Botulinum toxin neuromuscular disorders

This chapter deals with botulinum toxin type A (BOTOX) in the treatment of strabismus, blepharospasm, and related disorders. Botulinum toxin type A (BOTOX) has been used to treat strabismus, blepharospasm, Meige s syndrome, and spasmodic torticollis. By preventing acetylcholine release at me neuromuscular junction, botulinum toxin A usually causes a temporary paralysis of the locally injected muscles. The variability in duration of paralysis may be related to me rate of developing antibodies to me toxin, upregulation of nicotinic cholinergic postsynaptic receptors, and aberrant regeneration of motor nerve fibers at me neuromuscular junction. Complications related to this toxin include double vision (diplopia) and lid droop (ptosis). 

In the presence of nenromnscnlar disorders, such as myasthenia gravis or Lambert-Eaton sjmdrome, botulinum toxin-induced inhibition of acetylcholine release can cause generalized weakness (17). Therefore, botulinum toxin should, if at aU, be used with extreme caution in patients with neuromuscular disease, who have a reduced margin of safety with regard to neuromuscular transmission. 

While the exact cause of muscle weakness was unclear, this case argues against the use of botulinum toxin in patients with myasthenic syndromes. When the margin of safety is reduced with regard to neuromuscular transmission, botulinum toxin can result in increased morbidity or even mortality. Generalized muscle weakness after botulinum toxin has also been reported in patients with other neuromuscular disorders (18). In addition, it should be remembered that both dysphagia and muscle weakness can occur after botulinum toxin injection, even in patients who do not suffer from generalized neuromuscular disorders (19). 

An effective Botulinum neurotoxin-based drug delivery vehicle can be used to directly deliver toxin inhibitors into the intoxicated nerve terminal cytosol. The concept may possibly be utilized for drug delivery for other neuronal and neuromuscular disorders. Besides a BoNT therapeutic approach, this report also provides new fundamental knowledge of endocytosis and exocytosis as well as of BoNT trafficking in neurons. 

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