Ivanhoe_Cardiology_book_temp 25/09/2009 10:39 Page 38
Brain Trauma Stroke
Botulinum Toxin Type A and Post-stroke Spasticity of the Upper Limbs
Cindy B Ivanhoe, MD, PA and Natasha K Eaddy-Rose, MD
1. Associate Professor, Physical Medicine and Rehabilitation, Baylor College of Medicine, and Medical Director, NeuroRehabilitation Specialists;
2. Physician, NeuroRehabilitation Specialists
Abstract
Background: Stroke is a significant contributor to morbidity and mortality in the US and other developed nations. Stroke and its side effects are
the primary cause of disability in the US and worldwide. Upper limb mobility factors are particularly detrimental to activities of daily living.
Successful treatments to improve post-stroke spasticity are required. Objective: To assess the relevant medical literature related to the use of
botulinum toxin type A and post-stroke spasticity of the upper limb. Methods: Literature review utilizing Medline with keywords of botulinum
toxin, stroke, spasticity, and upper extremity since 2003. Results: Thirteen criteria-based articles investigated botulinum toxin type and post-
stroke spasticity of the upper limbs. Discussion: Botulinum toxin type A is an effective agent in reducing post-stroke spasticity of the upper limbs.
Keywords
Upper motor neuron syndrome (UMNS), botox, spasticity, neurorehabilitation, botulinum toxin type A, stroke, upper extremity
Disclosure: Cindy B Ivanhoe, MD, PA, has received funding from Medtronic and Allergan. Natasha K Eaddy-Rose, MD, has no conflicts of interest to declare.
Received: August 11, 2009 Accepted: September 3, 2009
Correspondence: Cindy B Ivanhoe, MD, PA, NeuroRehabilitation Specialists, 2211 Norfolk, Suite 220 Houston, Texas 77098. E:
cbivanhoe@att.net
Stroke is the leading cause of disability in the US and is a major global portion of the heavy chain of the molecule binding to the receptor on the
health problem. It has been identified as one of the largest causes of lost motor nerve cell surface. It is then internalized by receptor-mediated
productivity in late adulthood. The multiple life-altering complications endocytosis. When inside the cell, the light chain is released into the
that result from stroke—such as paresis, mood disorders, aphasia, cytoplasm, where it cleaves SNAP-25. This prevents the soluble N-
cognitive deficits, dysarthria, dysphagia, and visual disturbances—may ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
be confounded by the development of spasticity. Upper-limb spasticity protein from facilitating the release of acetylcholine into the synaptic
can be particularly debilitating. cleft. As a result, muscle contraction does not occur or occurs to a lesser
degree. It is also believed that BTX-A works similarly in sensory neurons,
Spasticity is considered to be a positive sign of the upper motor neuron where it blocks the release of neuropeptide neurotransmitters and
syndrome (UMNS) and, as such, is associated with exaggerated tendon inhibits the sensitization of the pain nerve. The effects of BTX-A are
jerks and repetitive stretch reflex discharges, or ‘clonus.’ Spasticity is a reversible with re-inervation of the original nerve terminal occurring.
disorder of the sensorimotor system defined as an involuntary, velocity-
dependent resistance to stretch, caused by a hyperexcitable stretch The US Food and Drug Administration (FDA) has recently reviewed safety
reflex. Spasticity is often a key component of a person’s experience of information for all botulinum toxins, introducing a Risk Evaluation and
impaired mobility and activities of daily living, pain, skin breakdown, poor Mitigation (REMS) Program for all available botulinum toxins. One of the
hygiene, insomnia, social isolation, and poor quality of life (QoL). These goals of the REMS programs is to minimize the risks of medication errors
conditions also have a significant impact on care-giver burden. Treatment related to the lack of interchangeability between botulinum toxins. To this
options for post-stroke spasticity include oral spasmolytics (e.g. baclofen, end the FDA has assigned new and unique non-proprietary names
dantrolene, and diazepam) and may not be tolerated by patients due to (BOTOX
®
onabotulinumtoxinA, Dysport™ abobotulinumtoxinA, and
their non-selective nature and systemic side effects such as sedation, Myobloc
®
rimabotulinumtoxinB). The studies reviewed herein used BOTOX
dizziness, nausea, cognitive dysfunction, and general weakness. They may and Dysport.
also yield limited functional benefit. Tolerance may lead to upward
titration of the dose, increasing the likelihood of side effects. The use of Objectives
botulinum toxin type A (BTX-A) has become a common treatment for This article focuses on post-stroke upper-extremity spasticity. A descriptive
post-stroke spasticity due to its favorable side effect profile, efficacy, and examination of the relevant literature was performed with the objectives
focal benefits. BTX-A acts by blocking presynaptic release of acetylcholine of: examining the efficacy of BTX-A injection in post-stroke upper-extremity
at the neuromuscular junction. It does this by action of the C-terminal spasticity; investigating whether or not reduction of spasticity translates
38 © TOUCH BRIEFINGS 2009
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