Botulinum Toxin Injections

Neurologic Uses

Botulinum toxin (BTx) is an important therapeutic agent with widespread applications in neurological and non-neurological disease. One of the most potent neurotoxins known, BTx derives from the Latin word “botulus” for sausage referring to poisoning from badly prepared meat in the early nineteenth century. BTx is a protein produced by Clostridium botulinum and is comprised of a heavy and light chain linked by a disulfide bond. When activated, it targets peripheral cholinergic systems and prevents the release of acetylcholine. The heavy chain mediates binding to presynaptic cholinergic nerve terminals and internalization of the toxin into the cell. The light chain is a zinc-endopeptidase responsible for its toxic effects and cleaves specific proteins needed for synaptic transmission.

Pullman-EMG-needle-300x225Purified and highly diluted, the first therapeutic use of BTx was as a treatment for strabismus in the 1970’s. BTx has seven serotypes, each with a specific mode of action at the molecular level. Currently, serotypes A (onabotulinumtoxinA or Botox, Allergan, Inc; abobotulinumtoxinA or Dysport, Ipsen, Ltd; incobotulinumtoxinA or Xeomin (NT-201), Merz Pharmaceuticals) and B (rimabotulinumtoxinB or Myobloc, US WorldMeds and Solstice Neurosciences, Inc) are available for clinical use. Over the last 25 years, BTx has proved t be remarkably successful in relieving spasms, unwanted movements, abnormal postures and associated pain in many disorders. The Clinical Motor Physiology Laboratory has been injecting among the largest number of patients in the world since the mid-1980’s. We specialize in musician’s dystonia and in complicated limb, trunk, head and neck injections using EMG guidance.
BTx injections have made it possible to control some neurologic conditions that used to require systemic therapy, and to avoid long-term consequences of muscle spasms and involuntary movements. Clinical trials have shown that BTx safely and effectively resolves excessive muscle contraction in dystonia (a condition characterized by sustained twisting and posturing movements which are usually
directional in nature), hemifacial spasm and other hyperkinetic disorders, spasticity from stroke, cerebral palsy, brain trauma, or multiple sclerosis, and excessive sweating in autonomic disorders.

Mónica-BTx1a-300x264BTx is a good therapeutic option that lasts for several months, is temporary and self-limited, and has few side effects. Side effects mainly consist of unwanted weakness in the injected muscles or spread into adjacent muscles. This is particularly troublesome in eyelid injections where droopiness may occur, and bilateral neck injections where trouble swallowing may occur. Excess weakness can be avoided by using low BTx doses and EMG-guided injections. EMG guidance into selected muscles is helpful for accurate muscle localization, particularly for limb conditions such as writer’s cramp. Systemic side effects, such as a transient flu-like syndrome, are very rare. Long term studies have shown that BTx continues to be effective and is safe after repeated use over many years.

The following are the main neurologic conditions that we treat with BTx injections:

Dystonia

Dystonia represents a group of clinical disorders characterized by various combinations of involuntary muscle contractions, abnormal postures and movements, usually in one direction, tremors and pain. Dystonia can occur at rest but is more likely to appear during voluntary activity. The early clinical descriptions of writer’s cramp from the late 19th century characterizing the altered voluntary activity, stiffness and pain remain accurate today.
The diagnosis of dystonia is made clinically by observing sustained muscle contractions, twisting oscillatory movements or abnormal postures. Nerve conduction studies, short and long loop reflexes and analysis of motor units are normal. Ballistic movements, normally tri-phasic in pattern with alternating agonist-antagonist bursts, may show disrupted patterns with co-contraction of agonist and antagonist muscles and excessively long EMG bursts in dystonia. However, not all patients have involvement of the same muscles during dystonic movements nor do they demonstrate the same abnormal firing patterns. The only clinical abnormalities on examination in primary dystonia or occupational cramps are the dystonic movements and postures themselves. No weakness, muscle atrophy, sensory loss, reflex asymmetry or other localizing or lateralizing signs should be found. The presence of such abnormalities suggests a secondary cause for the dystonic symptoms or a different clinical syndrome.

Music-2-Pullman-Fellow-300x225Focal limb dystonia affects one body area and typically presents as task-specific muscle spasms or “occupational cramps” in which learned or repetitive motor tasks (such as writing or playing a musical instrument) trigger muscle spasms. These interfere with specific tasks while other actions remain normal. This is also called focal task-specific dystonia (FTSD). Writer’s cramp is the most common form FTSD where involuntary muscle activity and abnormal postures affect the arms and hands. Patients with writer’s cramp typically experience involuntary dystonic spasms that result in altered writing speed and script quality. Dystonic spasms, loss of movement speed and decreased fluency when performing learned motor skills also occurs in musicians, dentists, golfers and numerous other occupations whose skilled work activity involves frequent, highly controlled, repetitive movements.

