Nervous System & Special Senses

Viral and aseptic meningitis: workup and management

Clinical Overview and When to Suspect Viral/Aseptic Meningitis

— Most common cause of community meningitis in the US; ~75,000 cases/year

— Enteroviruses (coxsackie, echovirus) cause 85–90%; peak late summer/early fall

— HSV-2 (recurrent lymphocytic, Mollaret), VZV, HIV (acute seroconversion), arboviruses (West Nile), mumps, LCMV

— Acute headache + fever + neck stiffness, generally less toxic-appearing than bacterial

— Photophobia, malaise, myalgias, sometimes pharyngitis or rash (enteroviral)

— Preserved mental status, no focal neuro deficits, no seizures (those flags push you toward encephalitis or bacterial)

— Recent enteroviral exposure (daycare, summer camp), tick/mosquito exposure, sexual history (HSV-2, acute HIV), travel

Step 3 management: In a stable adult with classic viral meningitis picture, the correct sequence is blood cultures → empiric ceftriaxone + vancomycin (± ampicillin if >50 or immunocompromised) + dexamethasone → LP → reassess based on CSF. Do not withhold empiric antibiotics waiting for the tap if any chance of bacterial disease.

Board pearl: Aseptic meningitis is a diagnosis of exclusion after CSF analysis — the term describes a syndrome, not a confirmed viral etiology. Always document why you've excluded bacterial, fungal, TB, and treatable mimics (HSV, drug-induced, neoplastic) before labeling a case "viral."

Definition: Meningeal inflammation with CSF pleocytosis but negative routine bacterial cultures and Gram stain. "Aseptic" is a CSF profile, not an etiology — it includes viral, partially treated bacterial, fungal, mycobacterial, autoimmune, and drug-induced causes.

Epidemiology:

When to suspect in a Step 3 outpatient or ED encounter:

Why the distinction matters: You cannot reliably distinguish viral from early bacterial meningitis by exam alone — every suspected meningitis needs LP unless contraindicated.

Presentation Patterns and Key History

— Headache (>90%), fever (76–100°F+), neck stiffness, photophobia, nausea/vomiting

— Onset over hours to 1–2 days; less fulminant than bacterial

— Mental status typically preserved — if AMS, seizures, or focal deficits, think encephalitis (HSV-1) rather than pure meningitis

— Enterovirus: summer/fall, GI prodrome, hand-foot-mouth lesions, herpangina, pleurodynia, myocarditis

— HSV-2: young sexually active adult, often with concurrent or prior genital lesions; recurrent episodes = Mollaret meningitis

— Acute HIV: mononucleosis-like illness, maculopapular rash, pharyngitis, lymphadenopathy, recent high-risk exposure 2–4 weeks prior

— VZV: vesicular rash (zoster), but can occur without rash ("zoster sine herpete"); cranial neuropathies

— Arbovirus (West Nile): mosquito exposure, summer, flaccid paralysis or tremor, advanced age

— LCMV: rodent/hamster exposure; pregnant patients → congenital infection risk

— Mumps: parotitis, orchitis, unvaccinated patient

— NSAIDs (ibuprofen — especially in SLE), TMP-SMX, IVIG, OKT3, lamotrigine, intrathecal agents

— Onset hours to days after exposure, resolves with discontinuation

— Petechial/purpuric rash → meningococcal

— Recent neurosurgery, CSF shunt, otitis/sinusitis → bacterial

— Immunocompromised, B-symptoms, weight loss → TB, cryptococcal, lymphomatous

— Subacute (>1 week) course → TB, fungal, partially treated, autoimmune

Key distinction: Meningitis = inflammation without parenchymal dysfunction (alert, no focal deficits, no seizures). Encephalitis = AMS, seizures, focal findings — mandates empiric IV acyclovir while awaiting HSV PCR, regardless of CSF profile.

Board pearl: Recurrent benign lymphocytic meningitis in a young adult = HSV-2 (Mollaret) until proven otherwise; confirm with CSF HSV PCR during an episode and consider suppressive valacyclovir.

