Patients were followed up on a monthly basis . RESULTS: In all patients botulinum toxin abolished sweating in the injected areas within 1 week . Anhidrosis lasted for 4-13 months . The intensity of pain was rated as absent (n = 13), mild (n = 8) or moderate (n = 2) . Other side effects included hematoma (n = 2) and pain consecutive to nerve block (n = 1) . DISCUSSION: Intracutaneous injections of botulinum toxin after median and ulnar nerve block represent an effective and mildly painful technique to treat palmar hyperhidrosis and may be as safe as subepidermal injections . Arch Dermatol, 2001 Dec, 137(12), 1622 - 5 Idiopathic localized unilateral hyperhidrosis: case report of successful treatment with botulinum toxin type A and review of the literature; Kreyden OP et al.; BACKGROUND: Localized unilateral hyperhidrosis (LUH) is a rare disorder of unknown origin . We describe a patient with LUH on the forearm, where a fracture was identified as a past injury . OBSERVATIONS: We treated the patient with botulinum toxin type A injections, and he was complaint free during the 6 months after treatment . In addition, the initially strong positive results of the iodine starch test (Minor sweat test) were negative in the affected region after treatment . CONCLUSIONS: This relatively new therapeutic modality already established for axillary, palmar, and plantar hyperhidrosis seems to be efficient in LUH . As the former therapeutic approaches are rather disappointing, and as botulinum toxin type A locally applied shows limited adverse effects, we think a trial of botulinum toxin type A is justified in cases of LUH, even as a first-line treatment . In addition, the literature considering localization and causes of LUH is reviewed. Mov Disord, 2001 Nov, 16(6), 1091 - 7 Spontaneously changing muscular activation pattern in patients with cervical dystonia; Munchau A et al.; The objective of this study was to determine stability of the neck muscle activation pattern in a given dystonic head position in patients with cervical dystonia (CD) . We assessed 26 patients with CD and botulinum toxin (BT) treatment failure before surgical denervation . None of them had received BT injections for at least 4 months . To relate dystonic head position to underlying neck muscle activity, we used synchronised video and poly-electromyographic (EMG) recording over a period of 10 minutes . The muscle activation pattern during constant ("stable") maximal dystonic excursions was analysed . EMG data of nine patients was excluded from the analysis, as these patients had a constantly changing head position or marked head tremor . In the remaining 17 patients, who had a fairly stable dystonic position, muscular activation patterns during the recording spontaneously changed in nine (Group A) while in eight it remained stable (Group B) . There was no significant difference in demographic variables between the two groups other than a male predominance in Group A . However, the retrospectively determined initial response to BT treatment (before BT treatment failure had occurred) was significantly worse in Group A as compared with Group B . Neck muscle activation patterns can spontaneously change in CD patients despite constant dystonic head position, implying an inherent variability of the underlying central motor program in some patients . This should be considered when BT treatment response is unsatisfactory, and should also be taken into account when interpreting results of EMG recordings of neck muscles in these patients . Mov Disord, 2001 Sep, 16(5), 934 - 7 Dynamic balance function in phasic cervical dystonia following Botulinum toxin therapy; Muller J et al.; Previous research by our group revealed normal dynamic balance function in pure tonic cervical dystonia (CD) with impaired equilibrium in phasic CD patients investigated at least 3 months following Botulinum toxin (BtxA) treatment . The current study was performed to determine whether impaired dynamic equilibrium in phasic CD is influenced by symptomatic treatment with BtxA . Dynamic balance was tested in 20 patients with phasic CD on a dynamic platform with a cylindrical curved base (stabilometer) 4 weeks following BtxA treatment . Balance was assessed by the linear displacement of the platform and the maximum amplitude of platform displacement with open and closed eyes and compared with pre-BtxA data . Despite a clinically significant BtxA-induced reduction of phasic head movements, none of the platform measures improved significantly . In addition, there was no correlation between the BtxA-induced clinical improvement and changes in any of the dynamic balance measures pre- vs . post-BtxA . In conclusion, the persistent dynamic balance impairment after effective BtxA therapy may indicate that disequilibrium in phasic CD does not simply reflect disturbed vestibular input from repetitive head oscillations, but argues in favour of different sensorimotor processing in tonic and phasic CD . Mov Disord, 2001 Sep, 16(5), 907 - 13 Treatment of dystonic clenched fist with botulinum toxin; Cordivari C et al.; Fourteen patients with "dystonic clenched fist" (three with Corticobasal Ganglionic Degeneration, seven with Parkinson's disease, and four with Dystonic-Complex Regional Pain Syndrome) were treated with botulinum toxin A (BTXA, Dysport) . The muscles involved were identified by the hand posture and EMG activity recorded at rest and during active and passive flexion/extension movements of the finger and wrist . EMG was useful in distinguishing between muscle contraction and underlying contractures and to determine the dosage of BTX . All patients had some degree of flexion at the proximal metacarpophalangeal joints and required injections into the lumbricals . The response in patients depended on the severity of the deformity and the degree of contracture . All patients had significant benefit to pain, with accompanying muscle relaxation, and palmar infection, when present, was eradicated . Four patients with Parkinson's disease and one patient with Dystonia-Complex Regional Pain Syndrome obtained functional benefit . Mov Disord, 2001 Sep, 16(5), 899 - 906 The natural history of embouchure dystonia; Frucht SJ et al.; Focal task-specific dystonias are unusual disorders of motor control, often affecting individuals who perform complex repetitive movements . Musicians are especially prone to develop these disorders because of their training regimens and intense practice schedules . Task-specific dystonia occurring in keyboard or string instrumentalists usually affects the hand . In contrast, there have been few descriptions of musicians with task-specific dystonia affecting the muscles of the face and jaw . We report detailed clinical observations of 26 professional brass and woodwind players afflicted with focal task-specific dystonia of the embouchure (the pattern of lip, jaw, and tongue muscles used to control the flow of air into a mouthpiece) . This is the largest and most comprehensively studied series of such patients . Patients developed embouchure dystonia in the fourth decade, and initial symptoms were usually limited to one range of notes or style of playing . Once present, dystonia progressed without remission and responded poorly to oral medications and botulinum toxin injection . Patients with embouchure dystonia could be separated by the pattern of their abnormal movements into several groups, including embouchure tremor, involuntary lip movements, and jaw closure . Dystonia not infrequently spread to other oral tasks, often producing significant disability . Effective treatments are needed for this challenging and unusual disorder . Endoscopy, 2001 Dec, 33(12), 1027 - 30 Self-expanding metal stents for endoscopic treatment of esophageal achalasia unresponsive to conventional treatments . Long-term results in eight patients; De Palma GD et al.; BACKGROUND AND STUDY AIMS: The successful use of self-expanding metal stents has been demonstrated in the management of malignant esophagocardial strictures . This report assesses the role stents may play in the treatment of esophageal achalasia in selected patients . PATIENTS AND METHODS: Between September 1996 and December 1997, eight patients (two men, six women; average age 67.6 years) underwent insertion of a self-expanding metal stent for management of achalasia . Previous myotomy and/or balloon dilation or injection of botulinum toxin had failed in all patients . Four nitinol coil stents and five covered Ultraflex stents, 10 cm long, were inserted, being passed through the gastroesophageal junction under mild sedation . RESULTS: Stent placement was successful and uncomplicated in all patients . Early complications were seen in five patients: chest pain (1), gastroesophageal reflux (1), proximal migration (1), and distal migration (2) . One patient underwent surgery for stent impaction in the colon . During the follow-up period of 35.5 months, on average (range 29 - 44 months), four patients experienced complications: chest pain (2), reflux esophagitis (1) and stent migration (1) . CONCLUSION: General use of self-expanding metal stents for esophageal achalasia cannot be recommended. Endoscopy, 2001 Dec, 33(12), 1007 - 17 Treatment of achalasia: botulinum toxin injection vs . pneumatic balloon dilation . A prospective study with long-term