Neuroinfectious Disease
Neuroinfectious Disease
What You'll Learn
- Bacterial meningitis: do NOT delay antibiotics for imaging — give vancomycin + ceftriaxone/cefotaxime + dexamethasone empirically; ADD ampicillin if age ≥50, pregnant, or immunocompromised (Listeria coverage); dexamethasone BEFORE or WITH first antibiotic dose reduces mortality in S. pneumoniae
- HSV encephalitis: temporal lobe + fever + seizures = start IV acyclovir immediately — do NOT wait for PCR; most common sporadic fatal encephalitis
- Brain abscess: central restricted diffusion is characteristic — pyogenic abscesses usually restrict; necrotic tumors usually do not. Not pathognomonic: some metastases / high-cellularity tumors can restrict.
- HIV neurology: Toxoplasmosis (ring-enhancing, multiple, basal ganglia) vs. CNS lymphoma (single, periventricular, EBV+) — empiric toxo treatment first; biopsy if no response
- PML: multifocal white matter lesions + NO mass effect + immunosuppressed = JC virus; natalizumab risk stratification by JCV antibody index
- Neurosyphilis: Argyll Robertson pupil (accommodates but does NOT react to light) is pathognomonic; CSF VDRL is specific but NOT sensitive
- CJD: rapidly progressive dementia + myoclonus + cortical ribboning on DWI = sCJD; RT-QuIC is now the most sensitive and specific CSF test
HighYield Pearls
- Bacterial meningitis empiric therapy: vancomycin + ceftriaxone for all adults; ADD ampicillin if ≥50, immunocompromised, or pregnant (Listeria); dexamethasone BEFORE or WITH first antibiotic dose for suspected pneumococcal — do NOT delay antibiotics for CT/LP
- HSV-1 encephalitis: fever + AMS + focal seizures + TEMPORAL/INSULAR/ORBITOFRONTAL T2/FLAIR/DWI hyperintensity (often bilateral asymmetric, gyral enhancement) → start IV acyclovir 10 mg/kg q8h empirically; CSF lymphocytic with RBCs; PCR confirms; ≥50% develop epilepsy; anti-NMDAR encephalitis can follow
- TB meningitis: subacute BASAL meningitis + cranial neuropathies (III, VI) + hydrocephalus + basal vasculitis infarcts; CSF lymphocytic + very low glucose + very high protein; RIPE × 12 mo + ADJUNCTIVE DEXAMETHASONE (improves survival)
- Cryptococcal meningitis (HIV CD4 <100): amphotericin B + flucytosine induction → fluconazole consolidation/maintenance; SERIAL LPs (NOT shunt initially) for elevated ICP — ICP management drives survival
- Toxoplasmosis vs PCNSL in HIV: toxo = MULTIPLE ring-enhancing lesions at basal ganglia + GW junction, serum IgG+ → empiric pyrimethamine + sulfadiazine; PCNSL = SINGLE periventricular, EBV+, thallium SPECT/PET avid — biopsy if no response to toxo therapy in 2 weeks
- Neurocysticercosis: seizures + Mexico/Central America exposure + cysts at GW junction. 1–2 viable cysts: albendazole monotherapy × 10–14 d + corticosteroids started BEFORE antiparasitic. >2 viable cysts: albendazole + praziquantel + steroids. Single enhancing lesion: albendazole + steroids (NOT steroids alone). Calcified lesions: symptomatic/seizure management only — no antiparasitic
- PML: JC virus reactivation in HIV / natalizumab / rituximab / ocrelizumab / fingolimod; multifocal SUBCORTICAL T2 hyperintensities, NO mass effect, NO enhancement; CSF JCV PCR; treat by REVERSING immunosuppression; watch for IRIS
- Neurosyphilis: Argyll Robertson pupil (accommodates but does NOT react) + tabes dorsalis + general paresis; CSF VDRL specific but NOT sensitive; treat with IV penicillin G × 14 days — oral/IM benzathine does NOT penetrate CNS
- Sporadic CJD: RPD + myoclonus + cerebellar/visual/pyramidal; MRI DWI cortical ribboning + basal ganglia (pulvinar sign in variant CJD); EEG periodic sharp wave complexes (1 Hz); CSF RT-QuIC (most sensitive/specific) > 14-3-3 + tau; fatal, no treatment
- Lyme neuroborreliosis: BILATERAL CN VII palsy + painful radiculopathies + lymphocytic meningitis; ELISA + Western blot; CSF Lyme antibody index. Per 2020 AAN/ACR/IDSA: meningitis, cranial neuritis, and radiculoneuritis can be treated with oral doxycycline OR IV ceftriaxone/cefotaxime/penicillin G × 14–21 days; reserve IV therapy for parenchymal brain/spinal cord involvement or inability to take oral therapy.
🔍 Quick ReferenceClinical / CSF · Imaging / pathology · Treatment
Clinical / CSF
- Fever + meningismus + AMS triad + photophobia → bacterial meningitis
- Argyll Robertson pupil (accommodates, does NOT react to light) → neurosyphilis (tabes dorsalis)
- Bilateral CN VII palsy + tick exposure + erythema migrans → Lyme neuroborreliosis
- Fever + focal seizures + behavioral change + temporal lobe signs → HSV-1 encephalitis
- Fever + flaccid asymmetric paralysis (polio-like) + parkinsonism → West Nile virus
- HZ ophthalmicus → delayed contralateral hemiparesis → VZV vasculopathy
- CSF lymphocytic + very low glucose + very high protein, subacute course → TB or fungal meningitis
- CSF India ink + cryptococcal antigen + HIV CD4 <100 → cryptococcal meningitis
- CSF RT-QuIC positive + 14-3-3 + tau elevated → sporadic CJD
- Rapidly progressive dementia + myoclonus + startle → CJD
- CSF VDRL reactive (specific not sensitive) → neurosyphilis
- Tabes dorsalis: sensory ataxia + lancinating pains + dorsal column atrophy → tertiary syphilis
Imaging / pathology
- Bilateral asymmetric temporal + insular + orbitofrontal T2/FLAIR/DWI hyperintensity with gyral enhancement → HSV-1 encephalitis
- Basal meningeal enhancement + hydrocephalus + basal ganglia infarcts → TB meningitis
- Multiple ring-enhancing lesions at basal ganglia + GW junction in HIV → toxoplasmosis
- Single periventricular homogeneous-enhancing lesion in HIV, thallium-avid → PCNSL (EBV-driven)
- Ring-enhancing lesion with restricted diffusion in CENTER + dark T2 capsule → pyogenic brain abscess
- “Star of Jerusalem” scolex within cyst at GW junction; multistage (vesicular → colloidal → granular → calcified) → neurocysticercosis
- Multifocal subcortical white matter T2 hyperintensities, NO mass effect, NO enhancement → PML (JC virus)
- DWI cortical ribboning + basal ganglia hyperintensity → sporadic CJD
- Pulvinar sign (bilateral posterior thalamic DWI hyperintensity) → variant CJD
- EEG periodic sharp wave complexes at ~1 Hz → sporadic CJD
- Spongiform vacuolation + prion protein deposition on biopsy → CJD
- Monophasic large confluent post-viral demyelinating lesions in child → ADEM
Treatment / pearls
- Vancomycin + ceftriaxone + dexamethasone BEFORE/WITH first dose → empiric bacterial meningitis (suspected pneumococcal)
- Add ampicillin for age ≥50 / immunocompromised / pregnant → Listeria coverage
- IV acyclovir 10 mg/kg q8h × 14–21 days, do NOT wait for PCR → HSV encephalitis
- RIPE × 12 months + adjunctive dexamethasone → TB meningitis
- Amphotericin B + flucytosine induction → fluconazole + SERIAL LPs for ICP → cryptococcal meningitis in HIV
- Pyrimethamine + sulfadiazine + leucovorin (empiric, then reassess at 2 wk) → CNS toxoplasmosis
- Albendazole + steroids (steroids BEFORE antiparasitic); add praziquantel if >2 viable cysts → neurocysticercosis (calcified lesions → symptomatic only)
- IV penicillin G × 14 days (oral/IM does NOT penetrate CNS) → neurosyphilis
- Oral doxycycline OR IV ceftriaxone/cefotaxime/penicillin G × 14–21 days → Lyme meningitis / cranial neuritis / radiculoneuritis (2020 AAN/ACR/IDSA); reserve IV therapy for parenchymal brain/cord disease
- Reverse immunosuppression (stop natalizumab, restart ART) → PML — watch for IRIS
- Rifampin or ciprofloxacin or ceftriaxone for close contacts → N. meningitidis chemoprophylaxis
- Steroids/IVIG for monophasic post-viral demyelination → ADEM
Bacterial Meningitis
CSF Profiles Comparison
| Parameter | Bacterial | Viral | TB/Fungal | Carcinomatous |
|---|---|---|---|---|
| WBC | 1,000–10,000+ (PMNs) | 10–500 (lymphocytes) | 100–500 (lymphocytes) | 10–200 (lymphocytes) |
