Viral meningitis and viral encephalitis are classic USMLE “look-alikes”: both can present with fever + headache, but one is usually benign and self-limited (meningitis) while the other can be rapidly devastating (encephalitis). The test loves to see whether you can (1) localize inflammation to meninges vs brain parenchyma, (2) interpret CSF patterns, and (3) recognize the high-yield viral culprits—especially HSV-1 temporal lobe encephalitis.
Big picture: definitions (don’t mix these up)
Viral meningitis
- Inflammation of the leptomeninges (pia + arachnoid)
- Presents with meningeal signs: headache, photophobia, nuchal rigidity
- Normal mental status (or only mild lethargy)
- Usually self-limited in immunocompetent patients
Viral encephalitis
- Inflammation of brain parenchyma
- Adds altered mental status, seizures, focal neurologic deficits
- Higher morbidity/mortality; requires urgent workup and often empiric acyclovir
Meningoencephalitis
- Overlap syndrome: meningeal signs plus parenchymal findings.
High-yield rule:
If there’s confusion, personality change, seizures, aphasia, focal deficits → think encephalitis until proven otherwise.
Etiology: the viruses you’re expected to know
Most common causes of viral meningitis (USMLE favorites)
- Enteroviruses (Coxsackie, Echovirus) — most common overall
- HSV-2 — recurrent “Mollaret meningitis” (benign recurrent lymphocytic meningitis)
- VZV
- HIV (acute retroviral syndrome)
- Mumps (less common with vaccination)
High-yield causes of viral encephalitis
- HSV-1 — most common sporadic fatal encephalitis in the US
- West Nile virus — tremor, parkinsonism, flaccid paralysis (anterior horn involvement)
- VZV
- Rabies — hydrophobia, aerophobia, autonomic instability
- Arboviruses (EEE/WEE/SLE), Japanese encephalitis
- CMV (especially AIDS/transplant): ventriculoencephalitis, periventricular disease
Pathophysiology (what’s actually happening)
Viral meningitis: “meningeal irritation”
- Viruses typically reach CNS via:
- Hematogenous spread (enteroviruses, HIV)
- Neuronal spread (HSV, rabies)
- Infection triggers lymphocytic inflammation of CSF/meninges → pain-sensitive meningeal irritation → headache, photophobia, neck stiffness.
Viral encephalitis: “parenchymal injury”
- Viral replication in neurons/glia → edema, necrosis, and inflammatory damage.
- HSV-1 encephalitis:
- Predilection for temporal lobes (often bilateral but asymmetric)
- Causes hemorrhagic necrosis
- Explains classic symptoms:
- Memory impairment, personality changes
- Aphasia (dominant temporal)
- Seizures
- Hallucinations
Clinical presentation: what to look for on vignettes
Viral meningitis (typical)
- Fever
- Headache
- Photophobia
- Nuchal rigidity
- Nausea/vomiting
- Usually no focal neuro deficits
- Mental status: typically normal
Viral encephalitis (red flags)
- Fever + headache plus:
- Altered mental status (confusion, lethargy, agitation)
- Seizures
- Focal neuro deficits (aphasia, hemiparesis)
- Behavioral/personality changes (limbic/temporal involvement)
High-yield associations
- HSV-1 encephalitis: temporal lobe signs, RBCs in CSF, hemorrhagic MRI changes
- West Nile: older adults, outdoor exposure/mosquitoes, movement disorders, acute flaccid paralysis
- Rabies: animal bite, hydrophobia, agitation, hypersalivation → coma
- VZV: dermatomal rash + neuro symptoms; can cause vasculopathy/stroke-like deficits
Diagnosis: the Step-wise approach that wins points
Step 1: Decide if you need CT before LP
Get head CT prior to lumbar puncture if risk of herniation:
- Focal neurologic deficit
- New-onset seizure
- Papilledema
- Immunocompromised state
- Altered mental status
If no red flags: LP can be done promptly.
Step 2: Interpret CSF (viral vs bacterial is a core USMLE skill)
| CSF Finding | Viral Meningitis/Encephalitis | Bacterial Meningitis (contrast) |
|---|---|---|
| Opening pressure | Normal to mildly ↑ | ↑ |
| WBC | ↑ (typically 50–1000) | ↑ (often 1000–5000) |
| Differential | Lymphocytic predominance | Neutrophilic predominance |
| Protein | Normal to ↑ | ↑↑ |
| Glucose | Normal (usually) | Low |
| Gram stain | Negative | Often positive |
| PCR | Often positive (HSV, enterovirus) | N/A |
Two high-yield caveats:
- Early viral meningitis can show neutrophil predominance briefly—don’t get tricked.
