LIMB DYSTONIA HISTORY, PHENOMENOLOGY, EVALUATION, TREATMENT · limb dystonia history,...

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LIMB DYSTONIA HISTORY, PHENOMENOLOGY, EVALUATION, TREATMENT Mark F. Lew, MD Professor of Neurology Vice-chair Department of Neurology Vandermeulen Chair in PD Research Director Division of Movement Disorders KECK/USC School of Medicine Los Angeles, CA

Transcript of LIMB DYSTONIA HISTORY, PHENOMENOLOGY, EVALUATION, TREATMENT · limb dystonia history,...

Page 1: LIMB DYSTONIA HISTORY, PHENOMENOLOGY, EVALUATION, TREATMENT · limb dystonia history, phenomenology, evaluation, treatment ... unclear if sensori-motor abnormalities ... sohn yh,

LIMB DYSTONIA HISTORY,

PHENOMENOLOGY,

EVALUATION, TREATMENT

Mark F. Lew, MDProfessor of Neurology Vice-chair Department of Neurology

Vandermeulen Chair in PD Research

Director Division of Movement Disorders

KECK/USC School of Medicine

Los Angeles, CA

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Disclosures

Advisor/Consultant: AbbVie Inc., Acadia Pharmaceuticals, Inc., Adamas Pharmaceuticals, Inc., Auspex Pharmaceuticals, Cynapsus Therapeutics, Inc., Impax Laboratories, Inc., Lundbeck, TevaPharmaceuticals, UCB, and US WorldMeds LLC.

Speaker’s Bureau participant: Acadia Pharmaceuticals, Inc., Impax Laboratories, Inc., Lundbeck, TevaPharmaceuticals, UCB, and US WorldMeds LLC.

Research funding; the Parkinson’s Study Group, Michael J. Fox Foundation, Civitas Therapeutics, Inc., BiotieTherapies, Cynapsus Therapeutics, Inc., IntecPharma, Neuroderm, and the National Institutes of Health.

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LIMB DYSTONIA

GENERAL DEFINITION

DYSTONIA IS CHARACTERIZED BY SUSTAINED MUSCLE CONTRACTIONS FREQUENTLY CAUSING REPETITIVE TWISTING MOVEMENTS OR ABNORMAL POSTURES

PREVALENCE ESTIMATES OF DYSTONIA VARY: 2.7/1,000,000 ROCHESTER MINNESOTA

11.1/100,000 ASHKENAZI JEWISH NYC

60/100,000 LATE ONSET NEW ENGLAND

300/100,000 LATE ONSET ITALY >50yo

Defazio G, et al. The Lancet Neurology. 2004; 3(11): 673-678.

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DYSTONIA BY TOPOGRAPHY

Tarsy D, et al. N Engl J Med. 2006; 355:818-829.

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FOCAL DYSTONIA: AGE OF ONSET

DYT-111.3 yrs

WC38.4

CD40.8

SD43.0

Bleph-oromand55.7

O’Riordan S, et al. Neurology 2004;63:1423-1426.

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FOCAL DYSTONIAS

Tarsy D, et al. N Engl J Med. 2006; 355:818-829.

.

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Tarsy D, et al. N Engl J Med. 2006;

355:818-829.

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LIMB DYSTONIA:PHENOMENOLOGY

MOST COMMON FORM IS WRITER’S CRAMP

INVOLUNTARY HAND POSTURES IMPAIR WRITING

UNDERESTIMATED AS PATIENTS DON’T SEEK

MEDICAL ADVICE

MALE PREDOMINANCE

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CASE PRESENTATION

53 Y/O RH FEMALE WITH 3 YRS OF PROG

DIFF WRITING

NO DIFFICULTY USING HER HANDS FOR

OTHER TASKS

NO CRAMPING, SPASM, OR INVOLUNTARY

MVMT ELSEWHERE

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WRITERS CRAMP VIDEO

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TREATMENT

ONABOTULINUM TOXIN INJECTED AS

FOLLOWS WITH EMG GUIDANCE:

– 5 U R EXT INDICES PROPRIUS

– 5 U R EXT DIGITORUM COMMUNIS (FASCICLE

FOR MIDDLE FINGER)

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EXTENSOR INDICES PROPRIUS (9)

EXTENSOR DIGITORUM COMMUNIS (7)

Perotto A. Anatomical Guide For The Electromyographer. 1994: p42-45.

