Dystonia: Cases Victor Fungdystonia usually looks indistinguishable from that in degenerative...
Transcript of Dystonia: Cases Victor Fungdystonia usually looks indistinguishable from that in degenerative...
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Dystonia: Cases
Movement Disorders Unit, Department of Neurology,Westmead Hospital & University of Sydney, Sydney, Australia
Victor Fung
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Acknowledgements• Movement Disorders Unit
– Sangamithra Babu– Florence Chang– Ainhi Ha– Mariese Hely (ret)– Samuel Kim– Ivan Lorentz (Emeritus)– Neil Mahant– John Morris (Emeritus)– Nigel Wolfe
– Russell Dale– Greg DeMoore– Shekeeb Mohammad– Michael Tchan
• Fellows– Alessandro Fois– Hugo Morales
Briceno
2016– Margaret Kit Kwan
Ma
• Nurses– Emma Everingham– Donna Galea– Jane Griffith– David Tsui
• Referring Neurologists– Peter Brimage– Paul Clouston– Paddy Grattan-
Smith– Mohammed Shaffi– Shaun Watson
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Learning Objectives
• At the conclusion of the activity, participantsshould be able to:
1. Identify a patient with movement disorders
2. Differentiate between Parkinson’s disease andatypical parkinsonism
3. Understand Movement Disorders through casediscussions
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Assessment of Dystonia:Clinical Challenges
• How to recognise dystonia?
• Dystonia due to secondary causes can looksimilar to idiopathic, non-degenerative disease
• How to know how far to go with investigations ineach patient presenting with dystonia
• How to make a specific aetiological or geneticdiagnosis
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Diagnostic approach in movement disorders
• Phenomenology– What kind(s) of involuntary movements are present?– What is the nature of any impairment of movement?
• Clinical syndrome– What mix of phenomenology is present?– What other neurological or systemic features are present?
• Aetio-Pathological diagnosis– What are the potential diseases that cause that syndrome?
• Genetic diagnosis
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• Phenomenology – “DYSTONIA”- What kind(s) of involuntary movements are present?- What is the nature of any impairment of movement?
• Syndromic diagnosis – “DYSTONIA”- What mix of phenomenology is present?- What other features are present?
• Aetio-Pathological diagnosis – “DYSTONIA”- What are the potential diseases that cause that
syndrome?
• Genetic diagnosis – “DYSTONIA”
The same term dystonia is usedfor differential levels
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• Phenomenology – “DYSTONIA”- What kind(s) of involuntary movements are present?- What is the nature of any impairment of movement?
• Syndromic diagnosis – “DYSTONIA”- What mix of phenomenology is present?- What other features are present?
• Aetio-Pathological diagnosis – “DYSTONIA”- What are the potential diseases that cause that
syndrome?
• Genetic diagnosis – “DYSTONIA”
Syndromic diagnosis in dystonia
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Dystonia is not a symptom…
• “I can’t ….”
• “My neck / arm / leg twists…”
• “My arm / leg cramps or spasms when I …”
• Stiffness / cramping / (pain)
• Tremor / involuntary movement
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• Dystonia is defined as a movement disordercharacterized by sustained or intermittent musclecontractions causing abnormal, often repetitive,movements, postures, or both.
• Dystonic movements are typically patterned andtwisting, and may be tremulous.
• Dystonia is often initiated or worsened byvoluntary action and associated with overflowmuscle activation.
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• Dystonia is defined as a movement disordercharacterized by sustained or intermittent musclecontractions causing abnormal, often repetitive,movements, postures, or both.
• Dystonic movements are typically patterned andtwisting, and may be tremulous.
• Dystonia is often initiated or worsened byvoluntary action and associated with overflowmuscle activation.
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Therapy of Movement Disorders: A Case-Based Approach. S Reich & S Factor (eds) Springer 2018
35 yo, R handed, normal birth & development, 1-2 yr h/oprogressive difficulty writing associated with pain over wrist
moreso than forearm. Negative FH.
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35 yo, R handed, normal birth & development, 1-2 yr h/oprogressive difficulty writing associated with pain over wrist
moreso than forearm. Negative FH.
Therapy of Movement Disorders: A Case-Based Approach. S Reich & S Factor (eds) Springer 2018
Writer’s cramp - adult onsettask-specific focal isolated dystonia
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Nov 2002
Apr 2004 Jan 2005
• 15 yo• idiopathic generalised isolateddystonia from age 5
“Dystonic movements aretypically patterned...”
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• 54 yo, 9/12 h/o R foot feeling as if it wanted to slip when standing,then progressive difficulty walking, worse on hard surfaces, betteron sand & grass, increasingly disabled.
