Neuropathology Flashcards
What are astrocytes?
glial cells that can multiply as part of healing process (gliosis) or can give rise to brain tumours (astrocytomas)
What are the most sensitive neurons in adults?What does damage to them cause?
Hippocampal pyramidal cells
damage causes memory impairment
What cells are involved in movement coordination?
Purkinje cells of the cerebellum
4 causes of global cerebral ischaemia
low perfusion (atherosclerosis)
acute decrease in cerebral perfusion (cardiogenic shock)
chronic hypoxia (anaemia)
hypoglycaemia
3 causes of global hypoxia/ischaemia
severe hypotension
severe hypoglycaemia
prolonged seizures (1-2 hours)
Pathology of ischaemic stroke
liquefactive necrosis
red neurons (12 hours post-infarction)
necrosis (24 hours)
neutrophil infiltration (days 1-3)
microglial cell proliferation (days 4-7)
gliosis (weeks 2-3)
fluid-filled cystic space surrounded by gliosis
Causes of intracranial haemorrhage
hypertension
cerebral amyloid angiopathy
saccular aneurysms
vascular malformations
tumours
vasculitis
Intracerebral haemorrhage symptoms
severe headache
nausea
vomiting
coma
Meninges layers
dura mater
arachnoid mater
pia mater
What type of aneurysm rupture can cause a subarachnoid haemorrhage?
berry aneurysm
What does a lumbar puncture show in subarachnoid haemorrhage?
xanthochromia due to presence of bilirubin
What conditions can predispose to subarachnoid haemorrhage?
Marfan’s syndrome
Ehler-Danlos syndrome
Autosomal dominant polycystic kidney disease
What is an epidural haemorrhage?
collection of blood between the dura and the skull
Rupture of what causes an epidural haemorrhage?
middle meningeal artery
What is the weakest part of the skull?
Pterion - junction between 4 bones (frontal, parietal, greater sphenoid and squamous part of temporal bone)
What artery is the middle meningeal artery a branch of?
maxillary artery
What causes a subdural haemorrhage?
tearing of bridging veins which lie between dura and arachnoid
What does a subdural haemorrhage look like on CT scan?
crescent-shaped lesion
Name 3 traumatic brain injuries
coup/contrecoup (brain bruising due to contact of soft tissue with skull)
contusions
diffuse axonal injury
What causes diffuse axonal injury?
RTAs/blows to unsupported head
cerebrum glides back and forth, pivoting around brain stem
stretches axons
unconscious immediately after injury
What is herniation (brain)?
displacement of brain due to mass effect or increased intracranial pressure
Myelin function
insulates axons, improving the speed and efficiency of nerve conduction
means AP jumps from one node of Ranvier to the next
What is multiple sclerosis?
chronic demyelinating disease
What does a lumbar puncture show in MS?
increased lymphocytes
increased immunoglobulins with oligoclonal IgG bands and myelin basic protein
MS macroscopically
irregular, sharply demarcated grey areas in white matter
Describe subacute sclerosing panencephalitis
slowly progressing persistent infection caused by measles virus
infection in infancy with neurologic signs years later
progress debilitating encephalitis leading to death
viral inclusions within neurons and oligodendrocytes
Describe progressive multifocal leukoencephalopathy
JC virus infection of oligodendrocytes
immunosuppression leads to reactivation of latent virus
presents with rapidly progressive neurological signs (visual loss, weakness and dementia)
Describe central pontine myelinolysis
rapid intravenous correction of hyponatremia
occurs in severely malnourished patients
presents as acute bilateral paralysis
What are leukodystrophies? Name 3
Inherited, involve white matter, cause progressive demyelination
metachromatic leukodystrophy
Krabbe disease
Adrenoleukodystrophy (ALD)
What does thiamine deficiency cause?
Thiamine deficiency
Neurological complication of vitamin B12 deficiency
subacute combined degeneration of the spinal cord involving both ascending and descending tracts
- ataxia
- lower limb numbness
- tingling
- weakness
- paraplegia
Degeneration of what leads to dementia?
cortex
Degeneration of what leads to movement disorders?
basal ganglia
What is the most common degenerative disease of the CNS?
