Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00208091
Status:
COMPLETED
Last Update Posted:
2014-05-09
First Post:
2005-09-13
Brief Title:
Quantifying Musical Performance After Treatment With Myobloc in Musicians Dystonia
Sponsor:
Columbia University
Organization:
Columbia University
Study Overview
Official Title:
An Open Label Evaluation of MIDI to Quantify Performance Change in Subjects With Musicians Dystonia After Treatment With Botulinum Toxin Type B Myobloc
Status:
COMPLETED
Status Verified Date:
2014-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Writers 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 musicians 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 writers 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
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 Writers 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 musicians 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 writers 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None