Physiological effects of botulinum toxin in spasticity.
There is considerable evidence that injection of botulinum toxin (BTX) into muscles with spastic overactivity reduces resistance to passive movement in joints supplied by the injected muscles. The demonstration of improvement in active performance of the paretic limbs has been only anecdotal to date, and represents the most difficult challenge in research on BTX therapy in spastic paralysis. Data are reviewed that indicate several neurophysiological actions of BTX, other than the blocking of acetylcholine release at the neuromuscular ending: effects on the central nervous system, including retrograde axonal transport, reduced motoneuronal excitability, action on central synapses such as decreased Renshaw inhibition and increased presynaptic inhibition; action on gamma motoneuronal endings; action on most active terminals; spread of BTX to neighboring muscles; spread of BTX effects to remote muscles. Several of these neurophysiological actions are likely to contribute to improvement in active movements, as they may antagonize the primary mechanisms of functional impairment in patients with spastic paralysis: weakness, spastic cocontraction, spastic dystonia, and muscle shortening. We review the evidence for reduction of spastic cocontraction in both the injected muscle and its antagonist, and for improvement of antagonist weakness after BTX injection. The capacity of intramuscular BTX to reduce spastic dystonia and lengthen shortened muscles is also discussed based on prior literature. When injected into the more overactive of a pair of spastic antagonists around a joint, BTX should affect all the main mechanisms impairing active function around the joint.
Gracies
Jean-Michel
JM
Department of Neurology, The Mount Sinai Medical Center, New York, New York 10029-6574, USA. jean-michel.gracies@mssn.edu
D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001369:Axons / Q000187:drug effects; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects*; D004550:Elbow / Q000502:physiology; D004576:Electromyography; D006801:Humans; D007273:Injections, Intramuscular; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000503:physiopathology; D009132:Muscles / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
D018726:Anti-Dyskinesia Agents; D001905:Botulinum Toxins