follow-Up; Allescher HD et al.; BACKGROUND AND STUDY AIMS: In patients with achalasia, intrasphincteric injection of botulinum toxin (BTX) has been suggested as an alternative regimen to balloon dilation and has been shown to be superior to placebo injection . The aim of the present study was to test the effectiveness, the long-term outcome and the cumulative costs of BTX injection in consecutive patients with symptomatic achalasia in comparison with pneumatic balloon dilation . PATIENTS AND METHODS: 37 patients, who presented with symptomatic achalasia between January 1994 and December 1996 were treated with either BTX injection (n = 23) or pneumatic dilation (n = 14) . Patients with short-term or long-term symptomatic failures of the initial procedure were treated again, either with the same or with the alternative method, depending on the initial response and on the patient's wish . Symptoms were assessed using a global symptom score (0 - 10) which was evaluated before treatment and 1 week, 1 month and then every 6 months after the treatment . In addition, body weight and recurrence of symptoms were noted and manometry was carried out before and after treatment . The patients were regularly contacted for the long-term follow-up . RESULTS: There were significant improvements in the global symptom scores of all patients treated, in both the BTX injection group (before 8.2 +/- 1.3, after 3.0 +/- 1.6) and the dilation group (before 8.3 +/- 1.1, after 2.3 +/- 1.9) . There was also a significant decrease of lower esophageal sphincter pressure after treatment in the BTX group and the dilation group . There were no significant differences with regard to overall treatment failure and long-term outcome between patients who had or had not received previous treatment . No major complications were encountered in either group . An actuarial analysis over 48 months comparing patients receiving BTX injection or balloon dilation demonstrated that after 12 months neither therapy was significantly superior . After 24 months a single pneumatic dilation was superior to a single BTX injection, and after 48 months all patients treated by BTX injection had experienced a symptomatic relapse . In contrast, 35 % of all patients treated by dilation and 45 % of patients treated successfully by dilation were still symptom-free in an intention-to-treat analysis after 48 months . When the overall costs of treatment and further treatment after recurrence were compared, dilation and BTX injection showed a similar cost-effectiveness (costs per symptom-free day) after 48 months . CONCLUSIONS: BTX injection, which can be performed in an outpatient setting, is as safe and cost-effective as balloon dilation in symptomatic achalasia . Taking into account the lower long-term efficacy of BTX injection therapy, however, it is an alternative only in a minority of older or high-risk patients. Neurology, 2001 Dec 11, 57(11), 2095 - 9 Botulinum toxin type A in primary palmar hyperhidrosis: randomized, single-blind, two-dose study; Saadia D et al.; BACKGROUND: Primary palmar hyperhidrosis is characterized by excessive sweating due to increased sympathetic cholinergic sudomotor nerve traffic to the palmar surface of the hands . Clinical studies suggest that intradermal injections of botulinum toxin are effective in the treatment of palmar hyperhidrosis . OBJECTIVES: To establish the effectiveness of intradermal botulinum toxin in reducing hyperhidrosis, to determine the most effective dose of toxin, and to examine its effect on muscle strength . METHODS: In a prospective, single blind, randomized trial, 24 patients with severe palmar hyperhidrosis received either a low (50 U) or a high dose (100 U) of botulinum toxin type A (Botox, Allergan) injected intradermally in 20 sites in each palm . RESULTS: Following injection with either dose, iodine starch test revealed a significant decrease in sweating within the first month . Six months after injection, the anhidrotic effect was still evident in two thirds of the patients in both groups . Handgrip strength was not affected with either dose but finger pinch strength, 2 weeks after the injection, decreased 23 +/- 27% with 50 U (p < 0.05) and 40 +/- 21% with 100 U (p < 0.001) . Pinch strength improved gradually but 6 months after treatment it was still 7-11% lower than at baseline . CONCLUSIONS: Both 50 and 100 U of botulinum toxin type A, injected intradermally in each hand, decreased sweating in patients with primary hyperhidrosis for at least 2 months in all the patients, and 6 months in most patients . Weakness in the intrinsic muscles of the hand was observed. Clin Neurophysiol, 2001 Dec, 112(12), 2293 - 9 The stimulus intensity modifies the blink reflex recovery cycle in healthy subjects and in blepharospasm; Sommer M et al.; OBJECTIVE: The excitability of human brainstem interneurons is measured by the blink reflex recovery cycle and is abnormal in blepharospasm . We wondered whether the results of this paradigm depend on the stimulus intensity . METHODS: We investigated the blink reflex recovery cycle in 13 healthy control subjects and in 13 patients with blepharospasm (7 of them treated with botulinum toxin) using 4 levels of stimulus intensity (5, 12, 19 and 26 mA) and two interstimulus intervals (ISIs, 150 or 250 ms) . RESULTS: In all groups the inhibition of the second R2 response was reduced with strong stimulus intensities: In controls, the inhibition of the second R2 decreased significantly (e.g . young controls, ISI 150 ms, from 89.6+/-15.6% at 5 mA to 21.9+/-49.7% at 26 mA, mean+/-standard deviation) . In patients the R2 inhibition found at 5 mA was converted in an R2 facilitation at 26 mA, irrespective of the status of treatment . In addition, the patients' results at 5 mA did not differ significantly from the controls' results at 26 mA . CONCLUSIONS: The R2 inhibition and its sensitivity to detect abnormal interneuronal excitability depend on the stimulus intensity, which may act by modifying the excitability of the R2 interneurons. Eur Radiol, 2001, 11(12), 2543 - 8 Epub 2001 May 12. CT-guided injection of botulinic toxin for percutaneous therapy of piriformis muscle syndrome with preliminary MRI results about denervative process; Fanucci E et al.; Piriformis muscle syndrome (PMS) is a cause of sciatica, leg or buttock pain and disability . The pain is usually increased by muscular contraction, palpation or prolonged sitting . The aim of our paper was to evaluate the feasibility of CT-guided percutaneous botulinic toxin (BTX) injection for the purpose of PMS treatment . Thirty patients suffering from PMS, suspected with clinical and electrophysiological criteria, after imaging examinations excluding other causes of sciatic pain, resulted positive at the lidocaine test and were treated by intramuscular injection of BTX type A under CT guidance . The follow-up (12 months) was performed with clinical examination in all cases and with MR 3 months after the procedure in 9 patients to evaluate the denervative process entity of the treated muscle . In 26 cases relief of symptoms was obtained after 5-7 days . In 4 patients an insufficient relief of pain justified a second percutaneous treatment which was clinically successful . No complications or side effects were recorded after BTX injection . The MR examination showed a signal intensity change of the treated muscle in 7 patients due to the denervative process of PM, whereas in the remaining 2 cases only an atrophy of the treated muscle was detected . Larger series are necessary to confirm these MRI preliminary results . The CT-guided BTX injection in the PMS is an emergent and feasible technique that obtains an excellent local therapeutic effect without risk of imprecise inoculation. Curr Opin Ophthalmol, 2001 Dec, 12(6), 419 - 22 Use of botulinum toxin in neuro-ophthalmology; O'Day J; Botulinum toxin produces a temporary chemical denervation, which initially was used to reduce the diplopia associated with paralytic strabismus . Subsequently, the drug was found to be effective in the management of dystonias, including hemifacial spasm and blepharospasm . More recently, there is evidence that botulinum toxin may lessen the pain associated with some movement disorders, tension headache, and migraine . The effect of botulinum toxin in temporary, but the therapeutic benefit usually is maintained even after repeated injections . The form of botulinum toxin used in clinical practice is the A serotype . Other serotypes may have a therapeutic role in the future . The mode of action and the clinical experience of botulinum toxin in neuro-ophthalmology is discussed. Neuroreport, 2001 Nov 16, 12(16), 3599 - 602 NGF induces neurite outgrowth via a decrease in phosphorylation of myosin light chain in PC12 cells; Fujita A et al.; The relationship between phosphorylation of myosin light chain (MLC) and neurite outgrowth induced by nerve growth factor (NGF) was studied in PC12 cells . Inhibitors of Rho kinase, HA-1077 or Y-27632 also induced neurite outgrowth . As already reported botulinum exoenzyme C3 which inactivates Rho protein also induced neurite outgrowth . Calyeulin A, an inhibitor of phosphatase counteracted both NGF- and C3- induced neurite outgrowth . Treatments of both NGF and C3 resulted in significant and transient decrease in phosphorylated