HNS10 Pathology Of CNS Infection

Question 1

Infection of CNS

Answer 1

1. Osteitis (bone infection)
2. Extradural abscess (usually due to trauma)
3. Subdural abscess (usually due to trauma)
4. Leptomeningitis (inflammation of arachnoid and pia mater)
5. Intracerebral abscess
6. Ventriculitis

Question 2

Bacterial meningitis

Answer 2

Pathology
1. Pus in subarachnoid space (particularly prominent over vertex and base of brain)
—> spread to ventricles and choroid plexus
—> extend over posterior aspect of spinal cord
2. Petechial haemorrhages (bleeding under skin) + focal infarction may be seen

Microscopy:

1. Subarachnoid space filled with ***polymorphs, later lymphocytes, plasma cells, macrophages
2. Causative organism can be identified by Gram stain
3. Small abscesses may be seen within white matter

• Complications:
  1. Inflammatory exudate —> fibrosis —> thickening / adhesion of meninges —> **obliteration of subarachnoid space —> **Hydrocephalus

2. ***Entrapment of cranial nerves by fibrosis —> Cranial nerve palsies (CN2, 6, 7, 8)
3. ***Septic thrombosis of cerebral vessels in subarachnoid space —> Cerebral infarction
4. Infarction / infection of parenchyma —> **Epilepsy (unstable electrical activity due to fibrous scar), Mental retardation, **Focal neurological disorder e.g. Hemiplegia, Spasticity

Question 3

Intracerebral abscesses

Answer 3

Sites:

• Epidural
• Subdural
• Intracerebral (mainly haematogenous)

Routes:

• Adjacent sepsis (e.g. Otitis media)
• Direct penetrating injuries
• Haematogenous (e.g. infective endocarditis, lung abscesses)

Pathology:
Initial acute inflammation with polymorph infiltration
—> Tissue necrosis + Pus formation
—> Fibrous capsule develops slowly around site of infection and necrosis (CT: hypovascular rim with necrotic centre)
—> surrounding brain develops Gliosis (proliferation/hypertrophy of glial cells)
—> Abscess gradually increase in size
—> **rupture into ventricle / at the surface of brain
—> **Cerebral herniations (e.g. transtentorial herniation of parahippocampal gyrus)
—> 70% who survive cerebral abscess develop epilepsy

Question 4

Tuberculous meningitis

Answer 4

Always secondary to tuberculosis in other body parts

• common in young and very old
• complication of miliary tuberculosis / active pulmonary tuberculosis / tuberculosis of spine
• more subtle presentation due to slow growing

Pathology:

1. Inflammatory exudate produced by tuberculous meningitis
   - gelatinous / **caseous
   - most abundant in **basal brain (cranial nerve exit)
   - around granuloma
   - contains mostly **lymphocytes, **plasma cells, **macrophages, **caseous material
   - over time will organise —> fibrosis —> extensive ***obliteration of subarachnoid space

• **2. Granulomatous inflammation elicited by secondary tuberculosis (with presence of specific immune response in the body)
• Small granulomas (central ***caseous necrosis surrounded by epithelioid histiocytes, 1-2mm in diameter) may be seen in pia-arachnoid
• Langhan’s giant cells, lymphocytes, fibrosis in periphery

3. Acid-fast bacilli demonstrated in necrotic areas by Ziehl-Neelsen stain

Complication:
1. Obstruction to CSF flow in subarachnoid space —> Hydrocephalus (expansion of ventricles)

2. Inflammation and fibrosis —> damage cranial nerve when they originate from base of brain —> Cranial nerve palsies (CN2, 6, 7, 8)
3. **Chronic inflammation —> intimal proliferation —> luminal narrowing of cerebral arteries —> **Endarteritis obliteran —> superficial infarcts in adjacent brain tissue
4. Infarction / infection of parenchyma —> Epilepsy, Mental retardation, Focal neurological disorder e.g. Hemiplegia, Spasticity

Diagnosis:
1. Examination of CSF
—> histological picture of granulomatous inflammation + demonstration of bacilli in granuloma
—> lymphocytes, low glucose, very high protein
2. CSF smear / culture takes time (rare can identify)
3. Finding active tuberculosis in other body parts
4. Brain biopsy during shunting procedure for treatment of hydrocephalus

