By which 3 routes can microorganisms gain entry to the CNS?
1. Direct spread - e.g. middle ear infection, base of skull fracture
2. Blood-borne - e.g. sepsis, infective endocarditis
3. Iatrogenic - e.g. V-P shunt, surgery, lumbar puncture
What is meningitis?
Life-threatening inflammation of the leptomeninges (pia + arachnoid), with or without septicaemia.
Suggest common causative organisms of meningitis in different age groups.
Neonates: E. coli, L. monocytogenes
2-5 yrs: H. influenzae type B (HiB)
5-30 yrs: N. meningitides
> 30 yrs: S. pneumoniae
Describe a common cause of chronic meningitis and the consequence of this.
Infection of meninges by miliary TB: granulomatous inflammation... fibrosis of meninges... cranial nerve entrapment and palsy.
Describe possible complications of meningitis.
1. cerebral abscess (needs drainage but risky)
2. subdural empyema (pus in subdural space, difficult to treat as no blood supply)
3. epilepsy (neuronal foci that don't develop properly)
4. cerebral infarction... neurological deficit
5. death (swelling... RICP)
Systemic (if associated with septicaemia):
6. inflammatory shock
What is encephalitis? Which organisms can cause this?
Inflammation of CNS tissue/parenchyma, classically viral - headache, nausea, some photophobia (can be mild or severe).
Involves neuronal cell death by virus - forms inclusion bodies, and lymphocytic inflammatory reaction. E.g.
- temporal lobe: herpes virus
- spinal cord motor neurones: polio
- brain stem: rabies
Explain the pathophysiology of prion diseases.
Prion proteins (PrP) are normal constituents of synapses. In disease, mutated PrP (sporadic, familial or ingested) interact with normal PrP causing them to undergo conformational change (i.e. become abnormal)... these aggregate and cause neuronal death and 'holes' in grey matter - SPONGIFORM ENCEPHALOPATHIES.
Name an example of prion disease.
Variant Creutzfeld-Jacob disease (mad cow disease) associated with BSE - marked accumulation of protease-resistance prion protein in brain tissue.
13-14 months illness duration. Symptoms:
- prominent psychiatric/behavioural symptoms
- painful dyesthesiasis
- delayed neurologic signs
What is dementia? Name the 4 different types.
Aquired global impairment of intellect, reason and personality without impairment of consciousness.
1. Alzheimer's (50%) - sporadic/familial, early/late
2. Vascular dementia (20%)
3. Lewy body
4. Picks disease
Which 2 hypotheses underpin the patholphysiology of Alzheimer's?
Loss of cortical neurones due to damage by:
1. amyloid plaques - foci of enlarged axons, synaptic terminal and dendrites with amyloid deposition in vessels in centre of plaque
2. neurofibrillary tangles - intracellular twisted filaments of hyperphosphorylated Tau protein (normally binds and stabilises microtubules)
Explain why early onset Alzheimer's is commonly seen in Down Syndrome.
Chromosome 21 contains genes involved in amyloid protein production:
- amyloid precursor protein (APP) gene
- presenilin (PS) genes 1 and 2 - code for components of secretase enzyme which breaks down amyloid
Mutation of these genes causes incomplete APP breakdown and thus amyloid deposition.
What is the normal intracranial pressure? Why can this change in normal conditions and how are these changes compensated for?
- Normal ICP = 5-15 mmHg
- Coughing and straining increases to 20 mmHg but only significant if increase in maintained for several minutes.
- Compensation mechanisms to maintain normal pressure: 1. reduce blood volume
2. reduce CSF volume
3. spatial - brain atrophy
What is the maximum ICP before blood flow to brain is compromised?
If ICP greater than 60 mmHg, too hard to pump blood to brain as not enough pressure difference. Would then have to increase systolic pressure. So in brain trauma Ps, measure systolic BP to check for RICP.
What are the pathologic effects of a space occupying lesion in the brain?
i. Deformation/destruction of brain around lesion...
ii. displacement of midline structures - loss of symmetry...
iii. brain shift resulting in internal herniation
Name the types of herniation.
What type of herniation is this? What is the clinical consequence?
SUBFALCINE: cingulate gyrus pushed under free edge of falx cerebri.
Causes compression of anterior cerebral artery... ischaemia of medial parts of frontal and parietal lobes... infarction.
What does the large arrow show? What is the clinical consequence?
TENTORIAL HERNIATION: uncus/medial part of parahippocampal gyrus through tentorial notch.
1. damage to ipsilateral occulomotor n. (e.g. blown pupil)
2. occlusion of blood flow in posterior cerebral and superior cerebellar arteries
3. frequently fatal due to secondary haemorrhage into brainstem - DURET haemorrhage
Common mode of death in those with large brain tumours and intracranial haemorrhage.
What does the small arrow show?
TONSILLAR HERNIATION: cerebellar tonsils pushed through foramen magnum, compressing brainstem (rapid death)
What is the most common type of tumour of the brain?
Metastases from other tumours
Name a type of benign tumour arising in the brain.
Meningeal origin - MENINGIOMA
What is the more common type of malignant tumour arising in the brain?
Astrocyte origin: ASTROCYTOMA (from grade 1 - more often in paeds, surgically treatable, to grade 4 - very aggressive, death in 6 mths)
Spread along nerve tracts and through subarachnoid space. Often present with secondary spinal tumour.
What is a stroke and what are the 2 main categories?
Stroke = sudden event producing a disturbance of CNS function due to vascular disease.
1. cerebral infarction - 85%
2. cerebral haemorrhage - 15%
Most commonly caused by embolism (heart - AF, mural thrombus; carotid atheroma; aneurysm...) but can be from thrombosis (over atheromatous plaque).
What are the 2 types of cerebral infarct?
1. regional - named cerebral artery of carotid
2. lacuna (<1cm) - small infarcts in deep penetrating arteries, associated with hypertension. Commonly affect basal ganglia.
Name the 2 possible sites of cerebral haemorrhage.
1. intracerebral haemorrhage - produces SOLs & RICP: associated with:
- hypertensive vessel damage
- Charcot-Bouchard aneurysms (microaneurysms in small brain vessels)
- amyloid deposition around cerebral vessels in elderly
- may be inherited
2. subarachnoid haemorrhage - sited at branching points in circle of Willis
- rupture of berry aneurysms
- pathogenesis poorly understood - male sex, hypertension, atheroma, links to other diseases
A P presents with sudden severe headache (thunderclap), or a sentinel headache, followed by loss of consciousness. What is the likely diagnosis?
Subarachnoid haemorrhage (often instantly fatal)