Spasticity - Botulinum Toxin Type A

Spasticity

Botulinum Toxin Type A

Overview
Among the unusual breakthroughs in the history of medicine is the evolving clinical use of Botulinum Toxin Type A (BTX-A) as a therapeutic tool. BTX-A injections have been used as a safe and effective treatment for a variety of disorders of abnormal muscle tone, including muscle overactivity or spasticity. BTX-A therapy was FDA approved in 1989 for strabismus, blepharospasm, and hemifacial spasm in patients 12 years and older. The use of BTX-A to treat spasticity is off-label. Controlled clinical trials of BTX-A injections for focal muscle spasticity have demonstrated prolonged yet reversible clinical effects, few side effects, and minimal immunity.

BTX-A affects the neuromuscular junction through binding, internalization, and inhibition of acetylcholine release. It must enter the nerve endings to exert its chemodenervating effect. Once inside the cholinergic nerve terminal cell, BTX-A inhibits the docking and fusion of acetylcholine vesicles at the pre-synaptic membrane. Duration of effect is usually 3 to 4 months, but can be longer or shorter. Gradually, muscle function returns by the regeneration or sprouting of blocked nerves forming new neuromuscular junctions. BTX-A is dose-dependent and reversible secondary to the regeneration process.

The results of clinical trials strongly support the efficacy and safety of BTX-A for the treatment of spasticity in patients with upper motor neuron (UMN) syndrome caused by cerebral palsy, multiple sclerosis, stroke, spinal cord injury, brain injury, or neurodegenerative disease. Major benefits of BTX-A therapy for spasticity include improved function, increased ease of care and comfort, prevention or treatment of musculoskeletal complications, and cosmesis.

The most challenging aspect of BTX-A therapy is patient selection. Each patient's treatment must be individualized. Chronicity, severity, distribution, locus of injury, co-morbidities, availability of care, and treatment goals are important decision-making factors in managing spasticity. The use of BTX-A must be part of a comprehensive treatment plan. Increased range of motion, reduction in spasm frequency, or reduced pain are primary goals leading to what most patients desire, improved function. Treatment begins with mutually agreed upon goals and expectations, a treatment plan that addresses all the clinical issues, and a working partnership between patients and qualified professionals. (See Treatment Decision-Making.)

Dosing Guidelines
BTX-A dosing is patient-specific, and dependent upon muscles involved, prior response, and functional goals. The injection of a moderate initial dose with subsequent adjustments is advised. Although contraindications and side effects are minimal, conditions requiring caution include patients who are hypersensitive to any ingredient in BTX-A, using aminoglycoside antibiotics, diagnosed with neuromuscular disease, pregnant or may become pregnant, or in lactation.

Traditional Pharmacological Treatments for Spasticity Part I: Local Treaments
Jean-Michel Gracies, MD, PhD; Elie Elovic, MD; John McGuire, MD; David Simpson, MD
Editors: Nathaniel H. Mayer, MD; David M. Simpson, MD
Spasticity: Etiology, Evaluation, Management and the Role of Botulinum Toxin 2002: p52-72.

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