Neurological Manifestations of Wilson’s Disease

1. Neurological Manifestations of Wilson’s Disease Aleksandar Videnovic, MD, MSc Assistant Professor of Neurology Feinberg School of Medicine Northwestern University Chicago, IL

2. Samuel Alexnader Kinnier-Wilson 1912 - neurological disorder with progressive lenticular degeneration of the brain and cirrhosis of the liver

3. Epidemiology • 17 per million • carrier frequency 1 in 122

4. Clinical manifestations • Peak incidence – around 17 years • Rare after age 35, but present • Hepatic, neurologic and psychiatric manifestations

5. 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

6. MOVEMENT DISORDERS - definition - Neurological syndromes in which there is an excessof movements or a paucity of movements, unrelated to weakness or spasticity

7. chorea dystonia myoclonus tics tremors akathisia ataxia athetosis ballism hyperekplexia moving toes / fingers myokymia myorhythmia restless legs stereotypy Excessof movements- Hyperkinesias -

8. pakinsonism apraxia cataplexy catatonia hypothyroid slowness stiff-muscles Paucity of movements- Hypokinesias -

9. Abnormal movements - anatomy -

10. 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

11. 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

13. 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

15. Parkinsonism • Tremor • Slowness (bradykinesia) • Stiffness (rigidity) • Unsteady gait • In 19-62% of neurologic WD 1 1 Taly et al. 2007

16. Parkinsonism • Resting tremor

17. Parkinsonism • Bradykinesia

18. 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

20. Dysarthria • Probably the most common neurologic manifestation • In 85-97% of neurologic WD 1 • Mixed type dysarthria 1 Machado et al. 2006

21. Cognition • Cognitive impairment may be saddle • Most commonly: • Impulsivity • Impaired social judgment • Apathy • Decreased attention • Executive dysfunction • Emotional lability

22. Kayser – Fleischer (KF) Rings • seen in nearly 100% of neurologic WS 1 Lorinz et al. 2009

23. 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

24. Differential diagnosis of neurologic WD • Essential tremor • Young-onset Parkinson’s disease • Dystonia • Huntington disease • Benign familial chorea

25. Brain imaging in neurologic WD

26. Treatment • Penicillamine • Neurologic worsening • Significant side effects • Trientine • Neurologic worsening • Zinc acetate • Tetrathiomolybdate • Liver transplantation • Symptomatic treatment of movement disorders