Stroke is the leading cause of disability in the US and is a major global health problem. It has been identified as one of the largest causes of lost productivity in late adulthood. The multiple life-altering complications that result from stroke—such as paresis, mood disorders, aphasia, cognitive deficits, dysarthria, dysphagia, and visual disturbances—may be confounded by the development of spasticity. Upper-limb spasticity can be particularly debilitating.

Spasticity is considered to be a positive sign of the upper motor neuron syndrome (UMNS) and, as such, is associated with exaggerated tendon jerks and repetitive stretch reflex discharges, or ‘clonus.’ Spasticity is a disorder of the sensorimotor system defined as an involuntary, velocitydependent resistance to stretch, caused by a hyperexcitable stretch reflex. Spasticity is often a key component of a person’s experience of impaired mobility and activities of daily living, pain, skin breakdown, poor hygiene, insomnia, social isolation, and poor quality of life (QoL). These conditions also have a significant impact on care-giver burden. Treatment options for post-stroke spasticity include oral spasmolytics (e.g. baclofen, dantrolene, and diazepam) and may not be tolerated by patients due to their non-selective nature and systemic side effects such as sedation, dizziness, nausea, cognitive dysfunction, and general weakness. They may also yield limited functional benefit. Tolerance may lead to upward titration of the dose, increasing the likelihood of side effects. The use of botulinum toxin type A (BTX-A) has become a common treatment for post-stroke spasticity due to its favorable side effect profile, efficacy, and focal benefits. BTX-A acts by blocking presynaptic release of acetylcholine at the neuromuscular junction. It does this by action of the C-terminal portion of the heavy chain of the molecule binding to the receptor on the motor nerve cell surface. It is then internalized by receptor-mediated endocytosis. When inside the cell, the light chain is released into the cytoplasm, where it cleaves SNAP-25. This prevents the soluble Nethylmaleimide- sensitive factor attachment protein receptor (SNARE) protein from facilitating the release of acetylcholine into the synaptic 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, where it blocks the release of neuropeptide neurotransmitters and inhibits the sensitization of the pain nerve. The effects of BTX-A are reversible with re-inervation of the original nerve terminal occurring.

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