Classic syndrome:

Etiology-specific clues:

Drug-induced aseptic meningitis (DIAM):

Red-flag features pushing away from "simple" viral:

Physical Exam Findings (and Hemodynamic Assessment)

— Fever common but may be low-grade or absent (especially elderly, immunocompromised)

— Tachycardia from fever/dehydration; hypotension is unusual in viral and should raise concern for bacterial sepsis or alternate diagnosis

— Hypertension + bradycardia + irregular respirations (Cushing triad) = elevated ICP → urgent imaging before LP

— Nuchal rigidity: resistance to passive neck flexion

— Kernig sign: pain/resistance with knee extension when hip flexed

— Brudzinski sign: involuntary hip/knee flexion with neck flexion

— Jolt accentuation (horizontal head rotation worsening headache): more sensitive but not specific

— Mental status: GCS, orientation, attention (serial 7s) — preserved in pure viral meningitis

— Cranial nerves: VI palsy with elevated ICP; VII or VIII deficits suggest Lyme, basilar TB, or sarcoid

— Motor/sensory/reflexes: focal deficits → think encephalitis, abscess, stroke mimic

— Fundoscopy: papilledema → defer LP, image first

— Vesicles on palms/soles, oropharynx → enterovirus (coxsackie)

— Genital ulcers → HSV-2

— Dermatomal vesicles → VZV

— Petechiae/purpura → meningococcemia (urgent)

— Parotitis → mumps

— Lymphadenopathy, pharyngitis, mucocutaneous ulcers → acute HIV

— Joint effusion → Lyme, viral arthritis

— Hepatosplenomegaly → EBV, CMV, acute HIV

CCS pearl: On the CCS case, document a complete neuro exam including fundoscopy and meningeal signs on initial encounter. Order vitals q1–4h while in the ED, recheck mental status after analgesia/antipyretics, and reassess after CSF results return — case clocks reward serial reassessment.

Board pearl: Absence of classic Kernig/Brudzinski signs does not rule out meningitis — fewer than half of confirmed cases have them. Clinical suspicion alone justifies LP.

Vital signs:

Meningeal signs (low sensitivity, ~30–60%, but high specificity when positive):

Neurologic exam essentials:

Skin and mucosa:

Other:

Diagnostic Workup — Initial Labs and Imaging

— CBC with differential, CMP, glucose (paired with CSF glucose), coagulation studies (before LP), blood cultures × 2, lactate, CRP/procalcitonin

— HIV 4th-gen Ag/Ab test in all suspected aseptic meningitis (acute HIV is a treatable cause)

— Pregnancy test in reproductive-age women

— Immunocompromised state

— History of CNS disease (mass, stroke, focal infection)

— New-onset seizure within 1 week

— Papilledema

— Altered consciousness (GCS <10 or rapid decline)

— Focal neurologic deficit

— Age ≥60 (some guidelines)

— If none present, LP can proceed without CT — and this is the high-yield Step 3 answer

— Patient lateral decubitus for accurate opening pressure (normal 6–25 cm H₂O)

— Tube 1: cell count/diff; Tube 2: glucose, protein; Tube 3: Gram stain, culture; Tube 4: cell count (compare to Tube 1 for traumatic tap) + hold for special studies

— Opening pressure: normal or mildly elevated

— WBC: 10–500/μL, lymphocyte predominance (early enteroviral may be neutrophil-predominant for first 24h — repeat LP shifts to lymphocytic)

— Protein: normal to mildly elevated (<150 mg/dL)

— Glucose: normal (CSF:serum ratio >0.6)

— Gram stain and bacterial culture: negative

— WBC >1000, neutrophil-predominant, protein >200, glucose <40 (ratio <0.4), elevated lactate >3.5 mmol/L

Step 3 management: If CSF is ambiguous (e.g., lymphocytic but low glucose), continue empiric antibiotics and pursue advanced testing (TB, fungal, HSV PCR). Do not stop antibiotics based on a single equivocal profile.

Board pearl: A traumatic tap correction — subtract 1 WBC for every 500–1000 RBCs; recalculate protein as actual minus (1 mg/dL per 1000 RBCs).

Universal initial orders:

When to image (CT head before LP) — IDSA criteria:

Lumbar puncture — opening pressure and tubes:

Typical CSF profile — viral/aseptic:

Contrast with bacterial:

Diagnostic Workup — Advanced and Confirmatory Studies

— Enterovirus PCR: most common positive; >95% sensitivity; positive result allows antibiotic discontinuation and often shortens hospitalization

— HSV-1/2 PCR: mandatory in any encephalitic picture; sensitivity 96–98% after 48h of symptoms

— VZV PCR: especially if rash, cranial neuropathy, or vasculopathy

— CMV, HHV-6, parechovirus (pediatrics)

— HIV: 4th-gen Ag/Ab + HIV RNA viral load if acute seroconversion suspected (antibody may be negative)

