Meningitis & CNS Infections — Pathology

Infections of the CNS are a perennial NEET PG favourite because each organism leaves a signature footprint — a CSF pattern, an inclusion body, an imaging clue, or an eponymous lesion. This note ties the pathology to the bug, the age, the CSF, and the management so you can answer one-liners and image-based questions cold.

Definition & anatomical classification

CNS infections are classified by the anatomical compartment involved, because the compartment dictates the clinical picture and the CSF findings:

Term	Site of inflammation	Hallmark feature
Leptomeningitis ("meningitis")	Pia + arachnoid (subarachnoid space)	Neck stiffness, CSF abnormal
Pachymeningitis	Dura mater	Rare; TB, syphilis, IgG4 disease
Encephalitis	Brain parenchyma	Altered sensorium, seizures, focal deficits
Meningoencephalitis	Meninges + parenchyma	Combined picture (common in viral & TB)
Cerebral abscess	Focal parenchymal pus collection	Ring-enhancing mass, focal signs
Myelitis	Spinal cord	Para/quadriparesis, sensory level

High-yield: Meningitis irritates meninges → neck rigidity, Kernig & Brudzinski signs. Encephalitis affects parenchyma → altered consciousness, seizures, focal deficits. The overlap zone is meningoencephalitis.

Acute pyogenic (bacterial) meningitis

Pathology

The hallmark is a suppurative (neutrophilic) exudate in the subarachnoid space, most marked over the basal surface and cerebral convexities. The exudate may extend into the ventricles. Vessels traversing the exudate show vasculitis → thrombosis → infarction. Gross brain shows congested, opaque, oedematous leptomeninges with pus.

Aetiology by age (most-tested table)

Age group	Commonest organisms
Neonates (0–1 mo)	Group B Streptococcus (S. agalactiae), E. coli, Listeria monocytogenes
Infants & children	Streptococcus pneumoniae, Neisseria meningitidis, (H. influenzae b — now rare post-vaccine)
Adolescents/young adults	Neisseria meningitidis, S. pneumoniae
Elderly (>60) / immunocompromised	S. pneumoniae, Listeria, Gram-negative bacilli
Post-neurosurgery / shunt / trauma	Staphylococcus aureus, coagulase-negative staph, Gram-negatives
Basilar skull fracture / CSF leak	S. pneumoniae

High-yield: Streptococcus pneumoniae is the single commonest cause of bacterial meningitis overall (all ages combined). Listeria is the buzzword for neonates, pregnant women, elderly, and immunosuppressed (T-cell defects).

Clinical features

Classic triad: fever + neck stiffness + altered mental status (all three present in <50%). Headache, photophobia, vomiting. Meningococcaemia adds a non-blanching petechial/purpuric rash and may progress to Waterhouse–Friderichsen syndrome (bilateral adrenal haemorrhage + DIC + shock).

Bedside signs: Kernig (resistance/pain on knee extension with hip flexed), Brudzinski (passive neck flexion → involuntary hip/knee flexion), nuchal rigidity, jolt accentuation of headache.

Diagnosis — CSF is the investigation of choice

Approach: clinical suspicion → check for raised ICP/focal signs → CT head if indicated → lumbar puncture → CSF analysis + culture → start empirical antibiotics (do NOT delay for imaging).

High-yield: CSF culture is the gold standard / confirmatory test. Gram stain gives a rapid clue. CSF lactate >3.5 mmol/L and very high protein favour bacterial.

Management / drug of choice

Empirical: Ceftriaxone (3rd-gen cephalosporin) + Vancomycin (covers resistant pneumococcus). Add Ampicillin if Listeria is a concern (neonates, elderly, pregnant, immunocompromised). Dexamethasone before/with first antibiotic dose reduces mortality and hearing loss in pneumococcal meningitis (and historically H. influenzae).

CSF interpretation — the master table

This table is the single most examined block in CNS infection pathology.

Parameter	Normal	Bacterial (pyogenic)	Viral	TB	Fungal (Cryptococcal)
Appearance	Clear	Turbid/purulent	Clear	Clear/cobweb	Clear/viscid
Predominant cell	–	Neutrophils ↑↑↑	Lymphocytes	Lymphocytes	Lymphocytes
Cell count /µL	0–5	1000–5000+	10–500	50–500	20–500
Protein	15–45 mg/dL	↑↑ (>100)	Normal/mild ↑	↑↑↑ (very high)	↑
Glucose (CSF:plasma)	~0.6	↓↓ (<0.4)	Normal	↓	↓
Pressure	10–20 cm	↑	Normal/↑	↑	↑↑ (very high)
Special	–	Gram stain, culture	PCR	ADA↑, cobweb clot, AFB/CBNAAT	India ink, CrAg

High-yield mnemonic — "Bacterial = Big neutrophils, Low sugar": Bacterial & TB & fungal → low glucose; Viral → normal glucose. This single fact resolves most CSF MCQs.

