Demyelination & Dementia Flashcards
what 2 structures are damaged during the process of demyelination?
myelin sheath itself
oligodendrocytes / schwann cells which form myelin sheaths
what is the primary demyelinating disease process in adults?
MS
what primary demyelinating diseases are more common in children?
acute disseminated encephalomyelitis (self limiting)
acute haemorrhagic leukoencephalitis (rapidly fatal)
what are secondary causes of demyelination?
viral eg progressive multifocal leukoencephalopathy (PML)
metabolic eg central pontine myelinosis
toxic agents eg carbon monoxide
why does MS present as hyperintense lesions in the white matter on MRI?
most axons are concentrated in the white matter
what CSF sign is indicative of MS?
IgG oligoclonal bands in CSF
what focal neurological signs do patients with MS present if they have optic nerve lesions?
optic neuritis - unilateral visual impairment
what focal neurological signs do MS patients present with if they have lesions in spinal cord?
motor or sensory deficit in trunk and limbs
spasticity
bladder dysfunction
what focal neurological signs are present in MS patients with brainstem lesions?
cranial nerve signs
ataxia
nystagmus
internuclear ophthalmoplegia
describe the appearance of plaques in MS?
well circumscribed irregular shaped glassy / translucent experience vary in size non-anatomical distribution
what areas of the brain are plaques normally found in?
adjacent to lateral ventricles corpus callosum optic nerves brainstem cerebellum
explain the histological findings in an acute active MS lesion?
microglia (digest myelin like macrophage)
inflammatory cells around blood vessels
plaques grow in a perivascular distribution
describe the histological findings in a chronic or inactive MS lesion?
gliosis (proliferation of glial cells)
less oligodendrocytes and myelinated axons present
what is the difference in the macroscopic appearance of active and inactive MS lesions?
active = ill defined edge
inactive = well demarcated
give examples of degenerative diseases of the cerebral cortex?
alzheimer’s disease
CJD
what neurodegenerative diseases originate in the basal ganglia and brainstem?
parkinson disease
progressive supranuclear palsy
huntington disease
where else can neurodegenerative disease present aside from the cerebral cortex, brainstem and basal ganglia?
cerebellum (freidrich’s ataxia)
motor neurones (MND)
dementia is an ageing process and not pathological - true or false?
false
dementia is not part of the normal ageing process
give examples of primary dementia?
alzheimer’s disease
lewy body dementia
give examples of causes of secondary dementia?
multi infarct (vascular) dementia
infection (HIV, syphillis)
trauma
metabolic
what symptoms can alzheimers progress to show in the later stages?
disorientation
worsened memory loss
aphasia
profound disability/immobility
patients with alzheimers usually die of the disease - true or false?
false
death usually occurs due to secondary cause ie bronchopneumonia
describe the macroscopic appearance of the brain in alzheimers dementia?
cortical atrophy in frontal, temporal and parietal lobes (occipital, brainstem and cerebellum spared)
widening of sulci / narrowing of gyri
dilation of ventricles
what microscopic features are typical of alzheimers disease?
neuronal loss (+ astrocyte proliferation = gliosis)
neurofibrillary tangles (in hippocampus and temporal lobe)
neuritic plaques due to amyloid angiopathy
why is alzheimers disease thought to be more common in those with down syndrome (trisomy 21)?
genetically have more of amyloid protein precursor (on chromosome 21) = more at risk of amyloid angiopathy
describe the microscopic appearance of amyloid angiopathy?
extracellular eosinophils
polymerised beta pleated sheats
stains with congo red
disrupts BBB - local oedema
what is lewy body dementia?
progressive dementia hallucinations fluctuating levels of attention / cognition fluctuation on day to day basis features of parkinsonism
what are the clinical features of parkinsons disease?
loss of facial expression stooping shuffling gait slow initiation of movements stiffness pill rolling tremor
where in the brain does lewy body dementia cause degeneration?
in the substantia nigra (similar to parkinsons)
describe how lewy body dementia appears microscopically?
loss of pigmented neurones
reactive gliosis
remaining neurones may show lewy bodies
when are patients with huntingtons disease usually diagnosed and when does dementia develop?
usually diagnosed between 35-50
dementia presents later in disease process
how does huntington’s dementia appear macroscopically in brain?
atrophy of basal ganglia - caudate nucleus and putamen
cortical atrophy occurs later
how does huntingtons disease appear microscopically in the brain?
atrophy of striatal neurones in basal ganglia
astrocytic gliosis
what condition is responsible for fronto-temporal dementia??
pick’s disease
when does pick’s disease usually present?
commencing in middle life (usually between 50 and 60 years)
what symptoms do patients with pick’s disease get (relating to damage of frontal / temporal lobes)?
personality and behavioural change
speech and communication problems
changes in eating habits
reduced attention span
picks disease is naturally progressive - how many years do patients normally live with this?
2-10 years (average = 7)
how does pick’s disease appear macroscopically?
extreme atrophy of cerebral cortex in frontal and later in temporal lobes
brain weight <1kg
how does pick’s disease appear microscopically and what are hallmarks of disease?
neuronal loss and gliosis
hallmarks - picks cells (swollen neurones), intracytoplasmic filamentous inclusions (picks bodies)
what groups of patients are most likely to get multi infarct dementia?
men > women
>60 most common but also seen in middle aged hypertensives
what clues can help to distinguish multi-infarct dementia from alzheimers disease?
abrupt onset
stepwise progression
history or hypertension / stroke
evidence of stroke on CT / MRI
