Neuropathology 2 Flashcards
examples of primary demyelination?
MS
acute disseminated encephalomyelitis
acute haemorrhagic leukoencephalitis
examples of secondary demyelination?
viral (e.g PML)
metabolic (central pontinemyelinosis)
toxic (CO, organic solvents, cyanide)
demyelination in CNS vs PNS?
oligodendrocytes have limited ability to regenerate (remyelinate axons)
therefore demyelination in CNS is generally permanent and causes more problems than in PNS
what is MS?
autoimmune demyelinating disorder characterized by distinct episodes of neurological deficits seprated in time and which correspond to spatially separated foci of neurological injury
how is MS diagnosed?
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
clinical features of MS affecting optic nerve?
optic neuritis - visual unilateral impairment
features of MS affecting spinal cord?
motor or sensory deficit in trunk and limbs
spasticity
bladder dysfunction
features of MS affecting brain stem?
cranial nerve signs
ataxia
nystagmus
internuclear opthalmoplegia
morphology of MS?
white matter disease
exterior surface appears normal but cut surface shows plaques
what are plaques?
well circumsized, well demarcated irregularly shaped areas
have a glassy, almost translucent appearance
can be very small - very large
non-anatomical distribution
locations frequenctly affected by plaques?
beside lateral ventrcles corpus callosum optic nerve/chiasm brainstem ascending/descending tracts cerebellum spinal cord
describe active plaques?
perivascular inflammatory cells
microglia
ongoing demyelination
yellow/brown appearance with ill defined edge
describe inactive plaques?
gliosis
little remaining myelinated axons
oligodendrocytes and axons reduced in number
grey/brown in appearance with well defined edge, usually found around lateral ventricles
shadow plaques?
may reflect degree of remyelination
results in a less well defined lesion
environmental factors on MS development?
latitude
Vit D deficiency
possible viral trigger (EBV)
in which ways is MS an immune mediated disease?
lymphatic infiltration on histology
oligoclonal IgG bands in CSF
genetic linkage to HLA DRB1
most neurodegenerative diseases are a process of what?
simple neuronal atrophy and subsequent gliosis
degeneration at which sites causes which diseases?
cerebral cortex = alzheimers, pick, CJD
basal ganglia - parkinsons, huntingtons
spinocerebellar (apinocerebellar ataxia)
motor neurones (MND)
what is dementia?
acquired and persistent generalised disturbance of higher mental function in an otherwise fully alert person
classification of dementia?
primary (occur on their own - alzheimers, lewy nody, picks disease, huntingtons)
secondary (as a result of something else - multi-infarct (vascular), infection, trauma, metabolic)
most common cause of dementia in elderly?
alzheimers disease
who is alzhimers most common in?
females
over 85s
can be familial in some (amyloid precursor protein, presenilin 1 and 2)
increased incidence in trisomy 21 (APP)
what happens in alzheimers?
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
what causes death in alzheimers?
usually due to secondary causes like pneumonia
alzheimers macroscopic pathology?
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)
microscopic features of alzheimers?
neuronal loss with astrocyte proliferation (neuronal atrophy and gliosis)
neurofibrillary tangles
neuritic plaques (ABeta amyloid plaques, surrounding astrocytes and microglia)
what are neurofibrillary tangles?
intracytoplasmic aggregates of tau protein associated with microtubules
seen mainly in hippocampus and temporal lobe
what is A beta amyloid?
produced by cleavage of amyloid precursor protein (APP)
central element of neuritic plaques
why does down syndrome cause early alzheimers?
APP is on chromosome 21
features of amyloid angiopathy in the brain?
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
features of lewy body dementia?
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
examples of parkinsonism features?
loss of facial expression, stooping, shuffling gait, slow initiation of movement, stiffness and pill rolling tremor
what is seen in the brain in lewy body dementia?
degeneration of substantia nigra (as in parkinsons disease)
pallor in substantia nigra where pigmented dopaminergic neurones usually run
microscopic features of lewy body dementia?
loss of pigmented neurons
reactive gliosis, microglial accumulation
remaining neurons show lewy bodies
fewer cortical lewy bodies
what are lewy bodies?
intracytoplasmic aggregates of alpha synuclein and ubiquitin protein
features of huntingtons?
triad of emotional, cognitive and motor disturbance
chorea, myoclonus, clumsiness, slurred speech, depression, irritability and apathy
develop dementia later but insight remains intact
genetics of huntingtons?
AD inheritance
mutant gene with over 35 repeats of CAG codon
macroscopic features of huntingtons?
atrophy of basal ganglia - caudate nucleus and putamen
cortical atrophy occurs later (dementia onset)
microscopic features of huntingtons?
single neuronal atrophy of striatal neurones in basal ganglia
pronounced astrocytic gliosis
microscopic features of huntingtons?
single neuronal atrophy of striatal neurones in basal ganglia
pronounced astrocytic gliosis
describe features of picks disease (fronto-temporal dementia)?
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)
what is seen in the brain in fronto-temporal dementia?
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
what is vascular dementia?
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
you need to loose how much brain tissue before vascular dementia occurs?
50-100ml
not much to do with where infarct occurs, but more how much brain volume is lost
describe multi-infarct (vascular) dementia?
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
clues to differentiate vascular from alzheimers?
abrupt onset
stepwise progression rather than progressive decline
cardiovascular history
evidence of stroke on CT or MRI
most common morphological appearance of vascular dementia?
large vessel infarcts scattered throughout hemispheres
atheroma of large cerebral arteries provoke thromboembolism
less common morphological appearance of vascular dementia?
small vessel (lacunar) infarcts central, subcortical distribution particularly related to longstanding hypertension and arteriosclerosis of small vessels