— West Nile IgM in CSF: diagnostic for WNV neuroinvasive disease

— Lyme: serum ELISA → Western blot; CSF Lyme antibody index in endemic exposure

— Syphilis: serum RPR + CSF VDRL if positive

— Cryptococcal antigen (CrAg) in CSF and serum if HIV+, transplant, or chronic course

— AFB smear/culture and TB PCR if subacute, basilar imaging changes, exposure

— Persistent symptoms >3–5 days, focal deficits, seizure, AMS

— HSV encephalitis pattern: temporal lobe hyperintensity

— Hydrocephalus, basilar enhancement → TB or fungal

— Leptomeningeal enhancement → neoplastic, infectious, or sarcoid

— Cytology and flow cytometry → carcinomatous/lymphomatous meningitis

— Oligoclonal bands, IgG index → autoimmune/MS workup

— Autoimmune encephalitis panel (anti-NMDA, LGI1) if subacute psych/neuro syndrome

— Repeat LP at 24–48h if initial neutrophilic but bacterial cultures negative — typically shifts lymphocytic in viral

CCS pearl: When CSF returns with lymphocytic pleocytosis, normal glucose, and clinically stable patient → order enterovirus PCR and HSV PCR, and discontinue antibiotics once bacterial cultures are negative at 48h. Advance the clock — discharge planning starts here.

Board pearl: Negative HSV PCR within first 72 hours does not rule out HSV encephalitis — repeat in 3–7 days if clinical suspicion remains; continue acyclovir empirically.

CSF PCR panel (high-yield, often packaged as a meningitis/encephalitis multiplex):

Serologies and ancillary:

Imaging — MRI with contrast indications:

Other CSF studies as indicated:

Risk Stratification and First-Line Management Logic

— Toxic-appearing, hypotensive, purpuric rash, AMS → resuscitate, empiric antibiotics + dexamethasone within 60 min, then LP

— Stable, classic viral picture, no contraindications → LP first acceptable if turnaround <1h, but in practice empiric antibiotics started until CSF results clarify

— Encephalitic features (AMS, seizure, focal deficits) → add IV acyclovir 10 mg/kg q8h until HSV PCR negative

— CSF Gram stain negative, CSF ANC <1000, CSF protein <80, peripheral ANC <10,000, no seizure at/before presentation

— Useful pediatric Step 3 rule; very low risk of bacterial meningitis (<0.1%)

— Most adults require brief hospitalization for IV fluids, antiemetics, analgesia, and CSF result monitoring

— Outpatient management acceptable for stable, well-appearing, immunocompetent adults with confirmed viral etiology, reliable follow-up, and tolerating PO

— Admit if: dehydration, intractable headache/vomiting, immunocompromise, age extremes, diagnostic uncertainty

— Empiric antibiotics: ceftriaxone 2 g IV q12h + vancomycin (cover S. pneumoniae resistance), add ampicillin if >50, pregnant, alcoholic, or immunocompromised (Listeria)

— Dexamethasone 10 mg IV q6h × 4 days before/with first antibiotic dose if pneumococcal suspected; stop if non-bacterial

— Acyclovir if encephalitic features

— Isolation: droplet precautions until meningococcus excluded; standard precautions for most viral

Step 3 management: The single most common Step 3 trap — withholding empiric antibiotics in "looks viral" patients while awaiting LP. Always cover bacterial empirically, then de-escalate. The cost of treating viral with antibiotics for 48h is trivial; the cost of missing bacterial is fatal.

Board pearl: Steroids are only beneficial in pneumococcal meningitis (mortality reduction); stop if CSF/cultures point to viral.

Triage decision tree on arrival:

Bacterial Meningitis Score (children) — low risk if all absent:

Disposition logic for viral meningitis:

Key early decisions:

Pharmacotherapy — First-Line Regimens

— IV fluids (isotonic) for hydration; avoid hypotonic fluids (SIADH risk)

— Analgesia: acetaminophen, NSAIDs (but remember NSAIDs can cause DIAM in SLE)

— Antiemetics: ondansetron 4–8 mg IV q8h PRN

— Antipyretics

— Dark, quiet room for photophobia

— No specific antiviral for enterovirus in adults (pleconaril investigational)

— IV acyclovir 10 mg/kg (ideal body weight) q8h × 14–21 days for encephalitis; meningitis alone 7–10 days

— Monitor renal function — maintain hydration to prevent crystal nephropathy

— Dose adjust in renal impairment (CrCl <50)

