Meningitis & Encephalitis

Inflammation of the leptomeninges (meningitis) versus inflammation of the brain parenchyma (encephalitis) — a high-yield Neurology pairing where the entire exam hinges on CSF analysis, organism-by-age, empiric therapy, and the temporal-lobe signature of HSV. Master the CSF table, the dexamethasone rule, and acyclovir, and you have most of the marks.

Definitions & basic distinction

• Meningitis — inflammation of the pia-arachnoid and the intervening subarachnoid space. Dominated by meningism: headache, neck stiffness, photophobia, fever. Sensorium is relatively preserved early.
• Encephalitis — inflammation of brain parenchyma. Dominated by altered mental status, behavioural change, focal deficits, and seizures. Fever may be present, but neck stiffness is variable.
• Meningoencephalitis — overlap; common in TB, listeria, and severe viral disease.

High-yield: The single best clinical discriminator — meningitis presents with meningism and a clear sensorium; encephalitis presents with altered behaviour/consciousness and seizures. HSV encephalitis is the encephalitis you must never miss.

Classification of meningitis

Type	Onset	Typical CSF picture	Common causes
Acute pyogenic (bacterial)	Hours–2 days	Neutrophilic, turbid	Pneumococcus, meningococcus, H. influenzae
Acute lymphocytic (viral/aseptic)	1–7 days	Lymphocytic, clear	Enteroviruses (commonest), HSV-2, mumps
Chronic	>4 weeks	Lymphocytic	TB, fungal (Cryptococcus), Brucella
Subacute	Days–weeks	Lymphocytic, low glucose	TB, partially treated bacterial, fungal

"Aseptic meningitis" = clinical/CSF meningitis with negative routine bacterial cultures — most often viral, but also includes partially treated bacterial, drug-induced (NSAIDs, IVIG, cotrimoxazole), and Mollaret (recurrent, HSV-2).

Etiology by age — the classic exam axis

Age group	Top organisms (mnemonic / notes)
Neonate (0–1 mo)	Group B Streptococcus (S. agalactiae), E. coli, Listeria monocytogenes
Infant/child	Pneumococcus, Meningococcus; H. influenzae type b (now rare post-Hib vaccine)
Adolescent/young adult	Neisseria meningitidis (epidemics, college hostels), Pneumococcus
Adult >50 / immunocompromised / pregnant	Pneumococcus, Listeria, Gram-negative bacilli
Post-neurosurgery / shunt / trauma	Staph aureus, coagulase-negative staph, Gram-negative rods, Pseudomonas
Basilar skull # / CSF rhinorrhoea	Pneumococcus (recurrent meningitis)

High-yield: Listeria covers the neonate AND the >50/immunocompromised/pregnant patient — both ends of the age spectrum. That is why ampicillin is added to the empiric regimen in these groups (cephalosporins do NOT cover Listeria).

Mnemonic for meningococcal/asplenia risk: encapsulated organisms = "Some Nasty Killers Have Some Capsule Protection Especially" — S. pneumoniae, N. meningitidis, Klebsiella, H. influenzae, Salmonella, group B strep, Pseudomonas, E. coli. Asplenic and complement (C5–C9 terminal pathway) deficient patients are prone to recurrent Neisseria infection.

Pathophysiology (bacterial)

Nasopharyngeal colonisation → mucosal invasion → bacteraemia (survival aided by polysaccharide capsule) → crossing the blood–brain barrier at choroid plexus/cerebral capillaries → multiplication in subarachnoid space (poor immune surveillance) → bacterial lysis releases cell-wall/LPS → cytokine surge (TNF-α, IL-1) → BBB breakdown, vasogenic + cytotoxic + interstitial oedema → raised ICP, reduced cerebral blood flow, vasculitis → infarction and neuronal injury.

This cytokine cascade is the rationale for adjunctive dexamethasone — it blunts the inflammatory response that itself causes hearing loss and neurological sequelae.

Clinical features

Bacterial meningitis classic triad = fever + neck stiffness + altered mental status (all three present in <50%, but ≥2 of fever/neck stiffness/headache/altered sensorium in ~95%).

Signs of meningeal irritation:

• Kernig sign — with hip flexed 90°, passive knee extension is resisted/painful (hamstring spasm).
• Brudzinski sign — passive neck flexion causes involuntary hip & knee flexion.
• Nuchal rigidity — resistance to passive neck flexion.

High-yield: Kernig and Brudzinski are specific but insensitive — their absence does NOT exclude meningitis. Jolt accentuation of headache (worsening on horizontal head rotation ~2–3/sec) is more sensitive.

Pointers to specific aetiology:

• Petechial/purpuric rash + DIC + adrenal haemorrhage → meningococcaemia (Waterhouse–Friderichsen syndrome).
• Recurrent meningitis → CSF leak (skull base #), complement deficiency, parameningeal focus.
• Cranial nerve palsies (esp. III, VI), focal deficits, basal involvement → TB meningitis.
• Seizures + temporal-lobe signs (aphasia, behavioural change, olfactory/gustatory hallucinations) → HSV encephalitis.

