Demyelination & Dementia

Question 1

what 2 structures are damaged during the process of demyelination?

Answer 1

myelin sheath itself

oligodendrocytes / schwann cells which form myelin sheaths

Question 2

what is the primary demyelinating disease process in adults?

Answer 2

MS

Question 3

what primary demyelinating diseases are more common in children?

Answer 3

acute disseminated encephalomyelitis (self limiting)

acute haemorrhagic leukoencephalitis (rapidly fatal)

Question 4

what are secondary causes of demyelination?

Answer 4

viral eg progressive multifocal leukoencephalopathy (PML)

metabolic eg central pontine myelinosis

toxic agents eg carbon monoxide

Question 5

why does MS present as hyperintense lesions in the white matter on MRI?

Answer 5

most axons are concentrated in the white matter

Question 6

what CSF sign is indicative of MS?

Answer 6

IgG oligoclonal bands in CSF

Question 7

what focal neurological signs do patients with MS present if they have optic nerve lesions?

Answer 7

optic neuritis - unilateral visual impairment

Question 8

what focal neurological signs do MS patients present with if they have lesions in spinal cord?

Answer 8

motor or sensory deficit in trunk and limbs
spasticity
bladder dysfunction

Question 9

what focal neurological signs are present in MS patients with brainstem lesions?

Answer 9

cranial nerve signs
ataxia
nystagmus
internuclear ophthalmoplegia

Question 10

describe the appearance of plaques in MS?

Answer 10

well circumscribed 
irregular shaped 
glassy / translucent experience
vary in size 
non-anatomical distribution

Question 11

what areas of the brain are plaques normally found in?

Answer 11

adjacent to lateral ventricles 
corpus callosum 
optic nerves 
brainstem 
cerebellum

Question 12

explain the histological findings in an acute active MS lesion?

Answer 12

microglia (digest myelin like macrophage)
inflammatory cells around blood vessels
plaques grow in a perivascular distribution

Question 13

describe the histological findings in a chronic or inactive MS lesion?

Answer 13

gliosis (proliferation of glial cells)

less oligodendrocytes and myelinated axons present

Question 14

what is the difference in the macroscopic appearance of active and inactive MS lesions?

Answer 14

active = ill defined edge

inactive = well demarcated

Question 15

give examples of degenerative diseases of the cerebral cortex?

Answer 15

alzheimer’s disease

CJD

Question 16

what neurodegenerative diseases originate in the basal ganglia and brainstem?

Answer 16

parkinson disease
progressive supranuclear palsy
huntington disease

Question 17

where else can neurodegenerative disease present aside from the cerebral cortex, brainstem and basal ganglia?

Answer 17

cerebellum (freidrich’s ataxia)

motor neurones (MND)

Question 18

dementia is an ageing process and not pathological - true or false?

Answer 18

false

dementia is not part of the normal ageing process

Question 19

give examples of primary dementia?

Answer 19

alzheimer’s disease

lewy body dementia

Question 20

give examples of causes of secondary dementia?

Answer 20

multi infarct (vascular) dementia
infection (HIV, syphillis)
trauma
metabolic

Question 21

what symptoms can alzheimers progress to show in the later stages?

Answer 21

disorientation
worsened memory loss
aphasia
profound disability/immobility

Question 22

patients with alzheimers usually die of the disease - true or false?

Answer 22

false

death usually occurs due to secondary cause ie bronchopneumonia

Question 23

describe the macroscopic appearance of the brain in alzheimers dementia?

Answer 23

cortical atrophy in frontal, temporal and parietal lobes (occipital, brainstem and cerebellum spared)

widening of sulci / narrowing of gyri

dilation of ventricles

Question 24

what microscopic features are typical of alzheimers disease?

Answer 24

neuronal loss (+ astrocyte proliferation = gliosis)

neurofibrillary tangles (in hippocampus and temporal lobe)

neuritic plaques due to amyloid angiopathy

Question 25

why is alzheimers disease thought to be more common in those with down syndrome (trisomy 21)?

Answer 25

genetically have more of amyloid protein precursor (on chromosome 21) = more at risk of amyloid angiopathy

Question 26

describe the microscopic appearance of amyloid angiopathy?

Answer 26

extracellular eosinophils polymerised beta pleated sheats stains with congo red disrupts BBB - local oedema

Question 27

what is lewy body dementia?

Answer 27

``` progressive dementia hallucinations fluctuating levels of attention / cognition fluctuation on day to day basis features of parkinsonism ```

Question 28

what are the clinical features of parkinsons disease?

Answer 28

``` loss of facial expression stooping shuffling gait slow initiation of movements stiffness pill rolling tremor ```

Question 29

where in the brain does lewy body dementia cause degeneration?

Answer 29

in the substantia nigra (similar to parkinsons)

Question 30

describe how lewy body dementia appears microscopically?

Answer 30

loss of pigmented neurones reactive gliosis remaining neurones may show lewy bodies

Question 31

when are patients with huntingtons disease usually diagnosed and when does dementia develop?

Answer 31

usually diagnosed between 35-50 | dementia presents later in disease process

Question 32

how does huntington's dementia appear macroscopically in brain?

Answer 32

atrophy of basal ganglia - caudate nucleus and putamen cortical atrophy occurs later

Question 33

how does huntingtons disease appear microscopically in the brain?

Answer 33

atrophy of striatal neurones in basal ganglia | astrocytic gliosis

Question 34

what condition is responsible for fronto-temporal dementia??

Answer 34

pick's disease

Question 35

when does pick's disease usually present?

Answer 35

commencing in middle life (usually between 50 and 60 years)

Question 36

what symptoms do patients with pick's disease get (relating to damage of frontal / temporal lobes)?

Answer 36

personality and behavioural change speech and communication problems changes in eating habits reduced attention span

Question 37

picks disease is naturally progressive - how many years do patients normally live with this?

Answer 37

2-10 years (average = 7)

Question 38

how does pick's disease appear macroscopically?

Answer 38

extreme atrophy of cerebral cortex in frontal and later in temporal lobes brain weight <1kg

Question 39

how does pick's disease appear microscopically and what are hallmarks of disease?

Answer 39

neuronal loss and gliosis hallmarks - picks cells (swollen neurones), intracytoplasmic filamentous inclusions (picks bodies)

Question 40

what groups of patients are most likely to get multi infarct dementia?

Answer 40

men > women | >60 most common but also seen in middle aged hypertensives

Question 41

what clues can help to distinguish multi-infarct dementia from alzheimers disease?

Answer 41

abrupt onset stepwise progression history or hypertension / stroke evidence of stroke on CT / MRI