0917 - Neurodegenerative Diseases

Question 1

Define neurodegenerative disease and discuss their importance in medicine.

Answer 1

Abnormal protein variants that cause loss of function or aggregation and toxic gain of function, leading to gliosis from degeneration of neurons and synapses.

Characteristics are a progressive loss of neurons in previously healthy patients leading to grey matter changes in a selective pattern. There is development of intraneuronal protein aggregates which are resistant to degradation and are cytotoxic to neurons.

Important because they severely affect self-care and independence and so require community support. Treatment can be multifocal and long-term, and significant research is still ongoing.

Question 2

Discuss and identify the pathological features of Alzheimer’s disease

Answer 2

Cortical degenerative disease leading to progressive and widespread loss of cognitive function.

Cortical atrophy with narrowed gyri and widened sulci.

Neuritic Plaques - pink blobs on H&E, sometimes surrounded by halo with astrocytes and microglia at periphery.

Neurofibrillary Tangles - Flame-shaped pattern with intracellular bundles of tau filament tangles that encircle or displace nucleus, and may persist as ‘ghosts’ after neuron death.

Amyloid angiopathy - thickening of vessel wall with pink material (amyloid) build up in the wall.

Question 3

Discuss and identify the pathological features of Parkinson’s Disease

Answer 3

Decreased dopaminergic effect on striatum. Paleness of locus coerullus, substantia nigra and softening of the area reflecting neuronal loss. H&E shows loss of neuromelanin due to loss of dopaminergic pigmented neurons. Remaining neurons have Lewy bodies near neuromelanin - round pink inclusions in cytoplasm.

Question 4

Discuss and identify the pathological features of Huntington’s disease

Answer 4

Genetic CAG repeat on chromosome 4 in area coding for Huntingtin.

Degeneration of striatal neurons, leading to hyperkinetic disorder.

Atrophy of caudate and putamen, and widespread cerebral atrophy (continue)

Question 5

Discuss and identify the pathological features of ALS

Answer 5

Destruction and loss of upper and lower motor neurons, with denervation and atrophy of corresponding muscles.

Motor neurons shrink.

Presence of spheroids - focal accumulations of neurofilamients.

Neurogenic muscle atrophy (amyotrophy).

Question 6

What is a typical clinical presentation of Alzheimer’s Disease?

Answer 6

Dementia - progressive loss of cognitive function affecting thought content, perception, affect, behaviour, memory, and personality.

Question 7

What is a typical clinical presentation of Parkinson’s Disease?

Answer 7

TRAP - Tremor, Rigidity, Akinesia, Postural instability. More common with increasing age.

Question 8

What is a typical clinical presentation of Huntington’s Disease?

Answer 8

Insidious onset - 35-45 years but with anticipation.

Chorea - arrhythmic involuntary movements that are typically sudden and brief and seem to flow from one part of the body to another.

Dementia

Emotional Symptoms

Parkinsonism (sometimes)

Depression

Question 9

What is a typical clinical presentation of ALS?

Answer 9

Fasciculations

Progressive loss of voluntary contraction and wasting and atrophy of affected muscles.

Difficulty with chewing, swallowing and movements of face and tongue.

Progressive physical disability but mental functions and physical sensation are spared.