Encephalitis red flags: personality change, confusion, focal seizures, hemiparesis, autonomic instability. Anti-NMDA-receptor encephalitis — young woman, psychiatric symptoms → seizures → orofacial dyskinesias → autonomic instability; look for ovarian teratoma.

CSF analysis — the centrepiece

Parameter	Normal	Bacterial (pyogenic)	Viral (aseptic)	TB	Fungal (Cryptococcal)
Appearance	Clear	Turbid/purulent	Clear	Xanthochromic, cobweb clot	Clear/viscous
Opening pressure	10–18 cm H₂O	↑↑	Normal/mild ↑	↑	↑↑ (often very high)
Cells (predominant)	<5/µL	1000–5000, neutrophils	10–500, lymphocytes	50–500, lymphocytes	Lymphocytes
Protein	15–45 mg/dL	High (100–500+)	Normal/mildly ↑	Very high	High
Glucose (CSF)	45–80 (≥⅔ blood)	Low (<40)	Normal	Low	Low
CSF:blood glucose ratio	≥0.6	<0.4	Normal	<0.4	<0.4
Lactate	<2.1 mmol/L	High (>3.5)	Normal	High	High

High-yield (most asked): Bacterial = turbid, ↑neutrophils, ↑↑protein, ↓glucose. Viral = clear, lymphocytes, normal glucose. TB = cobweb (spider-web) clot on standing, very high protein, low glucose, lymphocytes. The TB cobweb clot is a pure recall favourite.

Special CSF clues:

• Low glucose with lymphocytes → think TB, fungal, Listeria, or partially treated bacterial (NOT typical viral).
• HSV encephalitis CSF → lymphocytic, RBCs/xanthochromia (haemorrhagic-necrotising), mildly raised protein, normal glucose; diagnose by CSF HSV PCR (sensitivity ~95%).
• Cryptococcus → India ink positive, cryptococcal antigen (CrAg) latex agglutination most sensitive/specific.
• TB → ADA elevated, AFB smear low yield, CBNAAT (GeneXpert MTB/RIF) rapid, culture is gold standard.

Investigation of choice & the LP–CT question

Stepwise diagnostic flow for suspected bacterial meningitis:

1. Recognise clinically → blood cultures + start empiric antibiotics within ~30–60 min (do not delay).
2. Lumbar puncture for CSF — ideally before antibiotics, but never delay therapy to obtain it.
3. CT head BEFORE LP only if: immunocompromised, history of CNS disease, new-onset seizure, papilloedema, focal neurological deficit, or reduced GCS — to exclude mass lesion/risk of herniation.

Empiric antibiotics first → blood cultures → CT (if indicated) → LP → de-escalate on culture. If LP is delayed, give antibiotics + dexamethasone immediately.

High-yield: The classic MCQ — "next step in patient with focal deficit/papilloedema and suspected meningitis" = start antibiotics + dexamethasone, then CT, then LP. Do NOT do LP first when raised ICP/mass is suspected (risk of coning/uncal herniation).

• Investigation of choice for HSV encephalitis → CSF HSV PCR (and MRI showing temporal lobe involvement). MRI is more sensitive than CT.
• Best imaging for encephalitis → MRI brain — HSV shows asymmetric temporal lobe + insular + cingulate hyperintensity (T2/FLAIR), often haemorrhagic.
• EEG in HSV → PLEDs (periodic lateralised epileptiform discharges) over the temporal region.

Management & drugs of choice

Empiric antibiotic regimen (bacterial meningitis)

Setting	Empiric regimen
Child/adult (immunocompetent)	Ceftriaxone (or cefotaxime) + Vancomycin
>50 yr / immunocompromised / pregnant	Ceftriaxone + Vancomycin + Ampicillin (Listeria cover)
Neonate	Ampicillin + Cefotaxime (± gentamicin)
Post-neurosurgery / penetrating trauma	Vancomycin + Cefepime / Ceftazidime / Meropenem (Pseudomonas cover)
Penicillin allergy	Vancomycin + chloramphenicol; meropenem

Vancomycin is added empirically because of penicillin/cephalosporin-resistant pneumococci.

Definitive (organism-directed):

• Meningococcus / sensitive pneumococcus → penicillin G or ceftriaxone.
• Listeria → ampicillin (+ gentamicin); cotrimoxazole if penicillin-allergic.
• Meningococcal prophylaxis of close contacts → rifampicin, or single-dose ciprofloxacin / ceftriaxone (ceftriaxone preferred in pregnancy).

Dexamethasone — the adjunct rule

High-yield: Give dexamethasone 10 mg IV q6h × 4 days, started BEFORE or WITH the first antibiotic dose. It reduces mortality and hearing loss/neurological sequelae, with the clearest benefit in pneumococcal meningitis (adults) and H. influenzae meningitis (children). Stop it if culture shows it is not pneumococcus (per many guidelines). Giving steroid AFTER antibiotics is ineffective.

