Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective was to evaluate whether removal of neutralising antibodies potentially resensitises a secondary non-responder to botulinum neurotoxin A (BoNT/A). Neutralising antibodies directed against BoNT/A are produced during long term treatment with BoNT/A-hemagglutinin complex in up to 10% of patients with cervical dystonia. These patients become secondary non-responders. Other serotypes of BoNT are not yet generally available and may also bear the risk of inducing antibody formation. Plasma exchange (PE) (one treatment cycle) and immunoadsorption on a protein A column (IA-PA; three treatment cycles) was employed over 15 months to remove neutralising antibodies from a severely disabled secondary non-responder with cervical dystonia. After plasma exchange or IA-PA, BoNT/A was reinjected. Antibodies were measured with a sensitive functional toxin neutralising test. Repeated use of plasma exchange and IA-PA depleted neutralising antibodies to below the detection limit and subsequently allowed successful BoNT/A injection into dystonic muscles. No serious side effects were found related to the depletion of IgG. In conclusion PE or IA-PA performed before BoNT/A readministration may provide an alternative strategy in treating selected secondary non-responders who are severely disabled.
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PMID:Depletion of neutralising antibodies resensitises a secondary non-responder to botulinum A neurotoxin. 985 74

Data from 616 patients suffering from idiopathic cervical dystonia were analyzed to determine the efficacy and safety of treatment with botulinum neurotoxin type A (BoNT/A). Since the specific purpose of this study was to determine the long-term effects of this treatment, the analysis focused specifically on the patients (n = 303) having received six or more injections. Statistical analysis of a standardized documentation showed sustained significant benefit as measured by a disease severity score independent of the type of cervical dystonia. Furthermore, pronounced individual differences were found in response to this treatment although initial clinical scores and doses of BoNT/A were similar. There was no indication of previously unknown adverse events, the only risk being the development of serum antibodies against the toxin. As in previous studies on short-term effects of BoNT/A treatment, the most frequent adverse event was dysphagia, which occurred on average 9.7 days after injection and lasted on average 3.5 weeks. While secondary nonresponse was seen in approx. 5% of patients, antibody tests revealed neutralizing serum antibodies in only 2%. On the basis of the present data, therapy of cervical dystonia with BoNT/A seems to be safe and yields good stable results even after 5 years of treatment.
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PMID:Long-term treatment of cervical dystonia with botulinum toxin A: efficacy, safety, and antibody frequency. German Dystonia Study Group. 1036 94

Botulinum toxin type B (BTX-B) is a member of a family of neurotoxins produced by the anaerobic bacteria Clostridium botulinum. BTXs specifically inhibit acetylcholine release at the neuromuscular junction and cause muscle paralysis in humans. The mechanism of action of BTXs involves inactivation of the neural exocytotic pathway by proteolytic cleavage of components of the exocytotic apparatus. Purified BTXs have been used clinically to treat disorders of muscle contraction, such as spasticity and dystonia. BTXs are purified as high molecular weight complexes that contain additional bacterial proteins which function to protect the toxin molecule. BTX complexes are stable in solution only at acidic pH. A new method was developed to purify intact BTX-B complexes. The resulting liquid formulation of high specific activity BTX-B (Elan's BTX-B evaluated as NeuroBloc) is buffered at pH 5.6 and demonstrates long-term stability at 2 to 25 degrees C.
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PMID:The biochemistry of botulinum toxin type B. 1118 81

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.
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PMID:Update on the botulinum neurotoxins. 1181 96

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.
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PMID:[Initial experiences with clinical use of botulinum toxin type B]. 1197 99

Although treatment with botulinum toxin type A (BTXA) has become the standard of care for most patients with laryngeal dystonia, its use is limited by the development of resistance to the toxin in some patients. Botulinum toxin type B (BTXB) has been found to be safe and effective in the treatment of cervical dystonia, but it has not been used previously to treat spasmodic dysphonia. Our experience with BTXB in a patient who developed resistance to BTXA suggests that BTXB may be safe and effective for the treatment of laryngeal dystonia, as well.
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PMID:Botulinum toxin type B for treatment of spasmodic dysphonia: a case report. 1239 95

