Neuropathology 2

Question 1

examples of primary demyelination?

Answer 1

MS
acute disseminated encephalomyelitis
acute haemorrhagic leukoencephalitis

Question 2

examples of secondary demyelination?

Answer 2

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

Question 3

demyelination in CNS vs PNS?

Answer 3

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

Question 4

what is MS?

Answer 4

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

Question 5

how is MS diagnosed?

Answer 5

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

Question 6

clinical features of MS affecting optic nerve?

Answer 6

optic neuritis - visual unilateral impairment

Question 7

features of MS affecting spinal cord?

Answer 7

motor or sensory deficit in trunk and limbs
spasticity
bladder dysfunction

Question 8

features of MS affecting brain stem?

Answer 8

cranial nerve signs
ataxia
nystagmus
internuclear opthalmoplegia

Question 9

morphology of MS?

Answer 9

white matter disease

exterior surface appears normal but cut surface shows plaques

Question 10

what are plaques?

Answer 10

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

Question 11

locations frequenctly affected by plaques?

Answer 11

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

Question 12

describe active plaques?

Answer 12

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

Question 13

describe inactive plaques?

Answer 13

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

Question 14

shadow plaques?

Answer 14

may reflect degree of remyelination

results in a less well defined lesion

Question 15

environmental factors on MS development?

Answer 15

latitude
Vit D deficiency
possible viral trigger (EBV)

Question 16

in which ways is MS an immune mediated disease?

Answer 16

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

Question 17

most neurodegenerative diseases are a process of what?

Answer 17

simple neuronal atrophy and subsequent gliosis

Question 18

degeneration at which sites causes which diseases?

Answer 18

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

Question 19

what is dementia?

Answer 19

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

Question 20

classification of dementia?

Answer 20

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

Question 21

most common cause of dementia in elderly?

Answer 21

alzheimers disease

Question 22

who is alzhimers most common in?

Answer 22

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

Question 23

what happens in alzheimers?

Answer 23

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

Question 24

what causes death in alzheimers?

Answer 24

usually due to secondary causes like pneumonia

Question 25

alzheimers macroscopic pathology?

Answer 25

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)

Question 26

microscopic features of alzheimers?

Answer 26

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

Question 27

what are neurofibrillary tangles?

Answer 27

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

Question 28

what is A beta amyloid?

Answer 28

produced by cleavage of amyloid precursor protein (APP) | central element of neuritic plaques

Question 29

why does down syndrome cause early alzheimers?

Answer 29

APP is on chromosome 21

Question 30

features of amyloid angiopathy in the brain?

Answer 30

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

Question 31

features of lewy body dementia?

Answer 31

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

Question 32

examples of parkinsonism features?

Answer 32

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

Question 33

what is seen in the brain in lewy body dementia?

Answer 33

degeneration of substantia nigra (as in parkinsons disease) | pallor in substantia nigra where pigmented dopaminergic neurones usually run

Question 34

microscopic features of lewy body dementia?

Answer 34

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

Question 35

what are lewy bodies?

Answer 35

intracytoplasmic aggregates of alpha synuclein and ubiquitin protein

Question 36

features of huntingtons?

Answer 36

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

Question 37

genetics of huntingtons?

Answer 37

AD inheritance | mutant gene with over 35 repeats of CAG codon

Question 38

macroscopic features of huntingtons?

Answer 38

atrophy of basal ganglia - caudate nucleus and putamen | cortical atrophy occurs later (dementia onset)

Question 39

microscopic features of huntingtons?

Answer 39

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

Question 40

microscopic features of huntingtons?

Answer 40

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

Question 41

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

Answer 41

``` 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) ```

Question 42

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

Answer 42

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

Question 43

what is vascular dementia?

Answer 43

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

Question 44

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

Answer 44

50-100ml | not much to do with where infarct occurs, but more how much brain volume is lost

Question 45

describe multi-infarct (vascular) dementia?

Answer 45

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

Question 46

clues to differentiate vascular from alzheimers?

Answer 46

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

Question 47

most common morphological appearance of vascular dementia?

Answer 47

large vessel infarcts scattered throughout hemispheres | atheroma of large cerebral arteries provoke thromboembolism

Question 48

less common morphological appearance of vascular dementia?

Answer 48

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