High-yield: A cobweb / spider-web clot on standing CSF + markedly raised protein + low glucose + lymphocytes = tuberculous meningitis. ADA elevated; CBNAAT (GeneXpert) is the modern confirmatory test.

Viral (aseptic) meningitis & meningoencephalitis

Pathology

Lymphocytic infiltrate in meninges/perivascular spaces (Virchow–Robin), microglial nodules, neuronophagia. Glucose is normal — the key separator from bacterial.

Causes & signatures

• Enteroviruses (Coxsackie, echovirus) — commonest cause of viral/aseptic meningitis overall.
• Herpes simplex virus (HSV-1) — commonest cause of sporadic fatal encephalitis; targets the temporal lobes (haemorrhagic necrosis). Histology: Cowdry type A intranuclear inclusions. EEG: periodic lateralised epileptiform discharges (PLEDs) over temporal lobe. MRI: temporal lobe oedema/haemorrhage. CSF PCR is diagnostic.
• Rabies — Negri bodies (eosinophilic cytoplasmic inclusions) in neurons, classically in hippocampal pyramidal neurons and cerebellar Purkinje cells. Hydrophobia, aerophobia. Virtually 100% fatal once symptomatic.
• Arboviruses (Japanese encephalitis) — major cause of epidemic encephalitis in India; thalamic involvement on MRI.
• Poliovirus — anterior horn motor neurons → flaccid paralysis.
• CMV — "owl's eye" intranuclear inclusions; immunocompromised/neonates.

High-yield: Negri bodies → Rabies. Cowdry A inclusions + temporal lobe haemorrhagic necrosis → HSV encephalitis (DOC: IV Aciclovir — start empirically on suspicion, do not wait for PCR). Owl's eye → CMV.

Inclusion body quick reference

Inclusion	Location	Disease
Negri body	Cytoplasm (hippocampus, Purkinje)	Rabies
Cowdry type A	Intranuclear	HSV, VZV
Owl's eye	Intranuclear + cytoplasmic	CMV
Microglial nodule + neuronophagia	Parenchyma	Viral encephalitis (general)

Fungal meningitis

Cryptococcal meningitis (most examined)

Cryptococcus neoformans — an encapsulated yeast acquired by inhalation (pigeon droppings); classic in AIDS (CD4 <100). Causes a chronic basal meningitis.

• India ink stain: halo (capsule excludes ink) around budding yeast — rapid but lower sensitivity.
• Cryptococcal antigen (CrAg) latex agglutination / lateral flow — most sensitive & specific; investigation of choice.
• Soap-bubble lesions: gelatinous mucoid material distends the Virchow–Robin perivascular spaces, classically in the basal ganglia — the "soap-bubble" appearance on imaging/gross pathology.
• Very high opening pressure → therapeutic LPs needed.
• DOC: Amphotericin B + Flucytosine (induction), then Fluconazole (consolidation/maintenance).

High-yield: India ink + soap-bubble (basal ganglia/Virchow–Robin) + AIDS = Cryptococcal meningitis. Mucicarmine stains the capsule pink/red.

Other fungi

• Mucormycosis (rhino-orbito-cerebral): broad, aseptate, right-angle branching hyphae; diabetic ketoacidosis. Angioinvasion → infarction.
• Aspergillus: septate, acute-angle (45°) branching; immunosuppressed.
• Candida: microabscesses in immunocompromised/neonates.

Cerebral (brain) abscess

Pathophysiology & evolution

A focal suppurative parenchymal infection. Sources: contiguous spread (otitis media/mastoiditis → temporal lobe & cerebellum; sinusitis → frontal lobe), haematogenous (lung, cyanotic heart disease with right-to-left shunt — frontal/parietal, multiple), or direct (trauma/surgery). Commonest organisms: Streptococci (esp. S. anginosus/milleri) and anaerobes (Bacteroides); often polymicrobial.

Stages (stepwise): Early cerebritis (days 1–3) → Late cerebritis (days 4–9) → Early capsule (days 10–13) → Late capsule (>14 days). A central liquefied necrotic core is surrounded by a collagenous fibroblast-derived capsule, granulation tissue, gliosis, and oedema.

Imaging & clinical

• Ring-enhancing lesion on contrast CT/MRI with surrounding oedema.
• MRI diffusion-weighted imaging (DWI): abscess shows restricted diffusion (bright on DWI, dark on ADC) due to viscous pus — distinguishes abscess from cystic/necrotic tumour (which does NOT restrict).
• Features: headache, focal deficit, seizures; fever may be absent. Raised ICP.

High-yield: Ring enhancement + central DWI restriction = abscess (not tumour). LP is contraindicated when a mass lesion / raised ICP is suspected — risk of herniation.