Neutralization of antibodies poses a problem for a substantial number of cervical dystonia (CD) patients treated with botulinum toxin type A (BoNT/A). Presence of these antibodies may lead to a secondary nonresponse to BoNT/A treatment. In this study, we compared 6 antibody-positive (Ab+) with 12 antibody- negative (Ab-) CD patients treated with BoNT/A (Dysport) and matched for du- ration of treatment, number of BoNT/A injections, and severity of clinical symptoms. The two groups differed in cumulative BoNT/A dose (Ab+, 5984 mouse units [MU ], SD = 3151 MU; Ab-, 3143 MU, SD =1294 MU; P <.05), in addition, ab+ patients were significantly younger (ab+ mean age = 41.3 y, sd =5.9 y; ab - mean age = 56.8 y, sd = 15.3 y; p <.05), in or- der to avoid formation of neutralizing antibodies, doses of bont/a should be kept as low as possible, the risk of antibody formation seems to be higher in younger patients.
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PMID:Neutralizing botulinum toxin type a antibodies: clinical observations in patients with cervical dystonia. 1239 62

For the treatment of focal spasticity using botulinum toxin, only studies using type A have been published. Botulinum toxin type B (Neurobloc) is registered for cervical dystonia, but there is increasing interest in ist effectiveness for treating other diseases. Four patients, each with seriously disabling hip adductor spasticity of different origins, were treated with botulinum toxin type B following the failure of other therapeutic options. Total doses of 10,000 IU to 22,000 IU were injected bilaterally into the hip adductor muscles. A reduction in muscle tone or painful spasms was observed in all patients within 2 weeks, leading to an improvement in gait and increased ease of nursing care. Therefore, botulinum toxin type B may be a more cost-effective treatment for hip adductor spasticity than botulinum toxin type A.
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PMID:[Treatment of hip adductor spasticity with botulinum toxin type B]. 1248 68

Botulinum toxin has dramatically improved the treatment of a variety of neurologic disorders. Two botulinum toxin preparations are commercially available in the United States: type A (Botox) and type B (Myobloc). Current indications approved by the United States Food and Drug Administration include cervical dystonia, strabismus, blepharospasm, hemifacial spasm, and glabellar wrinkles for Botox, and cervical dystonia for Myobloc. Botulinum toxin inhibits release of acetylcholine from the neuromuscular junction, resulting in a localized paralysis when minute doses are injected. This mechanism enables botulinum toxin to alleviate symptoms of focal dystonias (which are characterized by excessive muscle contraction), and it may also, along with other theoretical mechanisms, be responsible for pain relief. Studies conducted in patients with cervical dystonia have shown that botulinum toxin effectively reduces pain associated with this disorder, suggesting that this agent may be effective in alleviating other painful syndromes.
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PMID:Review of the FDA-approved uses of botulinum toxins, including data suggesting efficacy in pain reduction. 1256 61

This article reviews the current status of dermatological uses for botulinum toxin type A (Botox), recently approved in the United States for treatment of glabellar wrinkles, and type B (Myobloc), approved for cervical dystonia. The respective formulations of Botox and Myobloc are described, and injection techniques and special considerations for administration in the treatment of dermatologic conditions are also discussed. The use of botulinum toxin injections for cosmetic treatment of movement-related facial lines and platysmal bands in the neck is reviewed, including injection procedures, efficacy, and potential complications. Recent developments in the use of botulinum toxins for the treatment of palmar and axillary hyperhidrosis are also described, comparing type A and type B results. Although direct comparisons between botulinum toxins for dermatologic applications are complicated by the lack of functional equivalence of the standard potency assays, appropriate dosing strategies for obtaining satisfactory clinical results using type B are being established, which will add to the experience already gained with type A. The diffusion characteristics of type B appear to show different and potentially advantageous clinical profiles in the treatment of crows' feet and hyperhidrosis compared with type A.
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PMID:Review of the use of botulinum toxin for hyperhidrosis and cosmetic purposes. 1256 68


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