Parkinson’s Plus Disorders:MSA and Related Conditions Flashcards Preview

NMH: Module 2 > Parkinson’s Plus Disorders:MSA and Related Conditions > Flashcards

Flashcards in Parkinson’s Plus Disorders:MSA and Related Conditions Deck (20)
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1

List some cases of parkinsonism

Multiple system atrophy
Progressive supranuclear palsy
Corticobasal degeneration

Idiopathic PD
Drug-induced PD
Vascular pseudo-parkinsonism

2

What is Multiple system atrophy (MSA)?

a-synucleinopathy

Covers 3 disorders:

- olivopontocerebella atrophy (OPCA)
- Shy-Drager syndrome
- Striatonigral degeneration

3

How to categorise MSA?

MSA-P: predominant parkinsonism

MSA-C: cerebellar features

4

Macroscopic pathology of MSA?

- cortical atrophy
- cerebellar atrophy
- shrinkage of middle cerebella peduncle, pons and inferior olive
- pallor of locus coeruleus and substantia nigra

5

Microscopic pathology of MSA?

- oligo inclusions of a-syn {Papp-Lantos bodies)
- mixed neuronal & glial pathology
- a-synuclein immunoreactive glial cytoplasmic inclusions (GCI)
- neuronal cytoplasmic inclusions, neuronal nuclear inclusions, glial nuclear inclusions and neuropil threads

6

Clinical features of corticobasal degeneration (CBD)?

Rigidity, clumsiness, stiffness, arm jerking, "alien limb"

7

Affected sites in CBD?

Cerebral cortex (fronto-parietal atrophy)
Deep cerebellar nuclei
Substantia nigra

8

Histological features of CBD

Neuronal and glial inclusions

Neuropil threads

Balloon neurons and astrocytic plaques

9

Clinical features of Progressive Supranuclear Palsy (PSP)?

Supranuclear gaze palsy & postural instability

10

Affected sites in PSP?

Atrophy of:
- basal ganglia
- subthalamus
- brainstem

11

Histological features of PSP?

Neuronal loss and gliosis

Neuronal and glial tau-positive inclusions

Tufted astrocytes and coiled bodies (in oligodendrocytes)

12

Chromosomal location of tau and number of exons?

Single gene on 17q21

16 exons

13

Isoforms of tau?

6 isoforms

3R or 4R -tau (microtubule-binding domains)

2 further inserts w/ unknown function
(0N,1N,2N)

[shortest form 3R/0N foetal]

14

Function of tau?

Binds and stabilises microtubules

Promotes microtubule polymerisation

4R-tau more efficient

[other MAPS (microtubule associated proteins) have similar functions]

15

Role of phosphorylation in tau?

Tau function is phosphorylation dependent (79 potential serine/threonine sites)

Clustered around MT binding sites

Increased phosphorylation reduces MT binding

Balance between kinases (GSK 3beta and CDK 5) and phosphatases

16

Specific proteinopathy in MSA, CBD and PSP

MSA: a-synucleinopathy
CBD: tauopathy
PSP: tauopathy

17

How to distinguish Parkinson's plus disorders whilst the pt is still alive?

Biomarkers (although a single protein in CSF cannot define a disease) -> need algorithm to assess many different proteins

MSA has increased a-syn in CSF in PM (distinguishing it from other a-synopathies)

CSF neurofilament levels can indicate signs of CNS damage

18

Using imagine to distinguish Parkinson's plus disorders?

PET can distinguish PSP from CBD, MSA-P and PD

19

Effects of tau knockout?

No phenotype (other MAPs compensate)

20

Western blot: Pathological correlations of tau?

Normal: 6 soluble bands


Alzheimer's: all 6 isoforms involved w/ pathology
Pick's disease: 3R tauopathy
CBD/PSP: 4R tauopathy
FTLD-17 (N296N mutation): 3R tauopathy
FTLD-17 (P301L mutation): 4R tauopathy