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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.
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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 excessof movements or a paucity of movements, unrelated to weakness or spasticity
chorea dystonia myoclonus tics tremors akathisia ataxia athetosis ballism hyperekplexia moving toes / fingers myokymia myorhythmia restless legs stereotypy Excessof movements- Hyperkinesias -
pakinsonism apraxia cataplexy catatonia hypothyroid slowness stiff-muscles Paucity of movements- Hypokinesias -
BASAL GANGLIA CIRCUITRY GLU GLU Cerebral Cortex GLU GLU Striatum D2 D1 GLU GABA GABA GPe Thalamus DA SNc GABA GLU STN GLU GABA GPi/SNr excitatory inhibitory Brainstem Spinal Cord GLU GLU PPN
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
Treatment • Penicillamine • Neurologic worsening • Significant side effects • Trientine • Neurologic worsening • Zinc acetate • Tetrathiomolybdate • Liver transplantation • Symptomatic treatment of movement disorders