Pathology of Parkinson’s Disease & Atypical Parkinson’s Disease

Question 1

What are examples of dopaminergic nigro-striatal pathway disruption?

Answer 1

1. Vascular
2. Drug-induced
3. Toxic
4. Inflammatory

Question 2

What are the large group due to misfolded protein accumulation?

Answer 2

1. Idiopathic PD
2. PSP
3. CBD
4. MSA

Question 3

What are examples of small proportion that has a known genetic cause?

Answer 3

• Familial PD
• HD
• Wilson disease
• MAPT

Question 4

What happens to a section from the midbrain?

Answer 4

there is black substance, the substantia nigra - it has disappeared with people with Parkinson’s disease

Question 5

What is the discovery timeline for Parkinson’s disease?

Answer 5

1817 - James Parkinson described Parkinson’s disease?

1865 - William Rutherford Sanders proposed and 1870’s Jean-Martin-Charcot actively introduced the term Parkinson’s disease

Question 6

Where do the Braak stages start?

Answer 6

In the medulla especially in the 10th cranial nerve nuclei
• There is growing evidence that it is coming from the gut – the nerve comes and goes away from the gut
• In the brain, it spreads further to the pons, into the Locus coeruleus
• Spreads further into the substantia nigra – the patient starts to present with parkinsonism
• It spreads further into the hippocampal region – memory becomes impaired
• Spreads further to the various neocortical areas
• It finally affects the sensory cortex in the parietal lobe

Question 7

What is the typical pathology of Parkinson’s disease?

Answer 7

• Black substance disappeared
• Locus Coeruleus have disappeared
• Other important nuclei are putamen, subthalamic nuclei should look normal
• The cerebellar cortex, white matter should look matter

Question 8

Deviation from Braak stage

Answer 8

• There is no strong relationship between density of Lewy body pathology and severity of PD clinical symptoms
- 40% of elderly (85+) individuals have Lewy body pathology
- 67% caudo-rostral pattern
- 32% amygdala-dominant pattern (AD pathology and ApoE4 associated)
• Amygdala-dominant Lewy body pathology is seen in ~40% of AD patients

Question 9

Atypical distribution of Lewy body pathology:

Answer 9

• It is not following Braak stage from 1-6
• It is not amygdala dominant
• It has midbrain and frontal cortex involvement

Question 10

Clinical-pathological correlation in PD:

Answer 10

• Where the disease is motor-predominant, Parkinson’s disease starts quite early
• The patients live quite a long time
• There is another aggressive form – disease starts at an older stage – patients die with the disease much quicker

Question 11

Pathological: radiological correlation of MSA

Answer 11

• In MSA, there is Hot cross bun signs
• Looking at the pons
• Differences in the height of the pontine base
• In histological slice, pattern, the way the pontine base atrophies [transverse fibres atrophied]

Question 12

Increased likelihood of MSA if development of:

Answer 12

1. Autonomic dysfunction within the first 3 years of symptom onset
2. Severe orthostatic hypotension
3. Urinary incontinence with requirement of urinary catheter

Question 13

Tauopathies

Answer 13

Tauopathies can be either 3-repeat Tau or 4-repeat Tau or a mixture of 3-repeat and 4-repeat Tau

Question 14

How are Tauopathies differentiated?

Answer 14

differentiated based where they dominant inclusions is located – the shape of those inclusions either neurons or astrocytes infers different shapes and forms that define what the underlying disease is

Question 15

Where is Tauopathies described in?

Answer 15

oligodendroglia cells

Question 16

What are examples with relation to Parkinsonism?

Answer 16

• CorticoBasal Degeneration, CBD

- Progressive Supranuclear Palsy, PSP

Question 17

Features of PSP

Answer 17

• Substantia nigra atrophy
• Midbrain stands out to look abnormal – the midbrain tegmentum is darker and more discoloured – feature of PSP midbrain tegmentum is atrophied
• The pontine base in PSP is normal
• Thin cerebellar peduncles and atrophied dentate nucleus
• Additional diagnostic hallmark features would be severe atrophy of the subthalamic atrophy

Question 18

Pathological -radiological correlation of PSP:

Answer 18

• There are two signs

• Hummingbird sign – midbrain region
• Midbrain tegmentum atrophy
• Mickey mouse sign – midbrain on a different plane

Question 19

Corticobasal syndrome: clinical diagnosis

Answer 19

Corticobasal degeneration cannot be diagnosed purely on macroscopic examination

Hallmark pathology: Astrocytic plaque, 4R tau

Question 20

What is strongly associated with downward gaze palsy?

Answer 20

The presence of severe TDP43 pathology in the midbrain tectum

Question 21

Where is the Tau burden in the olivo-ponto-cerebellar system signifcantly greater in?

Answer 21

TDP43-positive CBD cases

Question 22

What is less frequent in TDP43- positive cases?

Answer 22

MAPT H1/H1 genotypes