Mcminn RMH, et al. Color atlas of human anatomy. 1977: p127.

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LIMB DYSTONIA

HISTORY

DESCRIPTIONS BACK TO 18TH CENTURY

WITH SCRIBES REPORTING CRAMPING OF

HANDS ONLY WHEN PERFORMING THEIR

JOBS

ABLE TO PERFORM VIRTUALLY ALL OTHER

TASKS NORMALLY

“OCCUPATIONAL PALSY”

Albanese A. et al. Mov Disord. 2013 Jun 15; 28(7): 863-873.

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LIMB DYSTONIA

WHAT IS IT???

REPRESENTS A FOCAL/TASK SPECIFIC DYSTONIA

UNCLEAR RELATIONSHIP TO PERIPHERAL/CENTRAL TRAUMA

ABERRANT PLASTICITY FROM EXCESSIVE, REPETITIVE USE

LIKELY THAT DISORDER IS A CONSEQUENCE OF REPETITIVE ACTIVITY ON BACKGROUND OF A GENETIC PREDISPOSITION

Furuya S, et al. Neurosci Res. 2016;104:112-119.

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LIMB DYSTONIA

TASK SPECIFIC DYSTONIA

MAY OCCUR DURING SKILLED MANUAL

ACTIVITIES “OCCUPATIONAL CRAMPS”

OTHER DESCRIPTIONS INCLUDE STRING

MUSICIANS, PIANISTS,TYPISTS, TYPESETTERS,

SURGEONS

DIS-SIMILAR FROM ORTHOPEDIC OVER-USE

SYNDROMES AS DOES NOT IMPROVE WITH

REST

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LIMB DYSTONIA

PATHOPHYSIOLOGY IMPAIRED INHIBITION AT MULTIPLE LEVELS OF THE

CNS

HALLETT ET AL DISTURBED SURROUND INHIBITION

WITH FAILURE TO SURPRESS NEURONAL

EXCITABILITY IN REGIONS SURROUNDING

ACTIVATED NEURAL CIRCUITS MAY CAUSE

OVERFLOW MOVEMENTS IN ADJACENT MUSCLES

SENSORIMOTOR REPRESENTATION OF AFFECTED

BODY PARTS IS ENLARGED IN THE CEREBRAL

CORTEX OF PATIENTS WITH FOCAL DYSTONIA

UNCLEAR IF SENSORI-MOTOR ABNORMALITIES

ARE PRIMARY OR SECONDARY???

Sohn YH, Hallett M. ANN NEUROL. 2004:OCT;56(4):595-599.

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LIMB DYSTONIA

PATHOPHYSIOLOGY (TMS)

“IN CONCLUSION THESE FINDINGS FROM REACTION TIME TASKS IN PATIENTS WITH PRIMARY DYSTONIA PROVIDE EVIDENCE OF ABNORMAL PRE-MOVEMENT MOTOR CORTEX EXCITABILITY. THE ABNORMALITY IS DUE TO AN ALTERED RELEASE OR RUNNING OF MOTOR PROGRAMS.”

Gilio F, et al. Brain. 2003 Aug;126(Pt 8):1745-1754.

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LIMB DYSTONIA

PATHOPHYSIOLOGY

“ In writers camp we found that HFO patterns are strongly decreased in power and disorganized in time This supports the assumption that abnormal HFOs reflect pathophysiological mechanisms occurring in focal dystonia, possibly resulting from a dysfunction of somatosensory processing”

Cimatti Z, et al. Brain. 2007 Jan;130(Pt 1):198-205.

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DISRUPTED SOMATOTOPY OF THE FINGERS IN

THE SOMATOSENSORY CORTEX IN

FOCAL HAND DYSTONIA

Meunier S, et al. Ann Neurol. 2001;50:521-527.

