Neurological Manifestations of Wilson’s Disease Aleksandar Videnovic, MD, MSc Assistant Professor...
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Transcript of Neurological Manifestations of Wilson’s Disease Aleksandar Videnovic, MD, MSc Assistant Professor...
Neurological Manifestations of Wilson’s Disease
Aleksandar Videnovic, MD, MSc
Assistant Professor of NeurologyFeinberg School of Medicine
Northwestern UniversityChicago, 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 -
• chorea• dystonia• myoclonus• tics• tremors
• akathisia• ataxia• athetosis• ballism• hyperekplexia• moving toes / fingers• myokymia• myorhythmia• restless legs• stereotypy
Paucity of movements- Hypokinesias -
• pakinsonism
• apraxia• cataplexy• catatonia• hypothyroid slowness• stiff-muscles
Abnormal movements - anatomy -
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
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
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
Parkinsonism
• Tremor• Slowness (bradykinesia)• Stiffness (rigidity)• Unsteady gait
• In 19-62% of neurologic WD 1
1 Taly et al. 2007
Parkinsonism
• Resting tremor
Parkinsonism
• Bradykinesia
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
Dysarthria
• Probably the most common neurologic manifestation
• In 85-97% of neurologic WD 1
• Mixed type dysarthria
1 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
1 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