Management

Aspiration/excision + antibiotics (ceftriaxone/cefotaxime + metronidazole ± vancomycin). Treat the source.

Tuberculous meningitis (high-yield Indian context)

A subacute basal exudative meningitis. Gelatinous exudate at the base traps cranial nerves (CN VI palsy commonest) and obliterates basal cisterns → communicating hydrocephalus. Vasculitis → infarcts (basal ganglia/internal capsule). Tuberculomas are parenchymal granulomas.

• Pathology: caseating granulomas with Langhans giant cells.
• CSF: cobweb clot, lymphocytic, very high protein, low glucose, ADA elevated, AFB/CBNAAT positive.
• DOC: standard 4-drug ATT (HRZE) + corticosteroids (reduce mortality/complications).

High-yield: Basal meningitis → cranial nerve palsies + hydrocephalus is the TBM signature. Steroids are indicated in TBM, pneumococcal, and HSV (the last with aciclovir).

Prion disease (Creutzfeldt–Jakob disease) — the "different" one

Not a classic infection but tested alongside CNS pathology. Spongiform encephalopathy — vacuolation of neuropil, no inflammation, no inclusion bodies. Caused by misfolded prion protein (PrPˢᶜ). Rapidly progressive dementia + myoclonus; EEG shows periodic sharp-wave complexes; 14-3-3 protein in CSF; MRI cortical ribboning / pulvinar sign (vCJD).

High-yield: Spongiform change + no inflammation + myoclonus + periodic EEG = CJD. Resistant to standard sterilisation.

Key differentials & how to separate them

Clue	Most likely diagnosis
Neutrophilic CSF + low glucose, turbid	Bacterial (pyogenic) meningitis
Lymphocytic CSF + normal glucose	Viral meningitis
Lymphocytic + very high protein + low glucose + cobweb	TB meningitis
India ink positive + AIDS	Cryptococcal meningitis
Temporal lobe haemorrhage + Cowdry A	HSV encephalitis
Negri bodies + hydrophobia	Rabies
Ring-enhancing + DWI restriction	Pyogenic abscess
Adrenal haemorrhage + purpura + shock	Meningococcaemia (Waterhouse–Friderichsen)

Recently asked / exam angle

• "Soap-bubble lesions in basal ganglia" → identify organism = Cryptococcus neoformans (gelatinous capsule expanding Virchow–Robin spaces).
• "Negri bodies are seen in which neurons?" → Hippocampal pyramidal + cerebellar Purkinje cells (Rabies).
• "Commonest cause of bacterial meningitis in neonates" → Group B Streptococcus (S. agalactiae).
• "Cowdry type A inclusions + temporal lobe necrosis" → HSV-1 encephalitis; DOC aciclovir.
• CSF table MCQ: given values, classify bacterial vs viral vs TB (glucose is the discriminator).
• "India ink stain is used for" → Cryptococcus.
• Image of ring-enhancing lesion with DWI restriction → brain abscess vs necrotic tumour (abscess restricts).
• "Waterhouse–Friderichsen syndrome" → N. meningitidis, bilateral adrenal haemorrhage.
• "Organism causing meningitis with low CD4 count / AIDS" → Cryptococcus (also Listeria, Toxoplasma for ring lesions).
• Mucormycosis hyphae → broad aseptate right-angle branching in DKA patient.

Rapid revision

1. S. pneumoniae = commonest bacterial meningitis overall; GBS/E. coli/Listeria = neonates.
2. Bacterial CSF: neutrophils ↑, glucose ↓, protein ↑, turbid; culture is gold standard.
3. Viral CSF: lymphocytes, normal glucose; enterovirus commonest, PCR diagnostic.
4. Negri bodies → Rabies (hippocampus, Purkinje cells).
5. Cowdry A + temporal lobe haemorrhage → HSV encephalitis; DOC IV aciclovir.
6. India ink + soap-bubble basal ganglia → Cryptococcus; CrAg most sensitive; DOC Ampho B + flucytosine.
7. Cobweb clot + ADA↑ + low glucose + lymphocytes → TB meningitis; CBNAAT confirms; add steroids.
8. Brain abscess: ring-enhancing + DWI restriction; otitis → temporal lobe/cerebellum; Strep + anaerobes.
9. LP contraindicated with raised ICP/focal mass — image first; never delay antibiotics for imaging in suspected bacterial meningitis.
10. Empirical bacterial meningitis Rx = Ceftriaxone + Vancomycin (± Ampicillin for Listeria) + early dexamethasone.
11. Waterhouse–Friderichsen = meningococcal sepsis + bilateral adrenal haemorrhage + DIC.
12. CJD = spongiform, no inflammation, myoclonus, periodic EEG, 14-3-3 protein.