2008
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• 54 yo, 9/12 h/o R foot feeling as if it wanted to slip when standing,then progressive difficulty walking, worse on hard surfaces, betteron sand & grass, increasingly disabled.
2008
Task-specific gait dystonia -Idiopathic lower limb isolated dystonia
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• Aug 2014: maintains 98% improvement since on tetrabenazine 12.5 dailycommenced Mar 2009. Previously worse with levodopa 300mg/day(needed crutches) and confused with benzhexol 3mg daily.
2014
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• 41yo, 2 yr h/o abnormal kicking of R leg when walking down stairs,slight feeling that R knee bends more walking up stairs, no problems
walking on flat. No h/o drug exposure. Normal MRI brain & spine.
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• 41yo, 2 yr h/o abnormal kicking of R leg when walking down stairs,slight feeling that R knee bends more walking up stairs, no problems
walking on flat. No h/o drug exposure. Normal MRI brain & spine.
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• 41yo, 2 yr h/o abnormal kicking of R leg when walking down stairs,slight feeling that R knee bends more walking up stairs, no problems
walking on flat. No h/o drug exposure. Normal MRI brain & spine.
Task-specific (downstairs) leg dystonia- adult onset focal isolated dystonia
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Courtesy Michael Hayes, Sydney, Australia
2016
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• 57yo, 17 yr h/o difficulty speaking
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• 57yo, 17 yr h/o difficulty speaking
Tongue dystonia(as part of task-specific oromandibular dystonia)
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73 yo, 12 mth h/o involuntary R ear movements, painful anddistressing, associated with R ant > post neck pain, intermittent
mild head tremor
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2006
• 22 yo, developmental delay and behavioural disturbance
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2008
• 22 yo, developmental delay and behavioural disturbance,treated with risperidone from 14 yo
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• Dystonia is defined as a movement disordercharacterized by sustained or intermittent musclecontractions causing abnormal, often repetitive,movements, postures, or both.
• Dystonic movements are typically patterned andtwisting, and may be tremulous.
• Dystonia is often initiated or worsened byvoluntary action and associated with overflowmuscle activation.
Can dystonia manifest as tremorwithout abnormal posturing?
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57 yo, 2 yr h/o involuntary twisting of neck to rightwith posterior right neck pain
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78 yo, 7 yr h/o head tremor, stable for last few years.
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39 yo, 12 yr h/o involuntary neck twitches associated withpost. neck pain, partly suppressed by touching chin or leaning
head back against wall
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81 yo, involuntary truncal movements lasting one week 4 and 2 yearsago, now persistent for 6 months. Distressing but not disabling,not present during walking. No medical or psychiatric history.
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22 yo with Wilson’s disease
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Focal isolated dystonia
• Adult onset focal isolated dystonia mostcommonly presents as cervical, cranial orupper limb dystonia
• Focal isolated dystonia can affect almost anypart of the body
• Look for patterned abnormal posture ormovement that may be task or position specific,or a geste antagoniste
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• The syndromes of late adult-onset focal isolateddystonia are usually sporadic without identifiablecause, and rarely progress to generalized dystonia,but can extend to contiguous body regions
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Isolated dystonia syndromes:Red flags
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Isolated dystonia syndromes:Role of imaging
• The phenomenology in idiopathic, non-degenerativedystonia usually looks indistinguishable from that indegenerative disease
• Most (but not all) dystonia secondary toneurodegenerative disease will have imagingabnormalities
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9 yo, onset generalised dystonia aged 2, parents first cousins
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7 yo, onset generalised dystonia aged 4,mother has cervical dystonia
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• 9 yo, onset generalised dystonia aged 2, parents first cousins
Pantothenate Kinase AssociatedNeurodegeneration (PKAN)
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• Phenomenology – “DYSTONIA”- What kind(s) of involuntary movements are present?- What is the nature of any impairment of movement?
• Syndromic diagnosis – “DYSTONIA”- What mix of phenomenology is present?- What other features are present?
• Aetio-Pathological diagnosis – “DYSTONIA”- What are the potential diseases that cause that
syndrome?
• Genetic diagnosis – “DYSTONIA”
Syndromic diagnosis in dystonia
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Combined dystonia syndromes
• Combined dystonia:– Dystonia + another movement disorder
+/- involvement of other neurological systems+/- systemic disease
• Combined dystonia is more likely to be due to aneurodegenerative process than isolated dystonia
• Many (but not all) combined dystonias due toneurodegenerative disease will have imagingabnormalities that provide a diagnostic clue
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2005(1/12 post-BTX1)
• 56 yo, 8 yr h/o intermittent head turn to R 3x/wk, 5 yr h/opersistent turn to R after waking from 45 min nap on a train.