MLC . These results suggest that NGF induces neurite outgrowth of PC12 by a transient decrease in phosphorylated MLC which is brought about by activation of MLC phosphatase via inhibition of Rho-Rho kinase pathway. Klin Monatsbl Augenheilkd, 2001 Nov, 218(11), 720 - 6 {Autologous serum for otherwise therapy resistant corneal epithelial defects - Prospective report on the first 70 eyes}; Ferreira de Souza R et al.; PURPOSE: The purpose of this prospective clinical pilot study was to evaluate the efficiency, practicability and safety of topical autologous serum for therapy resistant corneal epithelial defects . METHODS: Between November 1999 and June 2001 autologous serum therapy was applied in 70 eyes of 67 consecutive patients (age 18 to 92 {average 59 +/- 18} years) with corneal epithelial defects refractory to standard clinical treatment at the Department of Ophthalmology University Erlangen-Nurnberg . We evaluated localization, size of the defect, time until epithelial wound closure and the incidence of recurrences in relation to the clinical diagnosis . The blood was obtained by venipuncture, centrifuged and the non-diluted serum was filled in sterile bottles, kept in the + 4 (o)C refrigerator and hourly applied during daytime . Simultaneous systemic and topical medication depended on the underlying disease . RESULTS: In 45 eyes corneal epithelial defects appeared after penetrating keratoplasty but in 25 eyes corneal epithelial defects were not related to a corneal transplant . The epithelial defect had a medium length of 4.2 +/- 2.4 mm and a width of 3.0 +/- 1.8 mm . Previously, the patients had been treated with maximal topical therapy (including hyaluronic acid) for 13 +/- 11 days . Treatment with autologous serum lasted from 4 to 45 (mean 16 +/- 11) days . A complete corneal re-epithelialization was achieved in 57 of 70 eyes (81 %) after 3 to 45 (mean 15 +/- 12) days . Forty-eight of these 57 eyes (84 %) had no recurrence during a follow-up of 12 +/- 4 months . In 9 eyes (16 %) a recurrent epithelial defect occurred one or two months after initial closure . These eyes were treated successfully with a second autologous serum therapy (6 x), amniotic membrane transplantation (2 x) or repeat keratoplasty (1 x) . Thirteen eyes (19 %) without primary success of autologous serum applied for 11 to 50 days were finally treated successfully with amniotic membrane transplantation (10 x) or repeat keratoplasty (3 x) . CONCLUSION: In persistent corneal epithelium defects, autologous serum therapy can be considered as an effective and practicable therapy without adverse reactions . Especially in eyes after complicated penetrating keratoplasty the prognosis may be improved and more invasive treatment modalities such as botulinum toxin injection, amniotic membrane transplantation or (repeat) penetrating keratoplasty may be avoided . Definitive determinants for the success of this novel therapy have not been identified, yet . However, eyes with accompanying deep stromal defects do not seem to be good candidates. Pain, 2001 Dec, 94(3), 255 - 60 Botulinum toxin A for the treatment of chronic neck pain; Wheeler AH et al.; A clinical study tested the therapeutic efficacy of Botulinum toxin A (BTXA) when injected into symptomatic neck muscles after one injection session . Patients with chronic neck pain were randomly assigned to receive either a high dose of an active treatment or an injection of the same volume of normal saline . Patients were compared for 4 months using a comprehensive set of outcome measures that included the Neck Pain and Disability Scale (Spine 24 (1999) 1290) and pressure algometry (Arch Phys Med Rehabil 67 (1986) 406; Pain 30 (1987) 115; Clin J Pain 2 (1987) 207) . Analyses were consistent in showing significant benefits from the injection session; however, the effects were not specific to the group treated with BTXA . Both treatment and control groups showed a significant decline in pain and disability across time and an increased ability to withstand pressure on trigger points . The heavy incidence of adverse events in the treatment group may partly explain the absence of a treatment effect specific to BTXA . The results show that a single dose treatment without physical therapy is not effective for chronic neck pain. J Neuroimmunol, 2001 Dec 3, 121(1-2), 79 - 82 Anti-GD1a antibodies from an acute motor axonal neuropathy patient selectively bind to motor nerve fiber nodes of Ranvier; De Angelis MV et al.; Acute motor axonal neuropathy (AMAN) is associated with high titer anti-GD1a antibodies . We have found that very high titer IgG anti-GD1a antibodies (Ab) from one AMAN patient selectively bind