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LIMB DYSTONIA

DIFFERENTIAL DIAGNOSIS EPISODIC

– TETANY, OTHER METABOLIC CHANGES

• LOW CALCIUM, MAGNESIUM, GLUCOSE, HYPERVENTILATION

– MYOTONIA

– FOCAL EPILEPSY, INCLUDING FRONTAL LOBE SEIZURES

– TONIC SPASMS

PERSISTENT

– GROWTH DEFORMITY, DUPUYTREN’S CONTRACTURE

– ARTHRITIS, REPETITIVE STRAIN INJURY, CRPS

– UMN OR LMN LESION

• CARPAL TUNNEL SYNDROME

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LIMB DYSTONIA

DIFFERENTIAL DIAGNOSIS

DIFFERENTIAL DIAGNOSIS OF PARKINSON’S DISEASE,

ATYPICAL PARKINSONIAN SYNDROMES/MULTIPLE

SYSTEM ATROPHY MUST BE CONSIDERED IN

PATIENTS OF APPROPRIATE AGE WITH FOOT/LEG

DYSTONIA

YOUNGER PATIENTS DYT1/PTD

NEED TO CONSIDER PERIPHERAL NERVE

INJURY/ENTRAPMENT BASED ON EXAM

OVERUSE SYNDROMES, TASK SPECIFIC TREMORS

MUST R/O STRUCTURAL LESION

THALAMUS/PUTAMEN WITH NEUROIMAGING/CAREFUL

NEUROLOGIC EXAM

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Bhatia KP, Marsden CD. Brain. 1994 Aug;117 ( Pt 4):859-876.

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LIMB DYSTONIA

STRUCTURAL LESION

Münchau A, et al. J Neurol Neurosurg Psychiatry. 2000 Oct;69(4):494-498.

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LIMB DYSTONIA

STRUCTURAL LESION

10/16 CASES WITH HEMI- DYSTONIA

Lee MS, Marsden CD. Mov Disord. 1994 Sep;9(5):493-507.

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THALAMIC

INFARCT

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LIMB DYSTONIA

DIFFERENTIAL DIAGNOSIS

LIMB DYSTONIA AS AN EARLY SIGN IN PSP 8/30 CASES

Rafal RD, Friedman JH. Neurology. 1987 Sep;37(9):1546-1549.

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LIMB DYSTONIA

DIFFERENTIAL DIAGNOSIS

5/24 MSA PTS PRESENTED WITH LIMB DYSTONIA

Boesch SM, et al. J Neurol Neurosurg Psychiatry. 2002 Mar;72(3):300-303.

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LIMB DYSTONIA

GENETICS

THREE PTS WITH MUSICIAN’S DYSTONIA 7 RELATIVES WITH WRITER’S CRAMP

Schmidt A, et al. Neurology. 2006 Aug 22;67(4):691-693.

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CASE PRESENTATION

49 Y/O VIOLONIST WITH 2 YEARS OF INVOL

FLEXION OF LEFT 4TH AND 5TH FINGER

WHILE PLAYING VIOLIN

NO MVMT ELESEWHERE

ONLY OCCURS WHILE PLAYING VIOLIN

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MUSICIANS DYSTONIA

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KEYBOARD DYSTONIA

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TREATMENT

ONABOTULINUM TOXIN INJECTED AS

FOLLOWS WITH EMG GUIDANCE:

– 5 U FLEXOR DIGITORUM SUPERFICIALIS

– 5 U FLEXOR DIGITORUM PROFUNDUS

INTO APPROPRIATE FINGER FASCICLES

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FLEXOR DIGITORUM SUPERFICIALISPIP FLEXION

FLEXOR DIGITORUM PROFUNDUSDIP FLEXION

Perotto A. Anatomical Guide For The Electromyographer.

1994: p56-59.

