Degeneration and Dementia

Question 1

What are the different types of neurodegeneration?

Answer 1

Wallerian – distal degeneration of axon and myelin
Axonal – dying back of axon proximal to cell body
Myelin – loss of oligodenrdroglial/schwann cells affecting conduction velocity
Multiple Sclerosis (central)
Guillain Barré (peripheral)

Question 2

What are the common causes of wallerian degeneration and what are its 3 classifications?

Answer 2

Head trauma (DIA/ SBS) / nerve compression
Neuropraxia
Axonotmesis
Neurotmesis

Question 3

What protein related changes would you see in neurodegenerative disorders?

Answer 3

Amyloid plaques
Tau (Neurofibrillary tangles)
Lewy Bodies/Pick cells ((inclusions)
Prion proteins

Question 4

What amyloid plaques are found in Parkinsons and Mad cow disease?

Answer 4

PD - alpha-synuclein

CJD - Prion

Question 5

What are inclusions?

Answer 5

Intracellular protein aggregaations - lewy bodies/pick cells
alpha-synuclein
ubiquitin
crystallin
neurofilament

Question 6

What are prion proteins?

Answer 6

proteinaceous infectious particle
presynaptic transport and cell signalling
β–sheets and fibrils
Visible amyloid plaques and vacuolisation giving spongiform appearance

Question 7

What are examples of peripheral and central degenerative disorders?

Answer 7

Peripheral:
Diabetic Neuropathy
Motorneuron disease (MND)
Amylotrophic Lateral Sclerosis
Guillain Barré syndrome
Central:
Multiple Sclerosis
Alzheimer’s
Parkinson’s
Huntington’s

Question 8

What causes motor neuron disease?

Answer 8

degeneration of the motor pathways, affecting outflow from the anterior horn cells

Question 9

What causes amylotrophic lateral sclerosis?

Answer 9

Changes in SOD1 gene lead to protein misfolding, reduced ROS (reactive oxygen species) removal
Loss of motor neurons - at the level of the corticospinal tract (Betz cells) and anterior horn cell. Thinning of anterior roots and fibre pathways.

Question 10

What causes Guillain-Barré syndrome?

Answer 10

Cause unknown, autoimmune reaction triggered by preceding viral/bacterial infection

Question 11

What are the symptoms of Guillain-Barré syndrome?

Answer 11

Rapid onset weakness and tingling that spreads through body
Normally starts in feet/legs and spreads upwards
Peak symptoms occur approx. 2-4 weeks after onset
Can lead to paralysis

Question 12

What is multiple sclerosis? what causes it? what are the symptoms?

Answer 12

Primary inflammatory, autoimmune disease causing CNS demyelination
Diff patterns of disease - relapsing remitting most likely
Optic neuritis
weakness
numbness

Question 13

In a CSF sample, if you found oligoclonal (immunoglobin) bands, what does that indicate?

Answer 13

Multiple Sclerosis

Question 14

What pathological proteins are found in parkinsons? and where?

Answer 14

Alpha Synuclein - substantia nigra par compacta

Question 15

What are the symptoms of parkinsons? (TRAP)

Answer 15

Tremors
Rigidity
Akinesia
Postural instability

Question 16

How can you truly diagnose parkinsons?

Answer 16

Post-mortem biopsy:
Loss of DA neurons in SN
Presence of Lewy Bodies
Raised α-synuclein/parkin levels

Question 17

What are the causes of huntingtons disease?

Answer 17

Genetic – autosomal dominant
Loss of GABA neurons
Loss of cholinergic function (Ach)
Astrocytosis (inc)
Loss of Substance P

Question 18

In imaging, if you see a Shrunken caudate head and Ex vacuo dilatation, what can you diagnose?

Answer 18

Huntingtons

Question 19

What are the causes of Spongiform encephalopathies/

Creutzfeld-Jakob disease?

Answer 19

Prion protein alteration from PrPc to PrPsc
Genetic
Transmissable

Question 20

What are examples of acute, subacute and chronic diseases?

Answer 20

Acute (weeks) - encephalitis
Subacute (months) - CJD
Chronic (years) - Alz, normal pressure hydrocephalus

Question 21

What is the gross morphology of Alzheimer’s? That you can confirm with.

Answer 21

Cerebral atrophy - hippocampal/temporal/cortical

Question 22

What is the most common type of dementia?

Answer 22

1st - AD
2nd - Vascular dementia (stroke related)
3rd - Dementia with lewy bodies (DLB)
4th - Fronto-temporal dementia

Question 23

What are the protein deposits in DLB?

Answer 23

alpha-synuclein

Dopamine and Acetycholine neurons lost

Question 24

How can you image a DLB?

Answer 24

DaTSCAN - may show reduced striatal DAT binding in DLB patients

Question 25

What are the 3 cardinal features of normal pressure hydrocephalus? How can it be detected on imaging?

Answer 25

Gait disturbance
Cognitive decline – subcortical pattern
Urinary incontinence
Characterised by ventriculomegaly on imaging