Conditions: Focal Dystonia
Keywords: Myloboc Botulinum Toxin Type B Focal Dystonia Musicians Muscle Relaxants Motor Impairments Motor Performance Tremor Abnormal Postures
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 16
Healthy volunteers: no

Brief summary:
This study uses a computerized method of musical instrument digital interface (MIDI) quantification of performance before and after treatment with botulinum toxin type B (Myobloc ®, Solstice Neurosciences). Myobloc is a purified and diluted form of botulinum toxin used medically to relax unwanted muscle spasms and movements. The aim of the study is to determine the feasibility of quantifying change in performance following treatment.

Detailed description:
Dystonia represents a group of clinical disorders characterized by various combinations of sustained involuntary muscle contractions, abnormal postures and movements, tremors and pain. Dystonia can occur at rest but is more likely to appear during voluntary activity.

Focal dystonia affects one body area and includes blepharospasm, oromandibular dystonia, spasmodic dysphonia, torticollis, and limb dystonia. Focal dystonia 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 and interfere with performance while other actions remain normal. Writer's cramp is the most common form of idiopathic limb dystonia \[1-3\] where involuntary muscle activity and abnormal postures affect the arms and hands, but virtually any part of the body may be affected, even the lips when playing a woodwind or brass instrument \[4\]. Patients may develop two focal dystonias but rarely does focal dystonia progress to more generalized forms.

As originally defined by Oppenheim \[5\], dystonia refers to the slow, sustained, writhing, contorting movements of dystonia musculorum deformans. Dystonic movements, however, are often rapid \[6\] and this can be a cause for misdiagnosis. Electromyography (EMG) may be helpful in corroborating dystonia, but is not essential for diagnostic purposes. Nerve conduction studies, short and long loop reflexes and analysis of motor units are normal \[7, 8\]. Ballistic movements, which are 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 \[3\].

Dystonic spasms 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 \[9\]. Studies are revealing that the involuntary muscle spasms may be due, at least in part, to abnormal sensory processing of spindle afferent information \[10-12\]. This may help explain the nature of these sensory "tricks" as well as why the effect of treatment using botulinum toxin usually outlasts the weakness it creates.

Though the pathophysiology of musicians' dystonia has yet to be determined fully, the motor learning associated with playing a musical instrument probably results in both functional and structural changes in the brain \[13\]. This plastic reorganization, including the rapid unmasking of existing neural circuitry and the establishment of new connections, is probably fundamental to the accomplishment of skillful playing, but also may result in focal, task-specific dystonia. When musicians get dystonia, their playing abilities can become severely compromised, to the point where they may not be able to perform professionally, and possibly not even teach. While botulinum toxin injections can be highly successful in allowing musicians to perform again, there are no objective methods to evaluate improvement.

Subtle dystonic abnormalities in motor control, therefore, particularly when they involve the arms, are difficult to ascertain with a high level of certainty. There are no truly objective measures of arm dystonia, and this is problematic because arm involvement can present so mildly as to go unnoticed by the examiner \[14\]. Furthermore, patients may not complain of mild finger or thumb cramping, arm twisting or shoulder elevation that could signify the presence of dystonia.

Clinical rating scales, even those that have been validated, do not detect subtle motor dysfunction or small changes after treatment \[15\] and certainly cannot determine improvement in musical performance. Metabolic imaging studies using positron emission tomography (PET) studies are emerging as helpful ancillary tests, but these are invasive and expensive. Furthermore, while PET studies have implicated that primary dystonia may be associated with relative hypermetabolism in the putamen \[16\], there have been conflicting reports \[17\]. Another major difficulty in the study of musician's dystonias has been lack of objective, quantifiable methods to assess degrees of dystonia severity or measure of treatment effects. Subjective and objective clinical rating scales with varying degrees of sophistication. Some subjective methods that have been used include subjective quantification usually using percentage improvement, also different various subjective rating scales using surveys.

This study tests a novel method devised for quantifying change in musical performance based on musical instrument digital interface (MIDI) data that will be able to directly rate or score changes in musical output. MIDI data include information on the note played, the time of onset, note duration, and note loudness. Note duration and loudness will be used in this study. It will be a quantitative, objective computerized evaluation that compares the patients' fine motor skills before and after treatment with Myobloc ®. It will be one of the first quantitative analyses of musical ability of its kind and could significantly impact the way musicians determine the efficacy of botulinum toxin treatment.

REFERENCES

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17. Karbe H, Holthoff VA, Rudolf J, Herholz K, Heiss WD. Positron emission tomography demonstrates frontal cortex and basal ganglia hypometabolism in dystonia. Neurology 1992; 42: 1540-1544.
18. Pullman SL. Limb dystonia: Use of botulinum toxin. In Jankovic, J, Hallett, M, ed. Therapeutic Use of Botulinum Toxin. New York: Marcel Dekker, 1994: 307-321.
19. Medical Research Council Aids to the Examination of the Peripheral Nervous System; Crown: London, 1976.
20. Pullman SL, Greene P, Fahn S, Pedersen SF. Approach to the treatment of limb disorders with botulinum toxin A. Experience with 187 patients. Arch Neurol 1996; 53: 617-24.
21. Cohen LG, Hallett M, Geller BD, Hochberg F. Treatment of focal dystonias of the hand with botulinum toxin injections. J Neurol Neurosurg Psychiatry 1989; 52: 355-363.
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Arms:
arm 1: Diluted botulinum toxin (500 Units/0.1 ml) is injected to the affected muscle(s) through a hollow core needle using electromyographic guidance. Dosage according to muscle(s) and symptom severity. Injection occurs at first visit only, after neurological evaluation.

Interventions: intervention 1: Botulinum toxin, type B
Intervention descriptions: intervention 1: Diluted botulinum toxin (500 Units/0.1 ml) is injected to the affected muscle(s) through a hollow core needle using electromyographic guidance. Dosage according to muscle(s) and symptom severity. Injection occurs at first visit only, after neurological evaluation.

Protocol document: