Pathophysiology of Movement Disorders

Question 1

True/False. A greater number of CAG repeats is associated with earlier onset of Huntington’s disease.

Answer 1

True

Question 2

What mechanisms contribute to the pathogenesis of Parkinson’s disease?

Answer 2

Autooxidation of dopamine, mitochondrial dysfunction, excitotoxicity, immune mechanisms, gene mutations

Question 3

True/False. Multiple System Atrophy may be treated with levodopa.

Answer 3

False. The disease is unresponsive to levodopa.

Question 4

What is the genetic cause of familial Huntington’s Disease?

Answer 4

Mutations of the CAG repeats on chromosome 4 (most commonly paternal)

Question 5

This movement disorder is characterized by the loss of inhibitory GABAergic neurons in the striatum.

Answer 5

Huntington’s Disease

Question 6

This movement disorder presents with Parkinsonism, cerebellar dysfunction and autonomic dysfunctions, but NO dementia. What is it?

Answer 6

Multiple System Atrophy

Question 7

Corticobasal degeneration presents with “useless arm,” dementia, apraxia, “alien limb,” and hyperreflexia. What structures are affected that lead to this presentation?

Answer 7

Asymmetrical atrophy of the frontal and parietal lobes, loss of neurons in the substantia nigra, neurofibrillary tangles

Question 8

How does primary Parkinsonism differ from secondary Parkinsonism?

Answer 8

Primary Parkinsonism is a direct result of a genetic or brain disorder. Secondary Parkinsonism is secondary to another disorder, such as Wilson’s disease, head trauma, hydrocephalus, etc.

Question 9

What gene is highly mutated in familial Parkinson’s?

Answer 9

LRRK2 - encodes kinase

Question 10

What is the pathological cause of Progressive Supranuclear Palsy?

Answer 10

Accumulation of tau proteins

Question 11

What is one of the first clinical signs of Parkinson’s disease?

Answer 11

Loss of smell due to neuron loss in the olfactory region - Stage 5 of Pathogenesis

Question 12

These histological findings can confirm diagnosis of Parkinson’s disease, but are only visualized at autopsy.

Answer 12

Lewy Bodies

Question 13

What cells are most involved with immune reactions related to Parkinson’s disease?

Answer 13

Microglial cells - phagocytize melanin from apoptotic neurons

Question 14

Parkinson’s Disease is associated with the destruction of what brain structure?

Answer 14

Substantia nigra

Question 15

In Huntingon’s disease cells of the caudate and putamen (striatum) undergo apoptosis. What is the cellular trigger for this cell death?

Answer 15

Mitochondrial dysfunction due to caspase activation

Question 16

What are some characteristics that distinguish Lew Body Dementia?

Answer 16

Postural instability, visual hallucinations and delusions, negative reactions to antipsychotic drugs

Question 17

True/False. A diagnosis of Parkinsonism required a pre-existing diagnosis of Parkinson’s Disease.

Answer 17

False. Parkinsonism is a Parkinson’s-like disease, but is separate from Parkinson’s disease. A person may have Parkinsonism without having Parkinson’s disease.

Question 18

What is the composition of Lewy Bodies?

Answer 18

Buildup of alpha-synuclein proteins

Question 19

A patient presents to the clinic with an inability to look downward. As a result, they’ve fallen numerous times. Their head is also extended, with difficulty speaking and swallowing. What is a possible diagnosis?

Answer 19

Progressive Supranuclear Palsy

Question 20

What symptoms are associated with primary Parkinson’s Disease?

Answer 20

Bradykinesia, tremor at rest, muscle rigidity, ataxia