1. CNS infections can be caused by bacteria, viruses, fungi, parasites, or prions. Common bacterial infections include meningitis caused by streptococcus pneumoniae, neisseria meningitidis, and listeria monocytogenes. 2. Viruses that can cause CNS infections include poliovirus, rabies virus, herpes simplex virus, measles (subacute sclerosing panencephalitis), and JC virus (progressive multifocal leukoencephalopathy). 3. Fungal infections like cryptococcosis and parasitic infections including malaria, toxoplasmosis, and trypanosomiasis can also infect the CNS.

1. CNS Infections
Dr. ADDISU (MD,MPH)
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2. CNS infection: etiology
1. BACTERIAL:
• Acute (pyogenic bacteria)
• Chronic- granulomatous eg. TB
2. VIRAL: acute & persistent
3. Miscellaneous
• FUNGAL eg. Cryptococcosis
• PROTOZOAL eg. malaria, toxoplasmosis, trypanosomiasis,
amoebic
• METAZOAL eg. cysticercosis, hydatid cyst
• TRANSMISSIBLE AGENT (PRION) DISEASES
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3. Routes of infections
• Hematogenoous (most common)
• Local extension: middle ear, sinuses
• Direct implantation: trauma, iatrogenic
• Peripheral nerves: Rabies & Herpes zoster
• Infections spread by CSF
• Variations in CSF protein, sugar & presence of
inflammatory cells => help to establish the
diagnosis of CNS infection
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4. Acute bacterial infections
 PURULENT (SEPTIC) MENINGITIS:
• Inflammation of the arachnoid mater and CSF within the
subarachnoid space => Meningo-encephalitis
• E. coli, H. influenza, N. meningitidis, etc
• headache,projectile vomiting , neck stiffness (from irritation
of spinal nerve roots), fever, and clouded consciousness
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5. Meningitis
• Newborn
– Streptococci (Group B)
– E. Coli
– Klebsiella-enterobacter
– Listeria monocytogenes
• Children, adults
– Str. pneumoniae
– Neisseria meningitidis
– Haemophilus influenzae
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6. …
• Typical CSF findings low glucose, high protein, and many
PMN's. A gram stain should be done to identify organisms
• Release of cytokines => meningeal inflammation & brain
swelling may be rapid and fatal
• In Gram negative infections => endotoxic shock => severe
hypotension and hypoxic brain damage
• In meningococcal infection, organisms &/or toxins lead to
vascular damage and DIC => petechial haemorrhages =>
hemorrhagic necrosis of the adrenal glands (Waterhouse-
Friderichsen syndrome)
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7. Acute Meningitis
• Fever
• Headache
• Altered mental status
• Neck stiffness
• Projectile vomiting
lumbar puncture
2 of 4 in 95%
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8. Spinal tap CSF Normal
water clear
pressure 0 – 10 – 15 mmHg
cells: few < 5 l
lymphocytes/mm3
protein small amount
glucose small amount
Meningitis
Cloudy, purulent
Pressure: increased
Cells: up to 90‘000
neutrophils
Protein ;increased
Glucose;decreased
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9. Results of Cerebrospinal Fluid Testing.
Samuels MA et al. N Engl J Med 2007;357:1957-1965.
