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Botulinum Toxin and Its Uses
by Shabbir A. Abbasi, M.D., MRCP (UK)
Division of Neurology/Movement Disorders
The most potent biological toxin, Botulinum, has become a powerful therapeutic tool in the treatment of a variety of neurological, ophthalmologic and other disorders that are manifested by abnormal, excessive, or inappropriate muscle contractions. Work with botulinum toxin type A (Botox) as a therapeutic agent to treat human disease began in the late 1960s. The commercial use of the toxin begin in 1989.
Mode of Action
The therapeutic value of botulinum toxin is due to its ability to cause chemodenervation. The toxin acts by interfering with the presynaptic release of acetylcholine, producing local paralysis when injected into a muscle. Seven types of the toxin exist, but only type A is used clinically. The use of other toxins is being evaluated in clinical trials at present. The clinical applications of the botulinum toxin provide benefit to a wide variety of patients.
Blepharospasm
Patients with blepharospasm have intermittent or sustained bilateral eyelid closure as a result of involuntary contractions of the orbicularis oculi muscles. Associated spasm of the frontalis muscles may also be present. The effectiveness of botulinum toxin in treating blepharospasm has been shown in several double blind placebo controlled trials. The average duration of benefit may last up to 15 weeks, after which re-injection may be needed. Side effects may include transient ptosis (drooping of the eyelid), blurring of vision, diplopia (double vision), tearing, and hematoma. Treatment with the toxin has reversed functional blindness in patients who have been severely disabled due to this condition.
Hemifacial Spasm
Hemifacial spasm is defined as a neurological disorder manifested by involuntary recurrent twitches of the eyelids, perinasal and other facial muscles. The condition is not only annoying for the patient but also socially embarrassing, and in some patients produces severe disability. Local injection of hemifacial spasm muscles with botulinum toxin helps to suppress the symptoms for several months and provides a safe alternative to microvascular decompression of the facial nerve.
Tremor
Tremor is the most movement disorder. Tremor is an oscillatory movement produced by alternating or synchronous contractions of antagonistic muscles. Botulinum toxin treatment has been shown to effectively reduce the amplitude of tremor in patients in whom tremor produces a greater degree of disability and who are not satisfactorily controlled by pharmacotherapy.
Spasticity and Rigidity
Hypertonic disorders which result from cerebral palsy or as sequelae to cerebrovascular accidents may result in disabling spasticity. Local injection of botulinum toxin may, by relieving spasticity, provide functional improvement. This may result in improved walking, improved posture of wheelchair patients, hygienic betterment with improvement of muscle spasms, easier extension of arms and knees, and overall an improved quality of life. The toxin may also alleviate pain and may be used in therapeutic trials for prediction of the response to surgical elongation.
Intractable Migraine and Chronic Headache
Patients with intractable migraine or other types of headache who are non-responders to pharmacotherapy may have a good response to botulinum toxin injection in the frontalis and temporalis muscles. Pericranial injection of botulinum toxin type A has been found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.
Dystonias
Dystonia is characterized by involuntary muscular contraction, causing twisting movements and abnormal postures. The use of botulinum toxin has drastically changed the quality of life of patients suffering from focal dystonia and has proved useful in reducing the severity of some symptoms in the generalized form. Some of the focal forms of dystonia which respond to botulinum toxin includes oro-mandibular and laryngeal dystonia.
Cervical Dystonia or Spasmodic Torticollis
Dystonia of the neck muscles results in abnormal head and neck posture, commonly referred to as Spasmodic Torticollis. The goal of therapy of cervical dystonia is not only to improve abnormal posture of the head and associated neck pain, but also to prevent secondary complications such as contractures, cervical radiculopathy, and cervical myelopathy. The average duration of benefit may last up to 3-4 months, after which it may be necessary to repeat the injection. Transient and uncommon side effects include neck weakness, dysphagia, and nausea. The injection is usually done under EMG control so as to select the muscles which are most active electrophysiologically.
Writer's Cramp and Other Limb Dystonia
A common type of limb dystonia—writer's cramp—is task specific and the symptoms appear as soon as the pen is picked up or after writing a few words. Similarly other limbs muscles may present with inappropriate contractions. The injection of botulinum toxin in the inappropriately contracting muscles helps to relieve the symptoms somewhat and improve function. Other modalities of treatment have proved disappointing.
Motor Tics
A tic is an involuntary rapid nonrhythmic movement or sound. Some patients have troublesome tics that may cause functional blindness, local discomfort and social embarrassment. The response to botulinum toxin injection may bring about a drastic reduction in the severity of the symptoms.
Other Uses
Other uses of the botulinum toxin may includes injection to flatten hyperfacial lines and wrinkles; to reduce excessive sweating; in certain cases to relieve intractable back pain which may be due to excessive muscles spasm; to reduce stiff person syndrome; and to overcome spasm in the anogenital region and bruxisim in some cases.
Summary
In summary, Botulinum toxin has become an extremely useful tool in treating a wide variety of clinical conditions. The benefit provided has improved patient quality of life at a cost of relatively minimal and transient side effects.
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