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LIMB DYSTONIA

NEUROLOGIC EVALUATION 1

IDENTIFY AND CAREFULLY DESCRIBE THE DYSTONIA:

– BODY REGION(S) INVOLVED, SEVERITY, SPREAD AT REST,

DURING TASKS THAT ELICIT DYSTONIA AND ANY

MODULATING FACTORS

– SORT OUT COMPENSATORY MOVEMENTS AND SENSORY

TRICKS FROM PRIMARY PATTERN OF DYSTONIA

TAKE INTO ACCOUNT:

– DETAILED SUBJECTIVE HISTORY OF COMPLAINT

– PALPATE LIMB DURING ABNORMAL MOVEMENT

– EMG ASSISTANCE IN IDENTIFYING AREAS OF EXCESSIVE

MUSCLE ACTIVITY

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LIMB DYSTONIANEUROLOGIC EVALUATION 2

THOROUGH NEUROLOGIC EVALUATION/EXAM

– PARTICULARLY PARKINSONIAN FEATURES, SPASTICITY, LOCALIZING PERIPHERAL NERVE OR ROOT ABNORMALITIES

– EMG/NCS FREQUENTLY ORDERED

– CNS NEUROIMAGING ( BASAL GANGLIA/THALAMUS)

– FURTHER STUDIES AS CLINICALLY WARRANTED

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CASE PRESENTATION

68 Y/O CF W/ 8 YR HX OF FOOT CRAMPING

AND INVOLUNTARY MOVEMENTS OF HER

TOES ON WALKING

EVAL BY PODIATRY- MANY SURGERIES

W/OUT IMPROVEMENT

INTERFERED WITH WALKING BUT O/W

QUIESCENT

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FOOT DYSTONIA

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TREATMENT

TRIALS OF ONABOTULINUM TOXIN VIA EMG GUIDANCE OFFERED NO BENEFIT ON MULTIPLE OCCASIONS

FLEXOR DIGITORUM BREVIS, LONGUS-10U INTO DIGIT 3+4, FLEXOR HALLUCIS LONGUS 10U, FLEXOR HALLUCIS BREVIS 5U

TREATED WITH PT, FOOT ORTHOTIC AND ORAL MEDICATIONS

LORAZEPAM .5MG TID, LIORESAL 5 MG TID, TRIHEXYPHENIDYL 2 MG BID

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FLEX DIG BREVIS

FLEX HAL BREVIS

FLEX HAL LONGUS FLEX DIG LONGUS

Perotto A. Anatomical guide for the electromyographer. 1994:

p130-149.

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46YO WITH R FOOT DYSTONIA AND RUE

COGWHEEL RIGIDITY

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LIMB DYSTONIA

TREATMENT

ROUTINE THERAPIES INCLUDE A

MULTIDISCIPLINARY EVALUATION WITH

OCCUPATIONAL HAND THERAPIST FOR

POTENTIAL RETRAINING AND USE OF

WRITING DEVICES

UNFORTUNATELY ABOUT 50% WHO

SWITCH TO USING THE UNAFFECTED/NON-

DOMINANT SIDE DEVELOP SIMILAR

DYSTONIA/WC

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LIMB DYSTONIA

TREATMENT

MEDICATIONS INCLUDING ANTICHOLINERGICS, BENZODIAZEPINES, ETC.

EMG GUIDED BOTULINUM TOXIN INJECTIONS. LITERATURE PREDICTS FLEXION AND PRONATION RESPOND BEST, TREMOR POOR RESPONSE

SENSORIMOTOR RE-TRAINING

LITERATURE SUGGESTS LIMB IMMOBILIZATION FOR 5 WEEKS,SENSORY TRAINING (LEARNING BRAILLE),LOW FREQUENCY, REPETITIVE TMS

Zeuner KE, Molloy FM. NeuroRehabilitation. 2008;23(1):43-53.

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PENAGAIN

WRITER’S CRAMP

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LIMB DYSTONIA

TREATMENT

Baur B, et al. Hum Mov Sci. 2006 Oct;25(4-5):464-473.

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LIMB DYSTONIA

TREATMENT

Zeuner KE, et al. Mov Disord. 2005 Mar;20(3):335-341.