Quantifying Musical Performance After Treatment With Myobloc in Musician's Dystonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00208091
Recruitment Status : Completed
First Posted : September 21, 2005
Results First Posted : May 9, 2014
Last Update Posted : May 9, 2014
Solstice Neurosciences
Information provided by (Responsible Party):
Seth Pullman, Columbia University

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.

Condition or disease Intervention/treatment Phase
Focal Dystonia Drug: Botulinum toxin, type B Phase 4

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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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Evaluation of MIDI to Quantify Performance Change in Subjects With Musician's Dystonia After Treatment With Botulinum Toxin Type B (Myobloc ®).
Study Start Date : April 2003
Actual Primary Completion Date : May 2008
Actual Study Completion Date : May 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dystonia
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Botulinum toxin, type B
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.
Drug: Botulinum toxin, type B
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.
Other Name: Myobloc

Primary Outcome Measures :
  1. Note Errors (Related to Errors in Duration) [ Time Frame: Baseline and 6 weeks post-injection ]
    Note errors (related to errors in duration in msec) were obtained as measures of difference between the affected and unaffected hands--taking the musical instrument digital interface (MIDI) note output from four musical sequences of 8 to 16 notes played. It was calculated by averaging the sequences for each hand, and deriving the square root of the mean of the square of the differences (root mean square error, in msec) in MIDI.

  2. Note Errors (Related to Errors in Loudness) [ Time Frame: Baseline and 6 weeks post-injection ]
    Note errors (related to errors in loudness) were obtained as a measure of difference between the affected and unaffected hands--taking the musical instrument digital interface (MIDI) note loudness data (decibels) from four musical sequences of 8 to 16 notes. It was calculated by averaging sequences for each hand and taking the square root of the mean of the square of the differences (root mean square error, in decibels) in MIDI notes.

Secondary Outcome Measures :
  1. Subjective Assessment Ratings of Change [ Time Frame: Baseline to 6 weeks after injection ]
    Each subject assessed his or her music playing performance change subjectively from -100 percent (fully worse) to 100 percent (fully better).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   25 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Focal, task-specific dystonia clinically determined to be the result of a high level of musical skill and intensive performance history

Exclusion Criteria:

  • Neurological disorders other than dystonia
  • Patients who are clinically depressed, demented or otherwise unable to perform appropriately or sit through 1 hour of testing
  • Patients who have undergone pallidotomy, thalamotomy or deep brain stimulator implantations
  • Patients who have who recently have taken medications with extrapyramidal or tremorogenic side effects

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00208091

United States, New York
Neurological Institute, 710 W. 168th Street, NI-1112
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Solstice Neurosciences
Principal Investigator: Seth Pullman, MD Columbia University Medical Center, Department of Neurology

Responsible Party: Seth Pullman, Professor of Clinical, Department of Neurology, Movement Disorders, Columbia University Identifier: NCT00208091     History of Changes
Other Study ID Numbers: AAAB2808
First Posted: September 21, 2005    Key Record Dates
Results First Posted: May 9, 2014
Last Update Posted: May 9, 2014
Last Verified: April 2014

Keywords provided by Seth Pullman, Columbia University:
Botulinum Toxin Type B
Focal Dystonia
Muscle Relaxants
Motor Impairments
Motor Performance
Abnormal Postures

Additional relevant MeSH terms:
Dystonic Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Botulinum Toxins
Botulinum Toxins, Type A
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Anti-Dyskinesia Agents