Encephalitis

• HSV encephalitis → IV aciclovir (acyclovir) 10 mg/kg q8h × 14–21 days, started empirically on suspicion — do not wait for PCR. Early treatment is the single biggest determinant of outcome.
• Anti-NMDA-R encephalitis → tumour removal + immunotherapy (steroids, IVIG, plasma exchange; second-line rituximab/cyclophosphamide).
• TB meningitis → RIPE (HRZE) for ~9–12 months with adjunctive steroids (proven to reduce mortality), often with prolonged isoniazid/rifampicin continuation.
• Cryptococcal meningitis → Amphotericin B + flucytosine induction → fluconazole consolidation/maintenance; manage raised ICP with repeated therapeutic LPs.

High-yield: "Temporal lobe encephalitis" on MRI = HSV-1 until proven otherwise → start aciclovir immediately. Untreated HSV encephalitis mortality ~70%.

Complications

• Acute: raised ICP → herniation, seizures, SIADH (hyponatraemia), septic shock/DIC, Waterhouse–Friderichsen syndrome (meningococcaemia), subdural effusion/empyema (esp. H. influenzae in children), cerebral venous sinus thrombosis, cranial nerve palsies.
• Vascular: arteritis → cerebral infarction (prominent in TB — basal exudates trap vessels).
• Hydrocephalus: communicating type, classic in TB meningitis (basal exudate obstructs CSF flow).
• Late sequelae: sensorineural hearing loss (commonest permanent sequela, esp. pneumococcal — the main reason for steroids), cognitive impairment, epilepsy, developmental delay in children.

Key differentials

Mimic	Distinguishing clue
Subarachnoid haemorrhage	Thunderclap headache; CT blood; CSF xanthochromia with normal glucose, equal RBCs in all tubes
Brain abscess	Ring-enhancing lesion; LP relatively contraindicated
Migraine / tension headache	No fever, normal CSF
Cerebral malaria	Travel, parasitaemia, normal/near-normal CSF
Metabolic / toxic encephalopathy	Diffuse, no fever, no CSF pleocytosis
Autoimmune (anti-NMDA-R) encephalitis	Psychiatric prodrome, dyskinesias, teratoma, autoantibodies

Traumatic tap vs SAH: in a traumatic tap RBC count falls from tube 1→4 and there is no xanthochromia; in SAH RBCs are uniform across tubes and xanthochromia appears after a few hours (bilirubin).

Recently asked / exam angle

• CSF picture matching — most repeated: identify TB (cobweb clot, low glucose + lymphocytes) vs viral (normal glucose, lymphocytes) vs bacterial (turbid, neutrophils, low glucose).
• Organism by age — neonate (GBS/E. coli/Listeria), young adult (meningococcus), elderly/pregnant (Listeria → add ampicillin).
• CT before LP indications — focal deficit, papilloedema, ↓GCS, seizures, immunocompromise.
• Dexamethasone timing — before/with first antibiotic dose; benefit in pneumococcal meningitis (hearing loss).
• HSV encephalitis — temporal lobe on MRI, PLEDs on EEG, CSF PCR diagnostic, IV aciclovir empirically.
• Waterhouse–Friderichsen — meningococcaemia + bilateral adrenal haemorrhage + DIC.
• Meningococcal chemoprophylaxis — rifampicin / ciprofloxacin / ceftriaxone.
• India ink + CrAg — Cryptococcus in HIV; amphotericin B + flucytosine.
• Mollaret meningitis — recurrent aseptic, HSV-2.
• Anti-NMDA-R encephalitis — young woman + ovarian teratoma + psychiatric + dyskinesia.

Rapid revision

1. Bacterial CSF = turbid, neutrophils, high protein, low glucose, ↑lactate.
2. Viral CSF = clear, lymphocytes, normal glucose — the normal glucose is the giveaway.
3. TB CSF = cobweb (spider-web) clot, xanthochromic, very high protein, low glucose, lymphocytes; ADA↑, CBNAAT.
4. Cryptococcus = India ink + / CrAg most sensitive; very high opening pressure → serial LPs.
5. Listeria at both age extremes (neonate & >50/pregnant/immunocompromised) → add ampicillin (cephalosporins miss it).
6. Empiric adult therapy = ceftriaxone + vancomycin (+ ampicillin if >50/immunocompromised).
7. Dexamethasone before/with first antibiotic dose — biggest benefit in pneumococcal meningitis, prevents hearing loss.
8. CT before LP if focal deficit, papilloedema, seizures, ↓GCS, immunocompromise — else risk herniation; never delay antibiotics.
9. HSV encephalitis = temporal lobe MRI + PLEDs + CSF HSV PCR → IV aciclovir empirically, 14–21 days.
10. Waterhouse–Friderichsen = meningococcaemia + adrenal haemorrhage + DIC + purpura.
11. Kernig/Brudzinski are specific but insensitive; jolt accentuation more sensitive.
12. Commonest permanent sequela of bacterial meningitis = sensorineural hearing loss; TB meningitis classically causes communicating hydrocephalus and basal cranial nerve palsies (III, VI).