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Neurology > Neuropathology 2 > Flashcards

Neuropathology 2 Flashcards

1
Q

examples of primary demyelination?

A

MS
acute disseminated encephalomyelitis
acute haemorrhagic leukoencephalitis

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2
Q

examples of secondary demyelination?

A

viral (e.g PML)
metabolic (central pontinemyelinosis)
toxic (CO, organic solvents, cyanide)

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3
Q

demyelination in CNS vs PNS?

A

oligodendrocytes have limited ability to regenerate (remyelinate axons)
therefore demyelination in CNS is generally permanent and causes more problems than in PNS

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4
Q

what is MS?

A

autoimmune demyelinating disorder characterized by distinct episodes of neurological deficits seprated in time and which correspond to spatially separated foci of neurological injury

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5
Q

how is MS diagnosed?

A 
two distinct neurological defects occurring at different times
neurological deficit implicating one neuro-anatomical site and in MRI appreciated defect at another neuro-anatomical site
multiple distinct (usually white matter) CNS lesions on MRI
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6
Q

clinical features of MS affecting optic nerve?

A

optic neuritis - visual unilateral impairment

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7
Q

features of MS affecting spinal cord?

A

motor or sensory deficit in trunk and limbs
spasticity
bladder dysfunction

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8
Q

features of MS affecting brain stem?

A

cranial nerve signs
ataxia
nystagmus
internuclear opthalmoplegia

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9
Q

morphology of MS?

A

white matter disease

exterior surface appears normal but cut surface shows plaques

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10
Q

what are plaques?

A

well circumsized, well demarcated irregularly shaped areas
have a glassy, almost translucent appearance
can be very small - very large
non-anatomical distribution

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11
Q

locations frequenctly affected by plaques?

A 
beside lateral ventrcles
corpus callosum
optic nerve/chiasm
brainstem
ascending/descending tracts
cerebellum
spinal cord
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12
Q

describe active plaques?

A

perivascular inflammatory cells
microglia
ongoing demyelination
yellow/brown appearance with ill defined edge

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13
Q

describe inactive plaques?

A

gliosis
little remaining myelinated axons
oligodendrocytes and axons reduced in number
grey/brown in appearance with well defined edge, usually found around lateral ventricles

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14
Q

shadow plaques?

A

may reflect degree of remyelination

results in a less well defined lesion

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15
Q

environmental factors on MS development?

A

latitude
Vit D deficiency
possible viral trigger (EBV)

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16
Q

in which ways is MS an immune mediated disease?

A

lymphatic infiltration on histology
oligoclonal IgG bands in CSF
genetic linkage to HLA DRB1

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17
Q

most neurodegenerative diseases are a process of what?

A

simple neuronal atrophy and subsequent gliosis

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18
Q

degeneration at which sites causes which diseases?

A

cerebral cortex = alzheimers, pick, CJD
basal ganglia - parkinsons, huntingtons
spinocerebellar (apinocerebellar ataxia)
motor neurones (MND)

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19
Q

what is dementia?

A

acquired and persistent generalised disturbance of higher mental function in an otherwise fully alert person

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20
Q

classification of dementia?

A

primary (occur on their own - alzheimers, lewy nody, picks disease, huntingtons)
secondary (as a result of something else - multi-infarct (vascular), infection, trauma, metabolic)

21
Q

most common cause of dementia in elderly?

A

alzheimers disease

22
Q

who is alzhimers most common in?

A

females
over 85s
can be familial in some (amyloid precursor protein, presenilin 1 and 2)
increased incidence in trisomy 21 (APP)

23
Q

what happens in alzheimers?

A

insidious impairment of higher intellectual function with alteration in mood and behaviour
later = progressive disorientation, memory loss and aphasia
can result in profound disability, muteness and immobility

24
Q

what causes death in alzheimers?

A

usually due to secondary causes like pneumonia

25
Q

alzheimers macroscopic pathology?

A

decreased size and weight of brain (cortical atrophy)
widening of sulci and narrowing of gyri
compensatory dilation of ventricles causing a hydrocephalus
occipital lobe spared
normal brainstem and cerebellum
can spare certain areas (e.g occipital lobes are normal - normal vision etc)

26
Q

microscopic features of alzheimers?

