Pathology of Movement Disorders

Question 1

Parkinsonism vs. Hyperkinetic disorders

Answer 1

Parkinsonism disorders characterized by “cogwheel” rigidity, bradykinesia, and resting tremor–caused by damage to nigrostriatal dopaminergic system of the basal ganglia.

Hyperkinetic disorders involve chorea, excessive uncontrolled movements.

Question 2

Parkinson Disease

Clinical vs. definitive diagnosis

Microscopic findings

Etiology

Answer 2

Clinical diagnosis includes positive parkinsonian signs and response to L-DOPA with no evidence of PD mimics. Definitive diagnosis involves classic pathological findings on autopsy (loss of substantia nigra in midbrain, decreased pigmentation in locus ceruleusin in pons) and presence of Lewy bodies.

Microscopic findings include cortical Lewy bodies (abnormal deposits of alpha-synuclein) and “wormy” neurites.

Most cases are sporadic. Hereditary forms rare.

Question 3

How to differentiate dementia with Lewy bodies vs. Parkinson’s Disease with dementia?

Answer 3

Pathologically, both would look the same–what is key is knowing time of dementia onset.

With dementia with Lewy bodies, dementia precedes movement disorder. In PD dementia, movement disorder precedes dementia.

Question 4

What is multiple system atrophy? Different subsets?

Answer 4

A group fo neurodegenerative disorders with GLIAL cytoplasmic inclusions of alpha synuclein.

MSA-P (Parkinsonism) - striatonigral degeneration
MSA-C (cerebellar dysfunction/ataxia) –> olivopontocerebellar atrophy (OPCA)
MSA-A (dysautonomia) –> Shy-Drager syndrome

Question 5

Features of MSA-P

Answer 5

RAPIDLY progressive parkinsonism with symptoms of dysphagia and/or postural instability within few years of motor onset. Death usually due to bulbar dysfunction.

POOR L-DOPA response, as opposed to Parkinson Disease.

Question 6

Progressive Supranuclear Palsy

Microscopic findings

Answer 6

Parkinsonism and extra-pyramidal symptoms –> supranuclear ophthalmoplegia (vertical gaze palsy), mild progressive dementia

A TAU-opathy so would see globose TAU “tangles” and tufted astrocytes due to TAU accumulations. “Hummingbird’s sign”

Question 7

Coritcobasal Degeneration (CBD)

Microscopic findings

Answer 7

TAU-opathy with cortical and extra-pyramidal symptoms with three phases of illness:

1) Asymmetric clumsiness
2) Parkinsonism, “alien hand”, sensory cortical dysfunctions
3) Cognitive decline

Would see “ballooned” neurons in cortex, as well as frontocortical atrophy and TAU tangles.

Question 8

Huntington Disease

Etiology
Clinical features
Gross and microscopic findings

Answer 8

Autosomal dominant –> compared to other movement disorders where majority are sporadic. Expansion of CAG repeat, resulting in abnormal Hungtintin protein (toxic gain of function) and features of anticipation.

Progressive disease with features of chorea, psychiatric symptoms, and LATE onset cognitive decline that leads to dementia.

Gross findings: striatal atrophy (caudate and putamen), large lateral ventricles from hydrocephalus

Microscopic findings: severe neuronal loss (medium spiny neurons), astrocytosis in striatum. Staining for ubiquitin reveals pathological accumulation of huntingtin protein as intranuclear inclusions or in neurites.

Question 9

Wilson Disease

Etiology
Clinical features
Lab findings
Gross and microscopic findings

Answer 9

Autosomal recessive defect in copper transporting ATPase, resulting in accumulations in brain, liver, etc.

Liver failure cirrhosis in early childhood, neurologic disease later. Kaiser-Fleischer rings in eyes (Descemet’s membrane of cornea).

Decreased ceruloplasmin (copper transporter).

Basal ganglia atrophy/cavitation

Neuronal loss, astrocytosis, Alzheimer’s type II astrocytes