Substance CSF Plasma Ratio
CSF/plasma
Na+ [meq/kg
H2O]
147.0 150.0 0.89
K+ [meq/kg H2O] 2.9 4.6 0.62
Mg++ [meq/kg H2O] 2.2 1.6 1.39
Ca++ [meq/kg H2O] 2.3 4.7 0.49
Osmolality [mosm/kg H2O] 289.0 289.0 1.0
Protein [mg/dl] 20.0 6000.0 0.003
Glucose [mg/dl] 64.0 100.0 0.64
Cholesterol [mg/dl] 0.2 175.0 0.001
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10. Neisseria meningitidis
Gram –negative
„Meningococcus“
Streptococcus
pneumoniae
Gram-positive
„Pneumococcus“
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11. Purulent meningitis
• Within 24 hours purulent exudate appears on the surface of
the brain => meningoencephalitis => ventriculitis and
choroid plexitis => ventricular empyema => periventricular
necrosis & vasculitis (leading to thrombosis and occlusion)=>
multiple small infarcts “characteristic & early in neonates”
• As early as 48 hours leptomeningeal fibroblastic proliferation
commences => occlusion of the exit foramina of the 4th
ventricle, obliteration of subarachnoid cisterns, or the
arachnoid villi over the convexities=> hydrocephalus
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12. Brain abscess
• Raised intracranial pressure, and/or seizures
• Site dependent on routes of infection
• Post-traumatic: adjacent to site of trauma
• Direct spread: frontal sinusitis => frontal lobe
• Haematogenous => usually multiple, often occipital
lobe or along boundary zones
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13. Epidural & subdural empyema
• Subdural empyema is usually 20 to sinus or
middle ear infection
• Epidural empyema common in the spine
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14. Tuberculous meningitis
• Meningeal exudate (basal) & small
"tubercles" (granulomas)
• Granulation tissue with fibroblasts =>
obstructive hydrocephalus
• Obliterative arteritis of leptomeningeal
vessels => necrosis
• Tuberculomas: single /multiple and
simulating brain tumours
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15. NEUROSYPHILIS
• Tertiary stage & 10% in untreated
• Meningovascular disease => obliterative
endarteritis => infarction
• Parenchymatous neurosyphilis (low grade
encephalitis) => neuronal loss and gliosis.
• Frontal lobes => general paralysis of the insane
(GPI)
• Demyelination of posterior columns of the spinal
cord => tabes dorsalis
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16. VIRAL INFECTIONS
• Meningitis, encephalitis or myelitis
• Immunoallergic reactions perivenous
demyelination or encephalitis following
rabies vaccination
• Actual invasion of the CNS by the virus
• Persistent (slow viral) infections =>
degeneration of neurons/myelin
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17. Pathology of viral infections
• Predominantly in grey matter
• Neuronal death & neuronophagia
• Microglial clusters, lymphoplasmacytic
perivascular infiltates
• Viral inclusion bodies (intranuclear or
intracytoplasmic) in neurones or glia
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18. Acute viral encephalomyelitis
• POLIOVIRUS attacks neurones of the anterior horns,
brain stem motor nuclei, and motor cortex =>
Wallerian degeneration of axons and neurogenic
atrophy of muscles
• RABIES - the virus enters via peripheral nerves;
diagnostic intracytoplasmic inclusions in pyramidal
neurones (Negri bodies)
• HERPES SIMPLEX ENCEPHALITIS - pantropic reaction
=> acute necrotising encephalitis
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19. Subacute & chronic (persistent) viral
infections
Subacute sclerosing panencephalitis (SSPE)
 Children, following measles, atrophic brain and
death within 1-2 yrs
Progressive multifocal leukoencephalopathy (PML)
20 to JC virus polyomavirus and in
immunosuppressed individuals (eg, AIDS)
 Virus destroys oligodendroglial cells => focal
demyelination
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20. HIV/AIDS: HIV specific damage
• HIV encephalopathy: multinucleate giant cell
• HIV encephalitis (HIVE): multiple
microgranulomatous foci
• HIV leucoencephalopathy (HIVL) => diffuse or
focal loss of myelin, reactive astrogliosis,
macrophages and multinucleate giant cells
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21. HIV-ASSOCIATED PATHOLOGY
• Diffuse myelin palor, Vacuolar myelopathy or
leucoencephalopathy
• Diffuse poliodystrophy, Lymphocytic
meningitis, Spongiform encephalopathy
• Cerebral vasculitis, AIDS associated myopathy
& peripheral neuropathy
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22. CNS lesions in severe immunosuppression
• Glial nodule encephalitis
• PML infection
• Myelitis associated with herpes simplex type
2
• Toxoplasmosis and cryptococcal infection
• CNS lymphoma
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23. HIV HIV-associated
[opportunistic]
CNS Lymphoma
CNS and HIV
Papovavirus (J C Virus)
Progressive multifocal
leukencephalopathy
Toxoplasma Gondii
Cryptococcus
neoformans
HIV meningoencephalitis
(subacute, giant cells)
Intravascular B-cell
Lymphoma
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