Dystonia botulinum toxins

Off-period dystonia, sustained muscle contractions that occur more commonly in distal lower extremity (e.g., foot), occur often in the early morning hours. They may be treated with bedtime administration of sustained-release products, use of baclofen, or selective denervation with botulinum toxin. 

Botulinum toxin is used clinically in the treatment of blepharospasm, writer s cramp, spasticities of various origins, and rigidity due to extrapyramidal disorders. It is also used to treat gustatory sweating and cosmetically to decrease facial wrinkles. Botulinum toxin A Botox, Oculinum) injected intramuscularly produces functional denervation that lasts about 3 months. Clinical benefit is seen within 1 to 3 days. Adverse effects range from diplopia and irritation with blepharospasm to muscle weakness with dystonias. 

Botox (Toxin) Muscle relaxation activity, cervical dystonia Botulinum sp. 

The pharmacologic basis of these disorders is unknown, and there is no satisfactory medical treatment for them. A subset of patients respond well to levodopa medication (dopa-responsive dystonia), which is therefore worthy of trial. Occasional patients with dystonia may respond to diazepam, amantadine, antimuscarinic drugs (in high dosage), carbamazepine, baclofen, haloperidol, or phenothiazines. A trial of these pharmacologic approaches is worthwhile, though often not successful. Patients with focal dystonias such as blepharospasm or torticollis often benefit from injection of botulinum toxin into the overactive muscles. The role of deep brain stimulation for the treatment of these conditions is being explored. 

Botulinum toxin has been used for some time to control localized muscle dystonias, including conditions such as spasmodic torticollis, blepharospasm, laryngeal dystonia, strabismus, and several other types of focal dystonias.6 25,26,87 93 When used therapeutically, small amounts of this toxin are injected directly into the dystonic muscles, which begin to relax within a few days to 1 week. This technique appears to be fairly safe and effective in many patients, but relief may only be temporary. Symptoms often return within 3 months after each injection, necessitating additional treatments.40 Still, this technique represents a method for treating patients with severe, incapacitating conditions marked by focal dystonias and spasms. 

Most muscle relaxants are absorbed fairly easily from the gastrointestinal tract, and the oral route is the most frequent method of drug administration. In cases of severe spasms, certain drugs such as methocarbamol and orphenadrine can be injected intramuscularly or intravenously to permit a more rapid effect. Likewise, diazepam and dantrolene can be injected to treat spasticity if the situation warrants a faster onset. As discussed earlier, continuous intrathecal baclofen administration may be used in certain patients with severe spasticity, and local injection of botulinum toxin is a possible strategy for treating focal dystonias and spasticity. Metabolism of muscle relaxants is usually accomplished by hepatic microsomal enzymes and the metabolite or intact drug is excreted through the kidneys. 

Balash Y, Giladi N. Efficacy of pharmacological treatment of dystonia evidence-based review including meta-analysis of the effect of botulinum toxin and other cure options. Eur J Neurol. 2004 11 361-370. 

Costa J, Borges A, Espirito-Santo C, et al. Botulinum toxin type A versus botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev. 2005 CD004314. 

Dressier D, Bigalke H. Botulinum toxin type B de novo therapy of cervical dystonia. Frequency of antibody induced therapy failure. J Neurol. 2005 252 904-907. 

Botulinum toxin is the treatment of choice for focal dystonias such as torticollis and writer s cramp and for hemifacial spasm, and may complement the management of spasticity. 

Botulinum toxin induces weakness of striated muscles by inhibiting transmission of motor neurons at the neuromuscular junction. This has led to its use in conditions with muscular overactivity, such as dystonia. Transmission is also inhibited at y neurons in muscle spindles, which may alter reflex overactivity. 

Chen R, Karp BI, Hallett M (1998b) Botulinum toxin type F for treatment of dystonia long-term... 

Jahn R, Lang T, Siidhof TC (2003) Membrane fusion. Cell 112 519-33 Jankovic J (2006) Botulinum toxin therapy for cervical dystonia. Neurotox Res 9 145-8 Jankovic J, Schwartz K (1995) Response and immunoresistance to botulinum toxin injections. Neurology 45 1743-6... 

Lew MF, Adornato BT, Duane DD, Dykstra DD, Factor SA et al. (1997) Botulinum toxin type B a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology 49 701-7... 

Two cases of severe oromandibular dystonia refractory to other antidystonic therapies, including botulinum toxin, which improved with clozapine have been reported (96). 

Botulinum toxin-B Myobloc (Elan) Cervical dystonia... 

Botulinum toxin-A Botox cosmetic (Allergen) Strabismus blepharospasm glabellar lines cervical dystonia axillary hyperidrosis... 

Biological products were developed traditionally, before recombinant proteins, as extracts or derivatives of the actual protein from the human body or nature. This approach continues today and Table 15 lists 18 such products, mostly blood derivatives for therapeutic use. Albumin is obtained for cardiovascular volume conditions. A fish protein is harvested for osteoporosis. Igs extracted from blood are available for immunodeficiency conditions, viral infections (hepatitis-B and vaccinia), hemolytic anemia in newborns, and idiopathic thrombocytopenic purpurea. Antihemophilic products are still derived from blood. An antiglobulin is produced for kidney transplant rejection. A collagen product and two botulinum toxin products are used for various facial wrinkle problems and cervical dystonia. A bacterial antigen is formulated to enhance immunity to treat a cancer. 

Botulinum toxin is used in the treatment of excessive muscle contraction disorders (dystonias), such as strabismus, blepharospasm, focal dystonias, and spasticity. One of its uses is in the removal of facial wrinkles by paralysing mimic muscles. It can reduce sweat production by blocking cholinergic innervation of eccrine sweat glands. 

Ansved T, Odergren T, Borg K. Muscle fiber atrophy in leg muscles after botulinum toxin type A treatment of cervical dystonia. Neurology 1997 48(5) 1440-2. 

Bhatia KP, Munchau A, Thompson PD, Houser M, Chauhan VS, Hutchinson M, Shapira AH, Marsden CD. Generalised muscular weakness after botulinum toxin injections for dystonia a report of three cases. J Neurol Neurosurg Psychiatry 1999 67(l) 90-3. 

Botulinum toxin type A is approved for use in humans for the treatment of strabismus, blepharospasm associated with dystonia, head position and neck pain associated with cervical dystonia (a movement disorder characterized by involuntary muscle contractions), as well as for the temporary improvement in the appearance of moderate to severe glabellar lines in adult men and women 65 years or younger. Clinical trials have noted few adverse effects associated with use of botulinum toxin type A for these conditions. 

Management Dose reduction, or change to a different drug, or addition of an M blocker. Acute dystonias may respond to botulinum toxin. 

Various other focal dystonias can be treated successfully by injections of botulinum toxin in the appropriate muscles. These include writer s cramp, spasmodic laryngeal dystonia which involves the vocal cords and is manifested as a strangled voice and... 

Botulinum toxin type B interferes with neurotransmitter release by cleaving synaptic vesicle-associated membrane protein. It is indicated in reduction of severity of abnormal head position and neck pain in adult patients with cervical dystonia. 

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