Neuropathology Flashcards
What are the causative organisms for (lepto)meningitis in different age groups?
Neonates: E. coli, L. monocytogenes,
2-5yrs: H. influenzae B
5-30yrs: N. meningitidis types
30yrs+ S. pneumoniae
What are the causative organisms in “chronic meningitis”?
M. tuberculosis = granulomatous inflammation fibroses meninges and entraps nerves
Give some possible complications from (lepto)meningitis.
Swelling —> raised ICP —> death
Cerebral infarct —> neurological deficit
Cerebral abscess (reduced immune function, do not seek help e.g. elderly, alcoholics)
Subdural empyema
Epilepsy
Systemic (septicaemia
Differentiate meningitis and encephalitis.
Encephalitis is classically viral, not bacterial
e.g. in CMV can have owl’s eye inclusions (replicating virions) on histology
Encephalitis affects brain parenchyma, not meningitis
What is the pathophysiology of prion disorders?
Mutated prion proteins (sporadic, familial, or ingested) interact with normal prion proteins to cause a post-translational conformational change
Aggregate forms which is extremely stable and causes neuronal death
Neuronal death forms “holes” in grey matter (spongiform encephalopathy) which causes a rapid onset of dementia-like presentation
note: prions are not infections (cannot be cultured)
What is the pathophysiology of Alzheimer’s disease?
Sporadic/familial, early/late
Exaggerated ageing process
Loss of cortical neurones causing a reduction in brain weight and cortical atrophy
Neuronal damage is caused by neurofibrillary tangles (intracellular twisted filaments of tau protein - tau normally stabilises microtubules but becomes hyperphosphorylated in Alzheimer’s)
Senile plaques form = “cotton wool” appearance with foci of enlarged axons, synaptic terminals, and dendrites with amyloid deposition in the centre of the plaque (forms “halo”)
note: amyloid deposition also occurs in Down’s syndrome (which causes early onset Alzheimer’s disease) and hereditary disorders (mutations causing incomplete breakdown of myeloid precursor protein)
What is the normal intracranial pressure? How does the brain attempt to compensate for raised intracranial pressure?
Normal ICP = 0-10mmHg (coughing and straining = 20mmHg)
Compensation mechanisms:
- brain atrophy
- reduced blood volume
- reduced CSF volume
Vascular mechanisms maintain cerebral blood flow as long as ICP
What damage is caused by expanding focal lesions in the brain?
Deformation/destruction of brain around the lesion
Sulci flattened against the skull
Displacement of midline structures causing loss of symmetry
Internal herniation)
Give some examples of causes of raised intracranial pressure.
Expanding focal lesions e.g.
- tumour
- haematoma
- abscess
- infarction —> oedema
Global increase in brain mass e.g.
- oedema
- inflammation (meningitis or encephalitis)
- trauma
Describe the events of subfalcine herniation.
Occurs the same side as the lesion
Cingulate gyrus is pushed under the free edge of the falx cerebri
Ischaemia of the medial frontal and parietal lobes and the corpus callosum (compression of the anterior cerebral artery)
Describe the events in tentorial herniation.
Uncus/medial part of parahippocampal gyrus (temporal lobe) herniates through tentorial notch
Damages occulomotor nerve, cerebral peduncles
Occludes posterior cerebral and superior cerebellar arteries
Causes Duret haemorrhages in midbrain/pons —> Cushing’s reflex (common mode of death in people with large brain tumours and intracranial haemorrhages)
Describe the events in tonsillar herniation.
Cerebellar tonsils (+/- medulla) pushed into foramen magnum —> compresses brainstem
Describe the progression of the presentation of raised intracranial pressure.
Prodromal phase:
- headache
- vomiting
- papilloedema
Acute phase:
- oculomotor nerve compression —> pupil dilatation
- brainstem compression —> coma
Compression of cerebral peduncles —> hemiparesis on same/opposite/both sides, decerebrate rigidity
Further herniation —> apnoea and cardiac arrest
Give some examples of benign and malignant brain tumours.
Benign tumours e.g. meningioma
Malignant tumours e.g. astrocytoma
- spread along the nerve tracts, through the subarachnoid space, spinal secondaries
- grade 1 = common in children, space-occupying lesion —> epilepsy
- grade 4 = adults, 3-6 month prognosis
Contrast primary and secondary mechanisms of head injury.
PRIMARY (due to force causing the injury) =
—> DIFFUSE = direct tearing to axons at sites of differing density (e.g. junction between white and grey matter), heals by gliotic scarring, rotational force is esp. severe
—> FOCAL DAMAGE (coup and contrecoup) = bruising/laceration of brain as it hits the inner surface of the skull + tearing of blood vessels —> haemorrhage
SECONDARY (reaction to primary damage itself, worsening the injury) e.g. bleeding into brain —> vasoconstriction —> secondary ischaemia
