neurological manifestations of wilson’s disease aleksandar videnovic, md, msc assistant professor...
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Neurological Manifestations of Wilson’s Disease
Aleksandar Videnovic, MD, MSc
Assistant Professor of NeurologyFeinberg School of Medicine
Northwestern UniversityChicago, IL
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Samuel Alexnader Kinnier-Wilson
1912 - neurological disorder with progressive lenticular degeneration of the brain and cirrhosis of the liver
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Epidemiology
• 17 per million
• carrier frequency 1 in 122
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Clinical manifestations
• Peak incidence – around 17 years
• Rare after age 35, but present
• Hepatic, neurologic and psychiatric manifestations
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Neurologic manifestations
• Onset of neurological symptoms – about 15-21 yrs of age
• Initial presenting symptoms in 18-68% of diagnosed WD patients
• One or combination of several neurologic symptoms / signs
• Most common - a movement disorder
Lorinz et al. 2009; Brewer 2005
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MOVEMENT DISORDERS - definition -
Neurological syndromes in which there is
an excess of movements or
a paucity of movements,
unrelated to weakness or spasticity
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Excess of movements- Hyperkinesias -
• chorea• dystonia• myoclonus• tics• tremors
• akathisia• ataxia• athetosis• ballism• hyperekplexia• moving toes / fingers• myokymia• myorhythmia• restless legs• stereotypy
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Paucity of movements- Hypokinesias -
• pakinsonism
• apraxia• cataplexy• catatonia• hypothyroid slowness• stiff-muscles
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Abnormal movements - anatomy -
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Cerebral Cortex
StriatumD2 D1
GPe
SNc
STN
Thalamus
GPi/SNr
PPN
BrainstemSpinal Cord
GLU
GLU
GLUGABA
GLU GLU
GABA
DA
GLU
GLU
GLU
GLU
GABA
excitatory
inhibitory
GABA
BASAL GANGLIA CIRCUITRY
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Dystonia
• A neurological syndrome characterized by involuntary, patterned, sustained, or repetitive muscle contractions of opposing muscles, causing twisting movements and abnormal postures
• In 11-65% of neurologic WD 1-3
• Focal, segmental, multifocal, generalized
1 Machado et al. 2006; 2 Oder et al. 1991; 3 Taly et al. 2007
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Tremor
• In 22-55% of neurologic WD 1,2
• Can occur at rest, with posture or action
• “wing-beating” tremor
• May be confused with essential tremor
1 Walshe et al. 1992; 2 Slotanzadeh et al. 2007
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Parkinsonism
• Tremor• Slowness (bradykinesia)• Stiffness (rigidity)• Unsteady gait
• In 19-62% of neurologic WD 1
1 Taly et al. 2007
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Parkinsonism
• Resting tremor
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Parkinsonism
• Bradykinesia
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Chorea
• involuntary, irregular, purposeless, non-rhythmic, abrupt, rapid, un-sustained movements that seem to flow from one body part to another
• In 6-16% of neurologic WD 1-3
• Mainly in young-onset disease
• Rarely isolated, usually together with other involuntary movements
1 Machado et al. 2006; 2 Oder et al. 1991; 3 Taly et al. 2007
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Dysarthria
• Probably the most common neurologic manifestation
• In 85-97% of neurologic WD 1
• Mixed type dysarthria
1 Machado et al. 2006
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Cognition
• Cognitive impairment may be saddle
• Most commonly:– Impulsivity– Impaired social judgment– Apathy– Decreased attention– Executive dysfunction– Emotional lability
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Kayser – Fleischer (KF) Rings
• seen in nearly 100% of neurologic WS
1 Lorinz et al. 2009
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Natural history of neurologic WD
• Mean age of onset -15-21 yeas of age
• Variable clinical course
• Fluctuations are common
• Tremor-predominant disease may have somewhat slower course relative to dystonic forms
• Younger patients – dystonia and chorea
• Older patients - tremor
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Differential diagnosis of neurologic WD
• Essential tremor
• Young-onset Parkinson’s disease
• Dystonia
• Huntington disease
• Benign familial chorea
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Brain imaging in neurologic WD
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Treatment
• Penicillamine • Neurologic worsening• Significant side effects
• Trientine• Neurologic worsening
• Zinc acetate• Tetrathiomolybdate• Liver transplantation
• Symptomatic treatment of movement disorders