Alzheimer’s
What mutations are seen in familial cases of early onset Alzheimer’s disease?
presenilin 1+2 mutations
(Down’s syndrome also increases risk)
Macroscopic brain features with Alzheimer’s disease
brain atrophy
dilatation of lateral ventricles due to loss of brain tissue (hydrocephalus ex vacuo)
thinning of gyri and deepening of sulci
Microscopic features of an Alzheimer’s brain
neurofibrillary triangles (NFTs) = deposits of Tau filaments in neuronal body
senile plaques = contain amyloid beta deposits (congo red +ve, apple-green birefringence under polarised light)
granulovacuolar degeneration in neurons
cerebral amyloid angiopathy
What is the 2nd most common cause of dementia?
vascular dementia
What is Pick’s disease?
similar to Alzheimer’s but far less common
preferentially affects frontal + temporal lobes
behavioural + language symptoms arising early which eventually progress to dementia
Pathophysiology Parkinson’s disease
degenerative loss of dopaminergic neurons in the substantia nigra of the basal ganglia (which secrete dopamine)
nigrostriatal pathway of basal ganglia uses dopamine to initiate movement
Clinical features Parkinson’s disease (TRAP)
Tremor - pill rolling at rest, disappears with movement
Rigidity - leadpipe/cogwheel rigidity in extremities or axially
Akinesia/bradykinesia - slowing of voluntary movement, expressionless face
Postural instability + shuffling gait
Macroscopic brain of Parkinson’s
loss of pigment in substantia nigra
Microscopic features of Parkinson’s
round eosinophilic inclusions of alpha synuclein (Lewy bodies) in affected neurons
Huntington disease genetics
autosomal dominant
expanded trinucleotide CAG repeats in the huntingtin gene
Symptoms of normal pressure hydrocephalus
3 Ws
Wet (incontinence)
Wobbly (gait disturbance)
Wacky (dementia)
Pathophysiology of normal pressure hydrocephalus
increased CSF causing dilated ventricles, usually idiopathic and treated by ventriculoperitoneal shunt
Describe spongiform encephalopathy
normal neurons have a prion protein which has an alpha helical configuration
disease occurs when it is converted to a beta pleated sheet configuration
can convert normal prion into disease form
accumulation of abnormal prion protein causes vacuolar damage to neurons and glial cells (spongy degeneration)
Microscopic features MND
muscles undergo denervation atrophy due to loss of LMNs
small eosinophilic intranuclear inclusions called Bunina bodies may be seen in remaining LMNs
Pathogenesis MND
degeneration and loss of motor neurons in anterior horn + motor nuclei of brain stem, associated with gliosis + microglial activation
3 types of brain infections
meningitis
brain abscess
viral encephalitis
What is infected in acute bacterial meningitis?
infection of arachnoid membrane, subarachnoid space and CSF by bacteria
Bacterial meningitis most common organisms
streptococcus pneumoniae
neisseria meningitidis
Brain abscess presentation
headache, infection symptoms, focal neurological deficits, seizures
What are the most common primary tumours that metastasise to brain?
lung
breast
kidney
melanoma
Where do metastatic tumours occur in the brain?
multiple well-circumscribed lesions at the junction between the grey and white matter
Most common primary brain tumours in adults
glioblastoma
meningioma
schwannoma
Most common primary brain tumours in children
pilocytic astrocytoma
ependymoma
medulloblastoma
Describe glioblastoma
malignant high grade tumour of astrocytes (GFAP +ve)
usually arises in cerebral hemisphere
characteristically crosses corpus callosum - Butterfly lesion
Describe meningioma
derived from arachnoid cells
may present with seizures
benign CNS tumour
round mass attached to the dura, compresses but does not invade the cortex
Describe schwannoma
benign tumour of schwann cells
most commonly presents with deafness + tinnitus - CNVII at cerebellopontine angle
bilateral tumours in neurofibromatosis type 2
S100 +ve on immunohistochemistry
Describe oligodendroglioma
malignant tumour of oligodendrocytes
calcified tumour in white matter of frontal lobe
may present with seizures
fried egg appearance of cells on biopsy
Describe pilocytic astrocytoma
most common CNS tumour in children
benign tumour of astrocytes (GFAP +ve)
cystic lesion in cerebellum with mural nodule
Rosenthal fibres (thick eosinophilic astrocytic processes) with eosinophilic granular bodies)
Describe medulloblastoma
malignant tumour derived from granular cells of the cerebellum (neuroectoderm)
tumour grows rapidly and spreads via CSF
malignant small round blue cells on microscopy
Describe ependymoma
malignant tumour of ependymal cells
usually seen in children
arises in 4th ventricle + may present with hydrocephalus
perivascular pseudo-rosettes on microscopy
Describe craniopharyngioma
benign tumour which arises from epithelial remnants of Rathke’s pouch, above the pituitary
calcified supratentorial mass in child or young adult
compression of optic chiasm, causing bitemporal hemianopia
benign but can recur following resection