Question 5

Tuberculomas

Answer 5

• Local encapsulated caseous mass in brain —> present as space-occupying lesion —> space occupying effect
• single / multiple
• Morphology same as granuloma
• obstruct CSF flow if near ventricles / cause ↑ ICP

Question 6

Fungal meningitis

Answer 6

Usually opportunistic, associated with underlying condition that impair cellular immune responses e.g. malignant lymphoma

Cryptococcus neoformans meningitis (can also affect healthy individuals):

• Spherical yeast in Indian ink preparation of CSF specimens
• Thick mucoid capsule of yeast stained by PAS stain
• Small cysts (up to 3mm diameter) found in cortex / deeper down
• Histology: inflammatory infiltrate containing abundant polymorphs + occasional granulomas (similar to tuberculosis)

Candida albicans, Aspergillus and Actinomyces rarely cause meningitis

Question 7

Pathophysiology of Viral CNS infection

Answer 7

Result of:

1. ***Cytopathic effects from direct invasion of nervous system OR
2. Accompanying / delayed ***immunological response to viral invasion (post-viral encephalitis/ polyneuropathy)

Viral CNS disease:

1. Viral meningitis
2. Viral encephalitis
3. Post-infectious encephalitis

Question 8

1. Viral meningitis

Answer 8

• Infiltration of ***leptomeninges by mononuclear cells

- Perivascular ***lymphocytic cuffing in the superficial layers of cerebral cortex

Question 9

2. Viral encephalitis

Answer 9

• large no. of causative viruses —> but very similar pathological features —> but severity / distribution throughout CNS depend upon the virus
• e.g. herpes simplex encephalitis: mainly involve temporal lobe (antiviral can be prescribed early)
• e.g. poliomyelitis: anterior horn cells of spinal cord
• **Histology:
  1. Lymphocytic and plasma cells infiltration (characteristic), restricted to perivascular region + meninges —> ***Perivascular mononuclear cell cuffing

2. Widespread proliferation of ***Microglial cells recognisable by their rod-shaped nuclei, sometimes grouped to form microglial scars
3. Infected / dead neurons ingested by Microglia / Macrophages —> ***Neuronophagia
4. ***Viral inclusions within glia and neuron seen in some acute viral encephalitis —> detected by electron microscopy, immunofluorescence, immunoperoxidase staining

Complication:

• Scoliosis (poliomyelitis)
• Atrophy of limb (poliomyelitis)
• Malformation of brain (cytomegalovirus, if infected during pregnancy)

Question 10

3. Post-infectious encephalitis

Answer 10

• follow vaccination / measles / varicella / influenza virus infection
• prognosis usually good
• ***Autoimmune attack
• Histology:
  1. Widespread small foci of perivascular tissue destruction (myelin sheath destroyed to greater extent than axons) —> plaques of **demyelination usually found around vessels with **lymphocytic cuffing
  2. **Astrocytic proliferation seen in later stage —> leaving **perivascular gliosis

Question 11

Aseptic meningitis

Answer 11

-ve bacteriologic culture of CSF —> does not exclude bacterial nature

Causes:

• Mycobacterial —> slow growing bacteria
• Viral
• Fungal
• Partially treated bacterial (prior antibiotic treatment)
• Leptospirosis —> slow growing bacteria

Question 12

Other infectious agents affecting CNS

Answer 12

1. Neurosyphilis
2. HIV

Protozoal / parasitic infection:

1. Amoebic meningoencephalitis
2. Cerebral toxoplasmosis (originate from cats faeces)
3. Cerebral malaria
4. Cysticercosis

Prion diseases:

1. Creutzfeldt-Jakob disease (unknown source)
2. Kuru
3. Bovine spongiform encephalopathy

Pathology of prion diseases:

1. Neuronal loss
2. Spongiform encephalopathy
3. Amyloid plaque containing prionic protein

Question 13

Virus and CNS

Answer 13

1. Neurotrophic virus
   - poliovirus
   - rabies
   - herpes simplex
2. Slow virus
   - subacute sclerosing panencephalitis
   - progressive multifocal leukoencephalopathy
3. Congenital
   - CMV
   - rubella
4. Perivenous encephalomyelitis
   - post-infectious / post-vaccinal encephalomyelitis
   - acute necrotising haemorrhagic leukoencephalitis
5. Others
   - multiple sclerosis
   - Reye’s syndrome