Neurodegeneration

Question 1

What is the difference between
1. Kreuzfeld Jacob diesease
2. Gerstman-Straüsseler-Sheinker syndrome
3. Kuru
4. Ftatal Familial insomnia

Answer 1

All are proteinopathy causing spongiform changes in brain

1. Kreuzfeld Jacob : injestion/ infection with prion protein (can be spontaneous or aquired with different causeses)
2. Gerstman-Straüssler-Sheinker: genetic variation leading to change in protein (genetic cause of prion disease)
3. Kuru CJD due to cannibalism
4. Fatal Familial insomnia Genetic form of prion diesease

Question 2

What is alzheimers disease?

What is the epidemiology?

Answer 2

Commonest cause of dementia

Usually >50, increasing incidence wih age

Question 3

What are the pathophysiological changes in alzheimers diseae?

Answer 3

Different plaques lead to
1. Senile** Extracellular plaques** (due to changes in cleavage of amyloid protein) –> Neurotoxic effect and n**euronal loss (cerebral atrophy) **
2. Neurofibrillary tangles (due to abnormal, hyperphosphorylated TAU protein)
3. Reduced cholinergic function (due to loss of neurons)

Question 4

How can Alzheimers dieseae be diagnosed?

Answer 4

Usually clinical diagnosis with aid of neuroimaging

but definitive diagnosis on post-mortem pathology

Question 5

What are the histological changes seen in alzheimers disease?

Answer 5

1. beta - Amyloid plaques (including cerebral amyloid angiopathy –> depsition of bea amyloid in vascular walls) (picture)
   2.Neurofibrillary tangles of tau protein

Question 6

How is alzheimers disease stages post-mortem?

Answer 6

Braak staging
Based on amount and location of Tau protein

Question 7

What are radiological changes seen in Alzheimers disease?

Answer 7

General brain atrophy
* widened sulci, narrowed gyri
* enlarged ventricles (most →marked in temporal and frontal lobes with loss of cholinergic neurons)

Question 8

What is the difference beween Parkinsons and Lewy body dementia?

Answer 8

The onset of symptoms, otherwise indistingishable

Lewy body:dementia starts before/ at same time as Parkisonsm

PD: dementia starts >1 year after onset of symptoms

Question 9

What are the histological changes in Parkinson’s disease and Lewy body dementia?

Answer 9

Loss of dopaminergic neurons substantia nigra (right picture)

Lewy bodies in cells

Question 10

What are classical clinical features of Lewy body dementia?

Answer 10

Psychological disturbances occur early
* Day-to-day fluctuations in cognitive performance and alertness
* visual hallucinations (BUZZWORD – little people/animals running around),

+ Motor signs of parkisonism

Question 11

What abnormal protein causes Lewy bodies in parkinson’s disease?

Answer 11

misfolded α-synuclein

Question 12

What areas of the brain are firstly affected by Parkinson’s disease / Lewy body dementia and how does it usually progress?

Answer 12

Usually starts los in brainstem, spreads upwards and into hemisphere

nigrostriatal pathway –> from substantia nigra in basal ganglia to striatum

Question 13

What is Pick’s disease?

What area of the brain is usually affected?

Whar is a typical presentation=

Answer 13

Most common type of frontotemporal dementias due to hyperphosphorylated tau abnormalities (Pick bodies)

This only affects the frontal and temporal lobes → atrophy

Mutations: progranulin gene
There is a strong FHx and often affects younger people (40-60yrs)

Classical symptoms include personality change, disinhibition, overeating, emotional blunting

Question 14

What is the definition of a parkinson plus syndrome?

Answer 14

Syndromes that occur in addition to the core features of parkisonism

(Tremor, Rigiditiy, Akinesia + Postural instabilit)

Question 15

What is Multiple system atrophy?

Answer 15

A parkinsom plus syndrome (therefore also due to Alpha-synuclein protein abnormalities)

usually presenting with early autonomic dysfunction