Transcript the PowerPoint Presentation

Neurological Manifestations of Wilson’s
Disease
Aleksandar Videnovic, MD, MSc
Assistant Professor of Neurology
Feinberg School of Medicine
Northwestern University
Chicago, IL
Samuel Alexnader Kinnier-Wilson
1912 - neurological disorder with progressive lenticular
degeneration of the brain and cirrhosis of the liver
Epidemiology
• 17 per million
• carrier frequency 1 in 122
Clinical manifestations
• Peak incidence – around 17 years
• Rare after age 35, but present
• Hepatic, neurologic and psychiatric manifestations
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
MOVEMENT DISORDERS
- definition -
Neurological syndromes in which there is
an excess of movements or
a paucity of movements,
unrelated to weakness or spasticity
Excess of movements
- Hyperkinesias -
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chorea
dystonia
myoclonus
tics
tremors
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akathisia
ataxia
athetosis
ballism
hyperekplexia
moving toes / fingers
myokymia
myorhythmia
restless legs
stereotypy
Paucity of movements
- Hypokinesias -
• pakinsonism
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apraxia
cataplexy
catatonia
hypothyroid slowness
stiff-muscles
Abnormal movements
- anatomy -
BASAL GANGLIA CIRCUITRY
GLU
GLU
Cerebral Cortex
GLU
GLU
Striatum
D2
D1
GLU
GABA
GABA
GPe
Thalamus
DA
GABA
GLU
SNc
STN
GLU
GPi/SNr
Brainstem
Spinal Cord
GABA
excitatory
GLU
GLU
PPN
inhibitory
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
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Machado et al. 2006;
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Oder et al. 1991; 3 Taly et al. 2007
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
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Walshe et al. 1992;
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Slotanzadeh et al. 2007
Parkinsonism
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Tremor
Slowness (bradykinesia)
Stiffness (rigidity)
Unsteady gait
• In 19-62% of neurologic WD 1
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Taly et al. 2007
Parkinsonism
• Resting tremor
Parkinsonism
• Bradykinesia
Chorea
• involuntary, irregular, purposeless, non-rhythmic, abrupt, rapid, unsustained 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
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Machado et al. 2006;
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Oder et al. 1991; 3 Taly et al. 2007
Dysarthria
• Probably the most common neurologic manifestation
• In 85-97% of neurologic WD 1
• Mixed type dysarthria
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Machado et al. 2006
Cognition
• Cognitive impairment may be saddle
• Most commonly:
– Impulsivity
– Impaired social judgment
– Apathy
– Decreased attention
– Executive dysfunction
– Emotional lability
Kayser – Fleischer (KF) Rings
• seen in nearly 100% of neurologic WS
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Lorinz et al. 2009
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
Differential diagnosis of neurologic WD
• Essential tremor
• Young-onset Parkinson’s disease
• Dystonia
• Huntington disease
• Benign familial chorea
Brain imaging in neurologic WD
Treatment
• Penicillamine
• Neurologic worsening
• Significant side effects
• Trientine
• Neurologic worsening
• Zinc acetate
• Tetrathiomolybdate
• Liver transplantation
• Symptomatic treatment of movement disorders