Pathology of Parkinson’s Disease & Atypical Parkinson’s Disease Flashcards
What are examples of dopaminergic nigro-striatal pathway disruption?
- Vascular
- Drug-induced
- Toxic
- Inflammatory
What are the large group due to misfolded protein accumulation?
- Idiopathic PD
- PSP
- CBD
- MSA
What are examples of small proportion that has a known genetic cause?
- Familial PD
- HD
- Wilson disease
- MAPT
What happens to a section from the midbrain?
there is black substance, the substantia nigra - it has disappeared with people with Parkinson’s disease
What is the discovery timeline for Parkinson’s disease?
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
Where do the Braak stages start?
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
What is the typical pathology of Parkinson’s disease?
- 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
Deviation from Braak stage
• 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
Atypical distribution of Lewy body pathology:
- It is not following Braak stage from 1-6
- It is not amygdala dominant
- It has midbrain and frontal cortex involvement
Clinical-pathological correlation in PD:
- 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
Pathological: radiological correlation of MSA
- 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]
Increased likelihood of MSA if development of:
- Autonomic dysfunction within the first 3 years of symptom onset
- Severe orthostatic hypotension
- Urinary incontinence with requirement of urinary catheter
Tauopathies
Tauopathies can be either 3-repeat Tau or 4-repeat Tau or a mixture of 3-repeat and 4-repeat Tau
How are Tauopathies differentiated?
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
Where is Tauopathies described in?
oligodendroglia cells
What are examples with relation to Parkinsonism?
- CorticoBasal Degeneration, CBD
- Progressive Supranuclear Palsy, PSP
Features of PSP
- 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
Pathological -radiological correlation of PSP:
• There are two signs
- Hummingbird sign – midbrain region
- Midbrain tegmentum atrophy
- Mickey mouse sign – midbrain on a different plane
Corticobasal syndrome: clinical diagnosis
Corticobasal degeneration cannot be diagnosed purely on macroscopic examination
Hallmark pathology: Astrocytic plaque, 4R tau
What is strongly associated with downward gaze palsy?
The presence of severe TDP43 pathology in the midbrain tectum
Where is the Tau burden in the olivo-ponto-cerebellar system signifcantly greater in?
TDP43-positive CBD cases
What is less frequent in TDP43- positive cases?
MAPT H1/H1 genotypes
