BOTULINUM TOXIN THERAPY

Abstract

BACKGROUND- Muscle overactivity (e.g., spastic dystonia and pathologic antagonistic cocontraction), in addition to motor weakness and muscle shortening, is one of the three cardinal disabling features in patients with damage to central motor pathways. Muscle overactivity is usually not distributed equally throughout the body; instead, it predominates in certain muscles. As a result, imbalance often exists between hypoactive agonists and relatively hyperactive antagonists. Treatments targeting overactivity in specific muscles (local treatments) may therefore be preferable to generalized therapies. This article reviews the physiological action, pharmacology, risks, and indications of the most promising of these local treatments, botulinum toxin (BTX). REVIEW SUMMARY- BTX is a neurotropic protein that blocks acetylcholine release from all cholinergic terminals, including peripheral motor nerves, which results in flaccid paralysis when injected into muscle. Seven serotypes of BTX are produced by several species of Clostridium, and some have been purified for therapeutic purposes. The paralyzing action of BTX is temporary, and recovery of function occurs after terminal nerve sprouting and reformation of neuromuscular junctions. No muscle or nerve destruction occurs after BTX injection into muscle, as opposed to neurolytic agents (e.g., alcohol and phenol), and clinical tolerance is usually excellent. To target specific muscles, the stimulation technique seems more effective than passive EMG monitoring. Because BTX blocks all cholinergic synapses, it has also been used in autonomic disorders as an antimuscarinic agent. CONCLUSIONS- BTX is a well-tolerated, local pharmacologic treatment for muscle overactivity, and its range of licensed indications will likely increase, particularly among spastic conditions. However, pharmaco-economic considerations mandate that controlled comparative studies between BTX and other neurolytic agents are performed. The genetic synthesis of a biologically active BTX may render this treatment more cost-effective in the future. (THE NEUROLOGIST 6:98-115, 2000)