Botulinum toxin adverse effects

MS patients usually have upper motor neuron spasticity. This type of spasticity cannot be treated with muscle relaxants such as carisoprodol. MS patients must be treated with agents specific for upper motor neuron spasticity (Table 26—8).48 MS spasticity is classified as focal or generalized. If the spasticity primarily involves only one muscle group, it is focal and may benefit from botulinum toxin administration.11 Systemic medications are used for generalized spasticity. No clear conclusion can be reached regarding the superiority in efficacy of one antispasticity agent over another medication selection is usually based on adverse effects (see Table 26-8).11,48... 

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. 

Consequently, botulinum toxin represents a strategy for dealing with spasticity that is especially problematic in specific muscles or groups of muscles. Despite the rather ominous prospect of injecting a potentially lethal toxin into skeletal muscles, this intervention has a remarkably small incidence of severe adverse effects when administered at therapeutic doses.5,44 Botulinum toxin can therefore be used as part of a comprehensive rehabilitation program to provide optimal benefits in certain patients with severe spasticity. 

Clozapine has been used to treat benign essential tremor refractory to the usual drugs (propranolol, primidone, alprazolam, phenobarbital, and botulinum toxin) in a randomized, double-blind, crossover study in 15 patients with essential tremor (58). Responders with more than 50% improvement after a single dose of clozapine 12.5 mg, compared with placebo, subsequently received 39-50 mg unblinded for a mean of 16 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients sedation was the only adverse effect reported. 

Recently, the extreme potency of botulinum toxin has led to multiple medical uses of this substance, including the treatment of cervical torticollis, strabismus, and other musculoskeletal disorders, as well as in cosmetic plastic surgery as Botox for the elimination of facial lines or wrinkles (Lemonick, 2002). The irreversible action of botulinum toxin on nerve transmission when used in minute amounts leads to prolonged therapeutic effects of greater than 3 months in duration. An iatrogenic form is also reported secondary to adverse effects of local injection of the toxin in cosmetic procedures or in patients with spasticity (Ihgnoli, 2002). 

A multicenter, double-blind, randomized, placebo-controlled study in 320 patients with untreated hyperhidrosis showed a more than 50% reduction in sweat production at 4 and 16 weeks after treatment respectively in 94 and 82% of patients treated with botulinum toxin (50 MU per axilla) and in 36 and 21% of placebo-treated patients (7). The major treatment-related adverse effect was an increase in sweating in non-axillary sites after treatment. Open treatment with botulinum toxin A was offered to patients in whom sweat production was at least 50% of baseline values (8). Of 207 study subjects, 39% had one treatment, 45% had two treatments and 15% had three treatments. Response rates 4 weeks after treatment were 96, 91, and 83% after the first, second, and third treatments respectively. In one of 207 patients there was possible transient seroconversion from negative to positive for neutralizing antibodies to botulinum toxin, and subsequent treatment with botulinum toxin resulted in complete disappearance of axillary sweating 7 days after injection. 

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. 

Comparative studies In a randomized blinded comparison of botulinum toxin with isosorbide dinitrate in the treatment of chronic anal fissure, adverse effects were similar in the two groups [51. ... 

Comparative studies Oral baclofen has been compared retrospectively with tizanidine as adjuvant therapy to botulinum toxin type A in the management of spasticity in children [77 ]. In 30 children with gastrocnemius spasticity, of whom 17 were treated with adjuvant oral baclofen and 13 received tizanidine, the mean Gross Motor Functional Measurement scores (77 versus 68) and caregiver questionnaire scores (70 versus 67) were higher with tizanidine than baclofen. The authors suggested that the combination of botulinum toxin type A with tizanidine is more effective and causes fewer adverse reactions than the combination of botulinum toxin type A and oral... 

In a retrospective study of single and multilevel injections of phenol, botulinum toxin, or both in children with chronic muscle spasticity, the local adverse effects were comparable with other previously reported studies. However, in contrast to previous studies, rare cases of dysesthesia (0.4%) were reported with phenol injections [72 j. 

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