Infections of the central nervous system (meningitis, encephalitis)

1. Routes of Infection

A) Hematogenous Spread

• Most common means of entry.
• Via anastomoses between facial veins + venous sinuses of skull (retrograde).

B) Direct Implantation

• Penetrating trauma.
• Iatrogenic (via lumbar puncture needle).

C) Local Penetration

• Migration from nearby infection of skull/spine: sinusitis, dental infection, osteomyelitis, meningomyelocele.

D) Peripheral Nerves

• Pathway for rabies and herpes viruses.

2. Meningitis

Definition

• Inflammation of meninges within subarachnoid space.
• Meningoencephalitis = spread into brain parenchyma.

A) Acute Pyogenic (Bacterial) Meningitis

Etiology by Age

Age group	Pathogen
Newborns	Streptococcus agalactiae (GBS), E. coli, L. monocytogenes
Children + young adults	Neisseria meningitidis (meningococcus)
Older adults	Streptococcus pneumoniae, Listeria monocytogenes

Morphology

• Purulent exudate on meningeal surface.
• Thrombophlebitis.
• Parenchymal spread in severe cases.

Clinical Features

• Meningeal signs: headache, photophobia, stiff neck (nuchal rigidity), irritability.
• Kernig + Brudzinski signs.
• CSF: ↑↑ neutrophil granulocytes, ↑ protein, ↓ glucose.
• Therapy: antibiotics + steroids.

B) Aseptic (Viral) Meningitis

• Inflammation without bacterial source.
• Acute onset, usually self-limited.
• Pathogens: Echovirus, Coxsackievirus A/B, HSV-2, enteroviruses.
• Morphology: minimal lymphocytic infiltration of leptomeninges.
• CSF: ↑ lymphocytes, mild ↑ protein, normal glucose, negative bacteriology.
• Suspected pathogens often difficult to detect (serology, PCR).

C) Chronic Meningitis

Tuberculous Meningitis

• Symptoms: headache, fatigue, confusion, vomiting.
• Intraparenchymal mass = tuberculoma.
• Arachnoid fibrosis → communicating hydrocephalus.
• CSF: ↑ lymphocytes, ↑↑ protein, ↓ glucose.

Neurosyphilis

• Tertiary syphilis; invasion by Treponema pallidum.
• Progressive paralysis (general paresis): chronic meningoencephalitis 10–20 yr later.
• Tabes dorsalis: demyelination of dorsal columns of SC → loss of sensation, proprioception, discriminative touch.
• Argyll Robertson pupil (accommodates but does not react to light).

Neuroborreliosis

• Borrelia burgdorferi → Lyme disease.
• Transmitted by tick bite.
• Symptoms: aseptic meningitis, facial nerve palsies (Bell’s), polyneuropathy.

Fungal Meningitis

• Usually Cryptococcus neoformans (rarely Histoplasma capsulatum).
• Immunocompromised patients.
• May involve parenchyma (meningoencephalitis).
• Spreads into Virchow-Robin spaces → soap bubble-like cysts.
• Fulminant (fatal within 2 weeks) or indolent (months–years).
• CSF: encapsulated yeast on India ink.

3. Abscesses

A) Epidural Abscess

• Mainly streptococci/staphylococci.
• From frontal or mastoid sinusitis.
• Associated with focal osteomyelitis.

B) Subdural Empyema

• Polymicrobial (staphylococci + gram-negative anaerobes).
• Thrombophlebitis of bridging veins → infarction.

C) Cerebral Abscess (Parenchymal)

• Etiology:
  • Local invasion: sinusitis, mastoiditis.
  • Hematogenous: acute bacterial endocarditis, pneumonia.
  • Predisposing: chronic pulmonary inflammation, cyanotic heart disease.
• Symptoms: focal symptoms + signs of intracranial hypertension.
• Complications: meningitis, sinus thrombosis, ventriculitis.
• Imaging: ring-enhancing lesion.

4. Encephalitis (Parenchymal Infection)

Definition

• Inflammation of brain.
• Better termed meningoencephalitis (usually associated with meningitis).