to motor, but not sensory, nerve nodes of Ranvier . Binding is abolished by preadsorption with GD1a . Sera negative for Ab do not immunostain motor and sensory nerve roots . We have also found that botulinum toxin A (BTA), which binds to GD1a, stains both motor and sensory nerve nodes of Ranvier . Our results strongly support the pathogenetic role of anti-GD1a antibodies in AMAN . Why BTA also binds to sensory fibers still remains to be elucidated, although the different size of BTA and its specificity to other gangliosides present in sensory axons might represent important factors. Am Surg, 2001 Nov, 67(11), 1105 - 9 Videoscopic heller myotomy as first-line therapy for severe achalasia; Bloomston M et al.; To many nonsurgeons myotomy is considered an excessively invasive treatment for achalasia and has become a salvage procedure when esophageal dilation and botulinum toxin (botox) injections fail . We sought to examine our experience with videoscopic Heller myotomy to determine whether preoperative therapy predicts perioperative complications and long-term outcome . Videoscopic Heller myotomy was undertaken in 111 patients with achalasia between June 1992 and May 2000 . Intraoperative endoscopy was used in all patients . Fundoplication was used selectively for patients with large hiatal hernias or as part of repair of esophageal perforation . Patients were asked to grade their dysphagia and reflux symptoms before and after myotomy on a scale of 0 (no symptoms) to 5 (severe symptoms) . Patients were also asked to rate their outcome as excellent (no symptoms), good (greatly improved), fair (slightly improved), or poor (not improved) compared with their preoperative status . Patients were stratified on the basis of preoperative intervention (botox, pneumatic dilation, botox and pneumatic dilation, or no botox or dilation) and compared . Previous pneumatic dilation and/or botox injection had been undertaken before operation in 88 (79%) patients whereas 23 (21%) patients had no invasive preoperative therapy . The overall mean preoperative dysphagia score was 4.8+/-0.8 and mean preoperative reflux score was 3.3+/-2.1 . Groups of patients undergoing preoperative interventions were similar to those patients not undergoing preoperative interventions in terms of preoperative symptoms, dysphagia scores, and reflux scores . Postoperative complications (13%) and perforations (8%) were slightly more common in patients who had undergone preoperative botox or dilation (P = not significant) . Subjectively, operative myotomy was more difficult in patients who had preoperative botox or dilation . Patients had significant improvement in dysphagia, dysphagia score, reflux score, emesis/ regurgitation, and chest pain (P < 0.05) regardless of preoperative intervention . After myotomy patients who had never undergone botox or pneumatic dilation were less likely to have mild dysphagia compared with those with previous botox injections (30% vs 53%; P = 0.09), previous dilations (30% vs 54%; P = 0.09), or both (30% vs 59%; P = 0.04) . As well, dysphagia scores were better if no preoperative therapy had been undertaken: botox 0.8+/-1.3, dilation 1.0+/-1.4, botox and dilation 1.0+/-1.3, and no therapy 0.3+/-0.7 (P < 0.05) . Overall 97 per cent of patients stated that their symptoms were improved although more patients tended to have excellent or good outcomes if no preoperative intervention was undertaken (91%) compared with patients undergoing preoperative botox (86%), dilation (83%), or both (82%) (P = not significant) . We conclude that videoscopic Heller myotomy is safe and efficacious particularly in patients who have not undergone previous endoscopic interventions . The difference in patients' outcomes based on preoperative therapy may be related to a less difficult operation in patients who forgo endoscopic therapy and elect to undergo early myotomy . Although videoscopic Heller myotomy provides good outcomes as a salvage procedure after failed dilations and/or botox injections for achalasia we advocate it as first-line therapy in reasonable operative candidates. Am Surg, 2001 Nov, 67(11), 1059 - 65; discussion 1065-7 Laparoscopic anterior esophageal myotomy and toupet fundoplication for achalasia; Heniford BT et al.; Achalasia is an esophageal motility disorder characterized by the failure of lower esophageal sphincter relaxation and the absence of esophageal peristalsis . The purpose of this study was to evaluate the clinical outcomes of patients undergoing laparoscopic esophageal myotomy and Toupet fundoplication for achalasia . A 9-cm myotomy was performed in most cases extending 7 cm above and 2 cm below the gastroesophageal