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