General Morphological Features of Viral Encephalitis

• Perivascular + parenchymal mononuclear infiltrate.
• Microglial nodules.
• Neuronophagia (destruction of nerve cells by phagocytes).
• Characteristic inclusion bodies.

Viral Encephalitis

Herpes Viruses

• HSV-1:
  • Children + young adults.
  • Frontal + temporal lobe involvement → mood/memory/behavioral disturbances.
  • Necrosis + hemorrhage, perivascular infiltrate.
  • Cowdry type A inclusions.
• HSV-2:
  • Meningitis in adults, disseminated encephalitis in newborns (from genital herpes/vaginal infection).
• Varicella Zoster Virus (VZV):
  • Chickenpox → latency → shingles (painful vesicular eruption along dermatome).
  • Encephalitis in immunocompromised.
• CMV:
  • Fetuses: periventricular necrosis + calcification + microcephaly.
  • Immunocompromised adults: subacute encephalitis.
  • Owl’s eye inclusions.

Poliovirus

• Enterovirus → paralytic poliomyelitis → acute flaccid paralysis (anterior horn cells).
• Death from respiratory arrest.
• Post-polio syndrome after years → muscle weakness, pain, fatigue.

Rabies Virus

• Severe encephalitis transmitted by bite of rabid animal.
• Histology: Negri bodies (eosinophilic cytoplasmic inclusions in Purkinje + hippocampal neurons).
• Enters CNS by ascending along peripheral nerves.
• Extreme irritability → hyperalgesia, aggressiveness, seizures, hydrophobia.
• Maniac periods, coma, respiratory insufficiency.

HIV CNS Diseases

• Aseptic meningitis → primary infection.
• HIV encephalitis → virus in CD4⁺ mononuclear cells, histiocytes, microglia (microglial nodules + multinucleated giant cells).
• HIV-associated neurocognitive disorder (HAND) → cognitive dysfunction → dementia.

Progressive Multifocal Leukoencephalopathy (PML)

• JC virus (polyomavirus).
• Infects oligodendrocytes → demyelination.
• Asymptomatic infection during childhood → reactivation upon immunosuppression (HIV, natalizumab).
• Morphology: multifocal, irregular demyelination + oligodendroglial changes.
• Clinical: intractable, progressive focal symptoms.

Fungal Encephalitis

• Candida albicans: multiple microabscesses, no granulomas.
• Mucormycosis: hematogenous from sinonasal infection; DKA patients.
• Aspergillus fumigatus: septic hemorrhagic infarcts from thrombosis.

Parasitic Infections

• Cerebral toxoplasmosis (Toxoplasma gondii):
  • Newborns: hydrocephalus, intracranial calcification, chorioretinitis.
  • Immunocompromised adults: multiple ring-enhancing abscesses (tachyzoites/bradyzoites).
• Cysticercosis:
  • End-stage Taenia solium tapeworm.
  • Larvae → cysts in brain tissue; #1 cause of acquired epilepsy worldwide.

5. CSF Summary Table

Type	Cells	Protein	Glucose
Bacterial (pyogenic)	↑↑ Neutrophils	↑↑	↓↓
Viral (aseptic)	↑ Lymphocytes	Mild ↑	Normal
TB / Fungal	↑ Lymphocytes	↑↑	↓

💡 High-yield: Bacterial meningitis by age: newborns = GBS/E. coli/Listeria, children/young = N. meningitidis, older = S. pneumoniae + Listeria; CSF ↑↑ neutrophils, ↑ protein, ↓ glucose. Viral meningitis = enteroviruses/HSV-2; lymphocytes, normal glucose. Fungal = Cryptococcus (India ink, encapsulated yeast). HSV-1 encephalitis = temporal/frontal lobe (mood/memory). Rabies = Negri bodies in Purkinje/hippocampus; hydrophobia. CMV = periventricular calcification + microcephaly (fetus); owl’s eye inclusions. PML = JC virus, oligodendrocytes, immunosuppression. Toxoplasmosis = newborn calcifications/hydrocephalus, HIV patients = ring-enhancing abscesses. Cysticercosis (Taenia solium) = #1 cause of acquired epilepsy worldwide.