A

neuronal loss with astrocyte proliferation (neuronal atrophy and gliosis)
neurofibrillary tangles
neuritic plaques (ABeta amyloid plaques, surrounding astrocytes and microglia)

27
Q

what are neurofibrillary tangles?

A

intracytoplasmic aggregates of tau protein associated with microtubules
seen mainly in hippocampus and temporal lobe

28
Q

what is A beta amyloid?

A

produced by cleavage of amyloid precursor protein (APP)

central element of neuritic plaques

29
Q

why does down syndrome cause early alzheimers?

A

APP is on chromosome 21

30
Q

features of amyloid angiopathy in the brain?

A

extracellular eosinophilic accumulation
polymerised beta pleated sheets formed by ABeta
stains with congo red
disrupts blood brain barrier leading to serum leaking, oedema and local hypoxia

31
Q

features of lewy body dementia?

A

progressive dementia along with hallucinations and fluctuating levels of attention/cognition
fluctuation in severity of condition on a day to day basis
often have features of parkinsonism at onset or shortly after

32
Q

examples of parkinsonism features?

A

loss of facial expression, stooping, shuffling gait, slow initiation of movement, stiffness and pill rolling tremor

33
Q

what is seen in the brain in lewy body dementia?

A

degeneration of substantia nigra (as in parkinsons disease)

pallor in substantia nigra where pigmented dopaminergic neurones usually run

34
Q

microscopic features of lewy body dementia?

A

loss of pigmented neurons
reactive gliosis, microglial accumulation
remaining neurons show lewy bodies
fewer cortical lewy bodies

35
Q

what are lewy bodies?

A

intracytoplasmic aggregates of alpha synuclein and ubiquitin protein

36
Q

features of huntingtons?

A

triad of emotional, cognitive and motor disturbance
chorea, myoclonus, clumsiness, slurred speech, depression, irritability and apathy
develop dementia later but insight remains intact

37
Q

genetics of huntingtons?

A

AD inheritance

mutant gene with over 35 repeats of CAG codon

38
Q

macroscopic features of huntingtons?

A

atrophy of basal ganglia - caudate nucleus and putamen

cortical atrophy occurs later (dementia onset)

39
Q

microscopic features of huntingtons?

A

single neuronal atrophy of striatal neurones in basal ganglia
pronounced astrocytic gliosis

40
Q

microscopic features of huntingtons?

A

single neuronal atrophy of striatal neurones in basal ganglia
pronounced astrocytic gliosis

41
Q

describe features of picks disease (fronto-temporal dementia)?

A 
personality and behavioural changes
speech and communication problems
changes in eating habits
reduced attention span
usually begins in middle age
lasts between 2-10 years (usually around 7)
42
Q

what is seen in the brain in fronto-temporal dementia?

A

extreme atrophy of cerebral cortex in frontal and later temporal lobes
brain weighs <1kg
neuronal loss and gliosis
picks cells (swollen neurones)
intracytoplasmic filamentous inclusions known as picks bodies

43
Q

what is vascular dementia?

A

disorder involving a deterioration in mental functioning due to cumulative damage to the brain via hypoxia or anoxia as a result of multiple blood clots

44
Q

you need to loose how much brain tissue before vascular dementia occurs?

A

50-100ml

not much to do with where infarct occurs, but more how much brain volume is lost

45
Q

describe multi-infarct (vascular) dementia?

A

successive, multi-infarct cerebral infarctions cause increasingly larger areas of cell death and damage
when enough of brain is damaged, dementia results
sufferers aware of mental deficits and are prone to depression and anxiety

46
Q

clues to differentiate vascular from alzheimers?

A

abrupt onset
stepwise progression rather than progressive decline
cardiovascular history
evidence of stroke on CT or MRI

47
Q

most common morphological appearance of vascular dementia?

A

large vessel infarcts scattered throughout hemispheres

atheroma of large cerebral arteries provoke thromboembolism

48
Q

less common morphological appearance of vascular dementia?

A 
small vessel (lacunar) infarcts
central, subcortical distribution
particularly related to longstanding hypertension and arteriosclerosis of small vessels

Neurology (53 decks)

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