Father with PD in 60’s.
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2005
• 56 yo, 8 yr h/o intermittent head turn to R 3x/wk, 5 yr h/opersistent turn to R after waking from 45 min nap on a train.
Father with PD in 60’s.
Axis I: Adult onset, focal isolated dystoniaAxis II: Sporadic, idiopathic
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2012
• 63 yo, 3 mthly BTX, 2-3 yr h/o increasing unsteadiness, no falls butusing stick. Her mother had “balance problems”, one of her sisters
diagnosed with orthostatic tremor, and another sister has adult onsetbalance and gait problems.
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2012
• 63 yo, 3 mthly BTX, 2-3 yr h/o increasing unsteadiness, no falls butusing stick. Her mother had “balance problems”, one of her sisters
diagnosed with orthostatic tremor, and another sister has adult onsetbalance and gait problems.
Axis I: Adult onset, focal dystonia combined withcerebellar syndrome
Axis II: Familial (autosomal dominant?), degenerative
• DYTCA(dystonia & cerebellar atrophy)– SCA 17– SCA 6– idiopathic
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2012
• 63 yo, 3 mthly BTX, 2-3 yr h/o increasing unsteadiness, no falls butusing stick. Her mother had “balance problems”, one of her sisters
diagnosed with orthostatic tremor, and another sister has adult onsetbalance and gait problems.
Axis I: Adult onset, focal dystonia combined withcerebellar syndrome
Axis II: Familial (autosomal dominant?), degenerative
• DYTCA(dystonia & cerebellar atrophy)– SCA 17– SCA 6– idiopathic
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Syndromes where minimalinvestigation are required
• Adult onset, focal isolated dystonia► Idiopathic, non-degenerative– Copper studies if
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Using investigations to define thesyndromic diagnosis
• Assessment of other neurological systems:– Radiological (MRI including iron susceptibility
sequences, CT for calcification)– Ophthalmological (slit lamp, retinal exam, ERG)– Neurophysiological (NCS/EMG, evoked potentials)
• Assessment of systemic involvement– Screening blood tests (haematological, hepatic,
renal, endocrine, copper studies)– Organ imaging
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• Phenomenology – “DYSTONIA”- What kind(s) of involuntary movements are present?- What is the nature of any impairment of movement?
• Syndromic diagnosis – “DYSTONIA”- What mix of phenomenology is present?- What other features are present?
• Aetio-Pathological diagnosis – “DYSTONIA”- What are the potential diseases that cause that
syndrome?
• Genetic diagnosis – “DYSTONIA”
Syndromic diagnosis in dystonia
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Investigations to make anaetiological or genetic diagnosis• Targeted metabolic analysis• Targeted genetic testing
• Wilson’s disease• Autoimmune screen (incl. cell surface Ab)• Leucocyte lysosomal enzymes• Urine metabolic screen screen (aminoacidurias,
urea cycle disorders and mucopolysaccharidoses)• CSF neurotransmitters, Glc, folate• Biopsy (muscle, skin, conjunctival, rectal)
• Genetic screening (Next Generation Sequencing)
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Genetic diagnosis of dystonia
• CGH microarray(large scale deletions or duplications)
• Dystonia gene panels(sequencing of lots of known dystonia genes)
• Whole exome sequencing
• Whole genome sequencing
• [ XXX Triplet repeat disorders XXX]
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Conclusions
• The assessment of dystonia requires asyndromic approach– Phenomenology– Syndromic diagnosis– Aetiological / Genetic differential diagnosis to
guide investigations
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2008
• 18yo, N milestones, 9/12 prior woke with speech impairment, L>Rslowness of hand movements and gait disturbance which partiallyrecovered. Stable since. MRI normal. No recreational drug, toxin or
medication exposure. No FH.
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• 19yo, sister of previous patient. Age 16, after EtOH++ & walking 2 hours, developed overhours imbalance, vertigo and generalised weakness. Woke next day with slurred speech,
UL limb stiffness & ongoing gait disturbance. Worst in the first 48 hours and then partiallyrecovered over days. Exacerbation during 3rd trimester of second pregnancy.
2017
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Videos courtesy of Dan Healy
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Expanding phenotypic spectrum ofATP1A3 mutations
• Rapid onset dystonia-parkinsonism
• CAPOS (cerebellar ataxia, areflexia, pes cavus, opticatrophy, sensorineural hearing loss )
• Alternating hemiplegia of childhood
• Catastrophic infantile epilepsy with microcephaly
• Fever-Induced paroxysmal weakness and encephalopathy(mutations at residue 756)
• Overlap syndromes with partial features