Botulinum toxins treatment

Naumann M, Jost W (2004) Botulinum toxin treatment of secretory disorders. Mov Disord 19 Suppl 8 S 137 11... 

Holmes JM, Beck RW, Kip KE, et al. Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis. JAAPOS 2000 4 145-149. 

Generalized weakness has been reported after botulinum toxin treatment in a patient with amyotrophic lateral sclerosis (18). 

Stell R, Coleman R, Thompson P, Marsden CD. Botulinum toxin treatment of spasmodic torticollis. BMJ 1988 297(6648) 616. 

Simpson LL. The effects of acute and chronic botulinum toxin treatment on receptor number, receptor distribution and tissue sensitivity in rat diaphragm. J Pharmacol Exp Ther 1977 200(2) 343-51. 

It is not understood clearly, however, why sprouting occurs predominantly from nerve terminals following botulinum toxin treatment, whereas sprouting occurs from both nodes of Ranvier and terminals in nerve regeneration. An IGF dose effect on axons might be responsible, because IGF-I and IGF-II mRNAs are increased in nerve and IGF-II mRNA in muscle, during nerve regeneration. By contrast, one would not expect botulinum toxin to increase IGF mRNA content in nerves. 

There are reports of the benefits of botulinum toxin in the treatment of cerebral palsy in children. The toxin, produced by Clostridium botulinum, is a powerful and deadly poison, but is also an effective muscle relaxant. It is not licensed for use as such in the UK but is undergoing clinical trials. Current evidence suggests that repeat injections are necessary some 4-6 months after the first. 

Treatment—Since C. botulinum toxin blocks the actions of nerves that activate muscles necessary for breathing, an antitoxin can be injected up to about 24 hours (based on monkey studies) after exposure to a lethal toxin dose and still prevent death. The two types of available antitoxins prepared from horse sera are trivalent (includes types A, B, E) and heptavalent (types A, B, C, D, E, F, and G) preparations. It should be noted that patients face a theoretical risk of developing serum sickness from such antitoxins. 

The binary Clostridium botulinum toxin C2 blocks the function of actin filaments similarly to cytochalasin D (92). Treatment is for one to four hours in concentrations of 50ng/100ng or 100ng/200ng prior to adding liposomes. 

Reconstitute with 0.9% sterile, nonpreserved saline (100 units in 2.5 mL saline) prior to IM injection. The resulting formulation will be 4 units/0.1 mL and a total treatment dose of 20 units in 0.5 mL. The duration of activity of botulinum toxin type A for glabellar lines is approximately 3 to 4 months. Injection intervals should be no more frequent than every 3 months and should be performed using the lowest effective dose. The safety and efficacy of more frequent dosing have not been clinically evaluated more frequent dosing is not recommended. 

Strabismus (Botox only) The volume of botulinum toxin type A injected for treatment of strabismus should be between 0.05 to 0.15 mL per muscle. 

Safe and effective use Safe and effective use of botulinum toxin type A depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering botulinum toxin type A must understand the relevant neuromuscular or orbital anatomy of the area involved and any alterations to the anatomy caused by prior surgical procedures. An understanding of standard electromyographic techniques is also required for treatment of strabismus and may be useful for the treatment of CD. 

Retrobulbar hemorrhages During the administration of botulinum toxin type A for the treatment of strabismus, retrobulbar hemorrhages sufficient to compromise retinal circulation have occurred from needle penetrations into the orbit. It is recommended that appropriate instruments to decompress the orbit be accessible. Ocular (globe) penetrations by needles have also occurred. An ophthalmoscope to diagnose this condition should be available. Inducing paralysis in 1 or more extraocular P.788... 

Injection site Use caution when botulinum toxin type A treatment is used in the presence of inflammation at the proposed injection site(s) or when excessive weakness or atrophy is present in the target muscle(s). 

Immunogenicity Treatment with botulinum toxin type A may result in the formation of antibodies that may reduce the effectiveness of subsequent treatments with botulinum toxin type A for glabellar lines or other indications. 