- HSV encephalitis can show RBCs in CSF due to hemorrhagic necrosis.
Step 3: Order the “money tests”
- CSF PCR:
- HSV PCR (high sensitivity/specificity)
- Enterovirus PCR
- VZV PCR in appropriate setting
- MRI brain (encephalitis > meningitis):
- HSV-1: temporal lobe hyperintensity ± hemorrhage
- EEG (sometimes tested):
- HSV can show temporal periodic discharges (supportive, not definitive)
Treatment: what you do before you know the answer
Viral meningitis (most cases)
- Supportive care
- Fluids, antipyretics, analgesia
- Observation if stable
- Targeted antivirals only in select situations:
- Acyclovir for suspected/confirmed VZV (and sometimes HSV)
- HIV-associated conditions managed per HIV guidelines
Viral encephalitis (treat first, confirm later)
- Empiric IV acyclovir immediately if encephalitis suspected
- Rationale: missing HSV encephalitis is catastrophic and acyclovir is beneficial.
- Supportive + ICU as needed:
- Airway protection
- Seizure control (e.g., levetiracetam)
- Manage intracranial pressure if severe edema
Key pharmacology pearl (USMLE-style)
- Acyclovir adverse effect: crystal nephropathy
- Prevention: IV hydration, slow infusion; monitor renal function.
Prognosis (what the exam wants you to infer)
- Viral meningitis: usually good outcomes, especially enteroviral.
- HSV encephalitis:
- High mortality untreated
- Improved survival with early acyclovir, but neuro deficits can persist.
- West Nile neuroinvasive disease: prolonged recovery; older/immunocompromised worse.
High-yield “bugs-to-syndrome” map (memorize this)
- Enteroviruses → most common viral meningitis, summer/early fall outbreaks
- HSV-2 → recurrent lymphocytic meningitis (Mollaret)
- HSV-1 → temporal lobe encephalitis, hemorrhagic necrosis, RBCs in CSF
- VZV → meningitis/encephalitis ± rash; vasculopathy
- CMV (AIDS/transplant) → encephalitis/ventriculitis, periventricular involvement
- Rabies → hydrophobia, autonomic instability; Negri bodies (classically)
- West Nile → encephalitis + movement disorder; acute flaccid paralysis
Rapid differentiation: meningitis vs encephalitis (test-day checklist)
Think meningitis when:
- Headache + neck stiffness + photophobia
- No focal deficits
- No major altered mental status
Think encephalitis when:
- Any altered mental status
- Seizures
- Focal deficits
- Behavioral/personality changes
→ Start acyclovir
First Aid cross-references (by concept)
Page numbers vary by edition, so use these as “where to look” anchors in First Aid for the USMLE Step 1:
- CSF patterns (viral vs bacterial vs fungal/TB)
- Look under CNS infections and meningitis—CSF findings tables.
- HSV encephalitis
- Under Herpesviruses and CNS infections: temporal lobe involvement, hemorrhagic features.
- Enteroviruses
- Under Picornaviruses: aseptic meningitis association.
- Rabies
- Under Rhabdoviruses: hydrophobia, Negri bodies.
- West Nile / arboviruses
- Under Flaviviruses/arboviruses: encephalitis associations.
- Acyclovir toxicity
- Under antivirals: crystal nephropathy.
USMLE-style mini-vignettes (pattern recognition)
-
College student, summer, fever + headache + neck stiffness, normal mental status, CSF lymphocytes, normal glucose → Enteroviral meningitis, supportive care.
-
Fever + headache + new seizures, confusion, MRI temporal lobe, CSF RBCs → HSV-1 encephalitis, start IV acyclovir now.
-
Older adult, mosquito exposure, fever + confusion + tremor/parkinsonism ± flaccid weakness → West Nile neuroinvasive disease.
Take-home high-yield summary
- Viral meningitis: meningeal signs, normal glucose, lymphocytes, usually supportive care.
- Viral encephalitis: altered mental status/seizures/focal deficits; get MRI + CSF PCR; empiric IV acyclovir for suspected HSV.
- HSV-1: temporal lobe, hemorrhagic necrosis, RBCs in CSF—don’t miss it.