Segmental dystonia involves several adjacent muscle groups, and usually affects the hand or foot as well as more proximal regions such as the upper arm or shoulder. Segmental dystonia often begins more focally and then spreads to involve more muscles and actions. Generalized torsion dystonia always involves at least one leg and adjacent body regions, often includes the arms and is associated with the DYT1 gene. Currently, there are many new genetically classified dystonic syndromes under investigation. Generalized dystonia characteristically begins in childhood in one body region and progresses to affect both proximal and distal motor function.

Dystonic movements are intriguing in that they may be suppressed (or triggered) by sensory input such as postural change, tactile stimuli, alternative movements or even thought processes. FTSD is thought to be caused by an exaggeration of normal mechanisms of brain plasticity, that is, the processes by which the brain normally adapts. Repeated tasks, such as with the hand or fingers, result in reorganization of the brain and functional augmentation of those areas controlling the hand or fingers. FTSD also may be due, in part, to abnormal sensory processing or changes in spinal cord inhibition and regulation of muscle tone. This helps explain the nature of these sensory “tricks” as well as why the benefits of BTx typically outlast any weakness it causes in the injected muscles.

Spasticity

Spasticity is characterized by velocity-dependent increases in muscle tone and deep tendon reflexes, and is part of the upper motor neuron syndrome. Spasticity is common in neurological disease in adults and children. Typical causes include stroke, other central nervous system lesions, traumatic brain and spinal cord injury, hypoxic nervous system damage, multiple sclerosis and cerebral palsy.

Spasticity usually presents as impaired movement, weakness, painful muscle spasms and stiffness. Other problems include difficulty dressing, excoriation of the palm due to finger hyperflexion, problems with hygiene, disabling limb and trunk postures and decreased joint range of motion. Severe or long-standing spasticity may lead to contractures and joint ankylosis. BTx has been found to be beneficial to some degree in most forms of spasticity, though relatively higher doses often are needed compared to other limb conditions.

Diminishing increased tone and spasms in spastic limbs with BTx can “uncover” central weakness, in addition to causing peripheral weakness. In most cases, however, this does not occur perhaps in part to the effect of BTx on different types of muscle fibers. Reducing muscle over-activity in spasticity may even uncover residual power. More research is needed to investigate issues related to the best BTx doses, combinations of different formulations of BTx and prevention of antibody formation in patients with spasticity where high doses are needed.

Tremor

Tremors are among the most common of all movement disorders and are characterized by rhythmic oscillations of part of the body around one or more joints. The many kinds of tremor with numerous underlying causes generally fall into one or a combination of four broad characteristics: 1) whether they occur at rest, 2) while maintaining a posture, 3) with generalized activity, or 4) during the execution of a specific task. BTx injections are less effective in tremor disorders compared to dystonia or spasticity though can be of benefit in selected patients and can be tried at least once without harm.

Pain

Muscle spasms from any cause can be associated with a significant amount of pain, the alleviation of which was one of the major goals with BTx therapy. BTx is highly successful in relieving painful spasms in many patients who present with pain. Several mechanisms likely mediate musculo-skeletal pain including the extremes of posture, excessive tendon and joint tension and direct muscle fiber injury. BTx therapy has been shown to be useful in alleviating pain in many of the focal dystonias, particularly in torticollis.

Does BTx act through additional, as yet unknown pain relieving mechanisms? Animal investigations found that BTx may alter pain physiology through modulation of substance P, glutamate and calcitonin gene-related peptide. These substances are present at nerve endings and are thought to play important roles in pain sensation. Anecdotal reports about the possible analgesic effect of BTx on conditions where pain is the predominant issue, such as migraine headache and non-neurologic musculoskeletal conditions are still being investigated.

EMG guidance

Expertise and training in EMG is most important when treating conditions that affect the arms and legs. For limb applications of BTx, distinction should be made between using EMG for clinical diagnosis, for physiological investigation, for determining which muscles need to be treated and for actually performing BTx injections. EMG is useful for the first three points and almost always necessary for the last. This is because the involved muscles in limb conditions are more numerous, often not superficial and cannot always be palpated.