Huntington’s & Parkinson’s Disease (Theme D)

Question 1

PD is a what type of (basal ganglia) movement disorder?

Answer 1

Hypokinetic

Question 2

HD is a what type of (basal ganglia) movement disorder?

Answer 2

Hyperkinetic

Question 3

What is the impact of neurodegeneration of dopaminergic neurones in the substansia nigra in PD?

Answer 3

Loss of fibres that stimulate D1 & D2 receptors
This leads to increase of inhibitory outflow from basal ganglia - resulting in less stimulation of motor cortical regions

Question 4

What is the pathophysiology of PD?

Answer 4

Neurodegeneration of dopaminergic neurones in the substansia nigra

Formation of Lewy bodies (made up of the protein alpha-synuclein)

Question 5

What are the motor symptoms of PD?

Answer 5

Resting tremor
Bradykinesia (slowness of movement)
Akinesia (inability to make movement)
Rigidity
Mask-like faces - i.e., loss of facial expressions
Postural instability

Question 6

What is the name of the D1/D2 receptor agonist that has been shown to have amazing results in parkinsonian patients?

Answer 6

Apomorphine

Question 7

What is the pathophysiology of Huntington’s disease?

Answer 7

Accumulation of mutant Huntingtin protein
Neurodegeneration in the basal ganglia (progressive degeneration of striatal projection neurones)
Very large expansion of lateral ventricles

Question 8

What are the motor symptoms of HD?

Answer 8

Involuntary movements (chorea) - cannot suppress unwanted motor acts

Question 9

Does neurodegeneration in the basal ganglia in HD happen first in the direct or indirect pathway?

Answer 9

Earliest change in the indirect pathway (contains Enkephalin), later occurs in the direct pathway (contains Substance P)

Question 10

What is the genetic basis (cause) of HD?

Answer 10

Expansion of CAG repeats in HT15 (Huntingtin) gene
Autosomal dominant inheritance
Association between number of CAG repeats & disease severity / onset

Question 11

What is the genetic basis (cause) of HD?

Answer 11

Huntingtin gene mutation (IT15)
Autosomal dominant inheritance
Association between CAG repeats & disease severity / onset

Question 12

We all have different numbers of polymorphic CAG repeats within exon 1, coding for glutamine (Q).

What is the normal, preclinical and HD number of CAG repeats?

Answer 12

• CAG <34: normal range
• CAG 34-39: preclinical
• CAG 40<: HD
• Juvenile onset HD - CAG >60-70