| Protein | ↑↑ (100–500+) | Normal–mildly ↑ | ↑↑↑ (100–500+) | ↑↑ (50–200+) |
| Glucose | ↓↓ (<40 or <2/3 serum) | Normal | ↓↓↓ (often <20) | ↓↓ |
| Opening pressure | ↑↑ (200–500+) | Normal–mildly ↑ | ↑↑ | ↑ |
| Special tests | Gram stain, culture, latex agglutination | PCR (enterovirus, HSV) | AFB smear/culture, India ink, CrAg | Cytology (×3 LPs), flow cytometry |
Clinical Pearl
- PMN-predominant CSF + low glucose = bacterial until proven otherwise
- Early viral meningitis can have PMN predominance — repeat LP in 6–12 hours shows lymphocytic shift
- TB and fungal can initially show mixed or PMN-predominant cells
Empiric Antibiotic Therapy by Age
| Age Group | Common Organisms | Empiric Regimen |
|---|---|---|
| Neonates (<1 month) | GBS, E. coli, Listeria | Ampicillin + gentamicin + cefotaxime |
| Infants/Children (1 mo–18 yr) | S. pneumoniae, N. meningitidis, H. influenzae | Ceftriaxone + vancomycin + dexamethasone |
| Adults (18–50 yr) | S. pneumoniae, N. meningitidis | Ceftriaxone 2 g IV q12h + vancomycin 15–20 mg/kg IV q8–12h (target trough 15–20 mcg/mL) + dexamethasone 0.15 mg/kg IV q6h × 4 days |
| Adults ≥50 yr / Immunocompromised / Pregnant | S. pneumoniae, Listeria, gram-negatives | Above regimen + ampicillin 2 g IV q4h for Listeria coverage (cephalosporins do NOT cover Listeria) |
| Hospital-acquired / post-neurosurgical / penetrating trauma / CSF shunt | S. aureus (incl. MRSA), Pseudomonas, gram-negatives, coag-neg Staph | Vancomycin 15–20 mg/kg IV q8–12h + cefepime 2 g IV q8h OR meropenem 2 g IV q8h (covers Pseudomonas + MRSA + gram-negatives) |
Dexamethasone in Bacterial Meningitis
- Timing: give BEFORE or WITH the first antibiotic dose — NOT after
- Dose: 0.15 mg/kg IV q6h × 4 days
- Proven benefit: primarily for S. pneumoniae — reduces hearing loss and mortality
- Mechanism: decreases subarachnoid inflammation → less vasogenic edema and cochlear damage
- Discontinue if organism is NOT S. pneumoniae (some experts continue for H. influenzae in children)
Chemoprophylaxis
| Organism | Prophylaxis Indicated | Regimen |
|---|---|---|
| N. meningitidis | Close contacts (household, daycare, direct exposure to secretions) | Rifampin × 2 days OR ciprofloxacin × 1 dose OR ceftriaxone IM × 1 dose |
| H. influenzae type b | Household contacts with unvaccinated children <4 yr | Rifampin × 4 days |
| S. pneumoniae | None (no prophylaxis for contacts) | — |
Complications of Bacterial Meningitis
- SIADH → hyponatremia (monitor sodium closely)
- Hydrocephalus — communicating (inflammatory adhesions) or obstructive
- Subdural empyema/effusion
- Cerebral venous sinus thrombosis
- Sensorineural hearing loss — most common long-term sequela; test audiometry in all survivors
- Seizures — occur in ~30% of bacterial meningitis. Status epilepticus in CNS infection: treat per status protocol — levetiracetam 60 mg/kg IV load or fosphenytoin 20 PE/kg; consider cEEG monitoring since patients are encephalopathic and seizures may be subclinical (nonconvulsive status epilepticus is common)
- Cerebral infarction — vasculitis/vasospasm of perforating arteries
💎 Board Pearl
- LP contraindications (focal neuro deficit, papilledema, altered consciousness, immunocompromised, seizures) — get CT first BUT do NOT delay antibiotics; give empiric treatment BEFORE imaging
- Add ampicillin for Listeria in neonates, elderly (>50), pregnant, and immunocompromised — cephalosporins do NOT cover Listeria
- Waterhouse-Friderichsen syndrome: bilateral adrenal hemorrhage from N. meningitidis sepsis → DIC + shock + purpura fulminans
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