junction . Severity of dysphagia, heartburn, chest pain, and regurgitation was graded preoperatively and postoperatively using a five-point symptomatic scale (0-4) . Patients also graded their outcomes as excellent, good, fair, or poor . Between December 1995 and November 2000 a total of 49 patients (23 male, 26 female) with a mean age of 44.3 years (range 23-71 years) were diagnosed with achalasia . Mean duration of symptoms was 40.2 months (range 4-240 months) . Thirty-seven patients (76%) had had a previous nonsurgical intervention or combinations of nonsurgical interventions {pneumatic dilation (23), bougie dilation (five), and botulinum toxin (19)}, and two patients had failed esophageal myotomies . Forty-five patients underwent laparoscopic esophageal myotomy and Toupet fundoplication . Two patients received laparoscopic esophageal myotomies without an antireflux procedure, and two were converted to open surgery . One patient presented 10 hours after a pneumatically induced perforation and underwent a successful laparoscopic esophageal myotomy and partial fundoplication . Mean operative time was 180.5 minutes (range 145-264 minutes) . Mean length of stay was 1.98 days (range 1-18 days) . There were five (10%) perioperative complications but no esophageal leaks . There was a significant difference (P < 0.05) between the preoperative and postoperative dysphagia, chest pain, and regurgitation symptom scores . All patients stated that they were improved postoperatively . Eighty-six per cent rated their outcome as excellent, 10 per cent as good, and 4 per cent as fair . Laparoscopic anterior esophageal myotomy and Toupet fundoplication effectively alleviates dysphagia, regurgitation, and chest pain accompanying achalasia and is associated with high patient satisfaction, a rapid hospital discharge, and few complications. Rev Neurol, 2001 Sep 1-15, 33(5), 408 - 10 {Efficacy and tolerance of gabapentin in dystonia and hemifacial spasm: a pilot study}; Linazasoro Cristobal G; INTRODUCTION: The pharmacological management of dystonia is suboptimal . Focal dystonia and hemifacial spasm can be successfully managed with botulinum toxin injections . The physiopathology of dystonia remains a mystery . The gabaergic transmission may be involved in the origin of dystonia . Gabapentin is a gabaergic agent and therefore it can be useful in dystonia . PATIENTS AND METHODS: 28 patients with different forms of dystonia and hemifacial spasm were included in this open study . They received gabapentin (mean dose 1885 mg/d) . RESULTS: Gabapentin was not efficacious but a subgroup of 6 patients (3 with hemifacial spasm, 2 with posttraumatic dystonia and 1 with spasmodic torticollis) significantly improved . Gabapentin was well tolerated . Somnolence was the most commonly reported side effect . CONCLUSION: Gabapentin may be useful in some patients with dystonia and hemifacial spasm . Double blind studies are clearly needed. Dtsch Med Wochenschr, 2001 Nov 30, 126(48), 1361 - 4 {Early pain reduction in the treatment of spasticity after a single injection of botulinum A toxin}; Chalkiadaki A et al.; HISTORY, ADMISSION FINDINGS AND DIAGNOSIS: After stem-cell transplantation a 45-year-old woman (case 1) had an attack of general hypoxia requiring resuscitation . She then developed a quadriplegia and spasticity of all limbs notably of the right arm and a severe pain syndrome which had to be treated by oral and intravenous analgesics . Immobilisation and secondary complications aggravated the already difficult situation . In the 2nd case a 66-year-old woman was admitted to our outpatient clinic with long-standing left-sided spastic hemiparesis after territorial infarction of the right middle cerebral artery . Beside the spasticity she also suffered from a distinct pain syndrome which did not respond to any oral analgesics . TREATMENT AND COURSE: For the treatment of the main symptoms, both patients received intramuscular injections of 1000 MU botulinum toxin A (Dysport(R) Ipsen Pharma) . Astonishingly, both patients experienced pain relief the next day, whereas spasticity started to respond only 5-6 days later . CONCLUSIONS: In our experience pain relief after botulinum toxin A injections occurs not only due to reduced muscle hyperactivity, especially when such a temporal dissociation between pain relief and muscle relaxation appears as in the two cases reported above . Rather, we believe that botulinum toxin A interferes with the release of other neurotransmitters e . g . substance P (SP) and calcitonine-gene-related-peptide (CGRP) having a key function in the nociceptive cascade.
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