Primary axillary hyperhidrosis Adverse events (in at least 3% of patients) included injection site pain and hemorrhage, nonaxillary sweating, infection, pharyngitis, flu syndrome, headache, fever, neck or back pain, pruritus, and anxiety. Blepharospasm The most frequently reported treatment-related adverse reactions were ptosis (20.8%), superficial punctate keratitis (6.3%), and eye dryness (6.3%). Strabismus Extraocular muscles adjacent to the injection site can be affected, causing ptosis, vertical deviation, spatial disorientation, double vision, or past-pointing, especially with higher doses of botulinum toxin type A. 

Forced dilatation at endoscopy or surgical cardiomy-otomy are the treatments of choice, although injection of botulinum toxin (which needs repetition) is also effective. Temporary relief can, be obtained with sublingual or inhaled glyceryl trinitrate. 

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. 

C. Hydroquinone inhibits the enzyme tyrosine kinase, which converts tyrosine to melanin. It also damages melanocytes. Becaplermin (A) is a recombinant human platelet-derived growth factor that is useful in enhancing wound healing. Etanercept (B) is a recombinant fusion protein approved for treatment of psoriatic arthritis and rheumatoid arthritis. Botulinum toxin (D) is a purified form of bofu-linum foxin fype A approved for fherapy of blepharospasm and sfrabismus. 

A randomized, double-blind, placebo-controlled crossover trial of botulinum toxin for the treatment of simple motor tics was conducted in 20 patients, ages 15-55, 18 of whom completed the study (Marras et al., 2001) (Table 40.2). As rated blindly on a 12-minute videotape sample, the proportional change in treated tics per minute was —39% during the botulinum toxin phase in contrast to an increase of +5.8% during the placebo phase. Half of the patients noted weakness of the injected muscles that was not functionally disabling. Two patients reported inner restlessness, accompanied by an increased urge to perform the treated tic. Two others felt that the decrease in the treated tic prompted a new replacement tic. Despite improvement in the treated tic, there was no significant evidence of overall improvement. 

Jankovic, J. (1994) Botulinum toxin in the treatment of dystonic tics. Mov Disord 9 347—349. 

The therapeutic use of botulinum toxin for ophthalmic purposes and for local muscle spasm was mentioned in Chapter 6. Local facial injections of botulinum toxin are widely used for the short-term treatment (1-3 months per treatment) of wrinkles associated with aging around the eyes and mouth. Local injection of botulinum toxin has also become a useful treatment for generalized spastic disorders (eg, cerebral palsy). Most clinical studies to date have involved administration in one or two limbs, and the benefits appear to persist for weeks to several months after a single treatment. Most studies have used type A botulinum toxin, but type is also available. 

Ronan S, Gold JT Nonoperative management of spasticity in children. Childs Nerv Syst 2007 23 943 [PMID 17646995] Verrotti A et al Pharmacotherapy of spasticity in children with cerebral palsy. Pediatr Neurol 2006 34 1. [PMID 16376270] Ward AB Spasticity treatment with botulinum toxins. J Neural Transm 2008 115 607. [PMID 18389166]... 

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. 

Injection of botulinum toxin A at the site of problematic tics is sometimes helpful. Treatment of any associated attention deficit disorder (eg, with clonidine patch, guanfacine, pemoline, methylphenidate, or dextroamphetamine) or obsessive-compulsive disorder (selective serotonin reuptake inhibitors or clomipramine) may be required. Bilateral thalamic stimulation is sometimes worthwhile in otherwise intractable cases. 

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. 

More recently, there has been considerable interest in using botulinum toxin to reduce spasticity in specific muscles or muscle groups. This treatment has been used to treat spasticity resulting from various dis-... 

Bakheit AM, Fedorova NV, Skoromets AA, et al. The beneficial antispasticity effect of botulinum toxin type A is maintained after repeated treatment cycles. J Neurol Neurosurg Psychiatry. 2004 75 1558-1561. 

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. 

Sarioglu B, Serdaroglu G, Tutuncuoglu S, Ozer EA. The use of botulinum toxin type A treatment in children with spasticity. Pediatr Neurol. 2003 29 299-301. 

Sycha T, Kranz G, Auff E, Schnider R Botulinum toxin in the treatment of rare head and neck pain syndromes a systematic review of the literature. J Neurol. 2004 251(suppl 1) I19-I30. 

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