Quantifying Musical Performance After Treatment With Myobloc in Musician's Dystonia
Condition: Focal Dystonia
MeSH terms: Dystonia; Dystonic Disorders
Study type: Interventional
Phase: Phase 4

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

        1. Nutt JG, Muenter MD, Melton LJ, Aronson A, Kurland LT. Epidemiology of dystonia in
           Rochester, Minnesota. Adv Neurol 1988; 50: 361-5.

        2. Sheehy MP, Marsden CD. Writers' cramp - a focal dystonia. Brain 1982; 105: 461-480.

        3. Cohen LG, Hallett M. Hand cramps: clinical features and electromyographic patterns in a
           focal dystonia. Neurology 1988; 38: 1005-1012.

        4. Frucht S, Fahn S, Ford B. French horn embouchure dystonia. Mov Disord 1999; 14: 171-3.

        5. Oppenheim H. Uber eine eigenartige Krampfkrankheit des kindlichen und jungendichen
           Alters (dysbasia lordotica progressiva, dystonia musculorum deformans). Neurologie
           Centralblatt 1911; 30: 1090-1107.

        6. Fahn S. Concept and classification of dystonia. In Fahn, S, Marsden, CD, Caln, DB, ed.
           Advances in Neurology: Dystonia 2. New York: Raven Press, 1988: 1-8.

        7. Rothwell JC, Obeso JA, Day BL, Marsden CD. Pathophysiology of dystonias. In Desmedt, JE,
           ed. Advances in Neurology: Motor Control Mechanisms in Health and Disease. New York:
           Raven Press, 1983: 851-863.

        8. Marsden CD, Rothwell JC. The physiology of idiopathic dystonia. Can J Neurol Sci 1987;
           14: 521-527.

        9. Greene PE, Bressman S. Exteroceptive and interoceptive stimuli in dystonia. Mov Disord
           1998; 13: 549-51.

       10. Tempel L, Perlmutter J. Abnormal vibration-induced cerebral blood flow responses in
           idiopathic dystonia. Brain 1990; 113: 691-707.

       11. Kaji R, Rothwell JC, Katayama M, Tomoko I, Kubori T, Kohara N, Mezaki T, Shibasaki H,
           Kimura J. Tonic vibration reflex and muscle afferent block in writer's cramp. Ann Neurol
           1995; 38: 155-162.

       12. Koelman JHTM, Willemse RB, Bour LJ, Hilgevoord AAJ, Speelman JD, Ongerboer de Visser BW.
           Soleus H-reflex tests in dystonia. Mov Disord 1995; 10: 44-50.

       13. Pascual-Leone A. The brain that plays music and is changed by it. Ann N Y Acad Sci 2001;
           930: 315-29.

       14. Bressman SB, de Leon D, Kramer PL, Ozelius LJ, Brin MF, Greene PE, Fahn S, Breakefield
           XO, Risch NJ. Dystonia in Ashkenazi Jews: Clinical characterization of a founder
           mutation. Ann Neurol 1994; 36: 771-777.

       15. Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and
           reliability of a rating scale for the primary torsion dystonias. Neurology 1985; 35:
           73-77.

       16. Eidelberg D, Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Przedborski S, Fahn S. The
           metabolic topography of idiopathic torsion dystonia. Brain 1995; 118: 1473-1484.

       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.

       22. Trosch RM, Pullman SL. Botulinum toxin A injections for the treatment of hand tremors.
           Mov Disord 1994; 9: 601-9.
    

Intervention name(s): Botulinum toxin, type B
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Myobloc
Intervention MeSH terms: Botulinum Toxins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myloboc; Botulinum Toxin Type B; Focal Dystonia; Musicians; Muscle Relaxants; Motor Impairments; Motor Performance; Tremor; Abnormal Postures