— Transition to oral valacyclovir 1 g TID in stable HSV meningitis after improvement

— Suppressive therapy: not routinely recommended after first HSV-2 meningitis episode; consider valacyclovir 500 mg BID for recurrent Mollaret

— IV acyclovir 10–15 mg/kg q8h × 10–14 days

— Add corticosteroids if vasculopathy or cranial neuropathy

— Ganciclovir 5 mg/kg IV q12h ± foscarnet; reduce immunosuppression if possible

— Initiate ART (e.g., bictegravir/TAF/FTC) early; consult ID

— Counsel re: transmission and partner notification

— Discontinue offending agent; supportive care; symptoms resolve within days

— Once CSF culture negative at 48h + viral PCR positive + clinically improving → stop ceftriaxone/vancomycin/ampicillin/dexamethasone

Step 3 management: For an HIV-negative adult with confirmed enteroviral meningitis, stable hemodynamics, tolerating PO, and resolving headache → discharge on supportive care, follow-up in 1–2 weeks. No outpatient antibiotics needed.

Board pearl: IV acyclovir crystal nephropathy is preventable — ensure adequate prehydration and slow infusion over 1 hour; monitor Cr daily.

Viral meningitis — supportive care is the foundation:

HSV meningitis/encephalitis:

VZV meningitis/encephalitis:

CMV (immunocompromised):

Acute HIV with meningitis:

Drug-induced aseptic meningitis:

Empiric bacterial coverage to discontinue:

Procedures and Lumbar Puncture Technique

— Indicated in all suspected meningitis unless contraindicated

— Site: L3–L4 or L4–L5 interspace (below conus medullaris)

— Position: lateral decubitus (for accurate opening pressure) or sitting (easier landmarks, no OP)

— Local anesthesia with 1% lidocaine; sterile technique

— Atraumatic (pencil-point) needle reduces post-LP headache

— Suspected elevated ICP with mass effect (image first)

— Coagulopathy: platelets <50,000, INR >1.4, therapeutic anticoagulation (reverse first if urgent)

— Skin infection over puncture site

— Hemodynamic instability

— Spinal epidural abscess at puncture level

— Warfarin: INR <1.4

— DOACs: hold 48–72h (longer if renal impairment)

— Heparin: hold 4–6h, restart 1h post-LP

— Aspirin alone is generally safe

— >25 cm H₂O = elevated; consider cryptococcal, TB, IIH, mass lesion, venous sinus thrombosis

— In cryptococcal meningitis (HIV), therapeutic LP to drainage <20 cm or 50% reduction is part of management

— Incidence 10–30%; postural worsening

— Treat with bed rest, hydration, caffeine, NSAIDs

— Epidural blood patch for refractory (>72h) or severe cases

— Clinical worsening despite therapy

— Initial neutrophilic picture with negative bacterial cultures (confirm shift to lymphocytic)

— Persistent symptoms >7–10 days

— Suspected TB, fungal, neoplastic (higher-yield repeat sampling)

CCS pearl: Order LP after checking platelets, INR, and (when indicated) head CT — sequence matters on CCS scoring. Document informed consent.

Board pearl: Cisternal or high-cervical LP is rarely needed; if lumbar LP fails after multiple attempts, consult interventional radiology for fluoroscopy-guided LP rather than escalating to riskier approaches.

Lumbar puncture — indications and execution:

Contraindications to LP:

Anticoagulation timing for LP:

Opening pressure interpretation:

Post-LP headache management:

Repeat LP indications:

Special Populations — Elderly and Renal/Hepatic Impairment

— Atypical presentation: confusion or falls may dominate over fever and neck stiffness

— Lower threshold for CT before LP (age, comorbidities, vascular disease)

— Higher risk of bacterial etiologies — Listeria coverage with ampicillin mandatory in empiric regimen

— Polypharmacy review — many medications can cause DIAM (NSAIDs, sulfonamides)

— Delirium screening (CAM) at baseline and serially

— Acyclovir: dose-adjust by CrCl

— CrCl 25–50: 10 mg/kg q12h

— CrCl 10–25: 10 mg/kg q24h

— CrCl <10: 5 mg/kg q24h

— Hemodialysis: dose after HD

— Adequate hydration to prevent crystal nephropathy

— Monitor for acyclovir neurotoxicity (tremor, myoclonus, confusion) — more common in CKD; obtain levels if signs appear

— Ceftriaxone: no renal adjustment, but use cautiously in severe renal + hepatic dysfunction

— Vancomycin: trough-guided dosing, target AUC 400–600

— Avoid nephrotoxins (NSAIDs, IV contrast if possible) during admission

— Acetaminophen: limit to 2 g/day in cirrhosis

— Ceftriaxone: caution in severe biliary disease (biliary sludge)

— Avoid sedating analgesics that worsen encephalopathy

— Document baseline functional status, advance directives

— Discuss code status on admission

— Engage family in shared decision-making for invasive procedures

Step 3 management: In a 78-year-old presenting with confusion and low-grade fever, empirically cover Listeria with ampicillin in addition to ceftriaxone/vancomycin; do not wait for cultures. Listeria has negative Gram stain in 60% and disproportionately affects this population.

Board pearl: Acyclovir-induced neurotoxicity mimics worsening encephalitis — always consider drug toxicity when a CKD patient on acyclovir develops new neuro symptoms; check renal function and consider holding drug or HD.

Elderly (>65) considerations:

Renal impairment:

Hepatic impairment:

Frailty and goals of care:

Special Populations — Pregnancy, Pediatrics, Immunocompromised

— Listeria risk 13–17× higher; ampicillin coverage essential

— Acyclovir is pregnancy category B — use if indicated; benefits outweigh risks in HSV/VZV meningitis

— LP safe in pregnancy; use lateral decubitus for comfort

— LCMV exposure (rodents, hamsters) → severe congenital infection (hydrocephalus, chorioretinitis); counsel pet contact

— HSV-2 meningitis in pregnancy: treat acutely; suppressive valacyclovir from 36 weeks to prevent neonatal transmission if genital lesions

— Avoid doxycycline, fluoroquinolones, TMP-SMX in 1st trimester

— Neonates (<1 month): ampicillin + cefotaxime/gentamicin to cover GBS, E. coli, Listeria, HSV — add acyclovir empirically (neonatal HSV is devastating)

— 1–23 months: ceftriaxone + vancomycin

— Enterovirus and parechovirus dominate viral causes

— Bacterial Meningitis Score useful in children 2 months to 18 years to guide LP and antibiotic decisions

— Mumps and measles resurgence in unvaccinated communities — report to public health

— Dexamethasone in pediatric bacterial meningitis: reduces hearing loss specifically in H. influenzae type b

— Broader differential: cryptococcus, TB, CMV, toxoplasma, lymphoma, PML

— Send CSF cryptococcal antigen, AFB, fungal cultures, CMV PCR, JC virus PCR, cytology

— Lower threshold for MRI with contrast

— On TNF inhibitors → screen for TB, Listeria risk

— Acute HIV can present as aseptic meningitis with negative antibody, positive RNA

— Chronic HIV with low CD4 + headache → cryptococcal until proven otherwise; opening pressure critical

Step 3 management: Pregnant woman with meningitis → ceftriaxone + vancomycin + ampicillin + acyclovir, OB consult, fetal monitoring. Do not delay empiric therapy for imaging or specialist input.

Board pearl: Neonatal HSV meningitis = IV acyclovir 60 mg/kg/day divided q8h × 21 days — higher dose than adults, longer course.

Pregnancy:

Pediatrics:

Immunocompromised (HIV with low CD4, transplant, biologics, chemo):

HIV-specific:

Complications and Adverse Outcomes

— SIADH with hyponatremia — monitor sodium daily; fluid restrict if symptomatic

— Seizures (uncommon in pure meningitis; if present, consider encephalitis)

— Dehydration from vomiting and poor PO intake

— Post-LP headache

— AMS, seizures, focal deficits

— HSV encephalitis: temporal lobe involvement, memory deficits, behavioral changes — mortality 70% untreated, 20–30% treated

— Long-term neurocognitive sequelae common

— Enterovirus 71: brainstem encephalitis, neurogenic pulmonary edema, flaccid paralysis

— West Nile: poliomyelitis-like flaccid paralysis, persistent fatigue/cognitive issues for months

— VZV: vasculopathy → stroke, especially elderly; granulomatous arteritis

— HSV-2 recurrent (Mollaret): chronic recurrent episodes; rarely cognitive sequelae

— HIV: progression to AIDS-related opportunistic CNS infections without ART

— Acyclovir nephrotoxicity, neurotoxicity

— Vancomycin AKI, ototoxicity

— Antibiotic-associated C. difficile

— Catheter-related infections, DVT from immobilization

— Most viral meningitis resolves fully within 7–10 days without sequelae

— Persistent fatigue, headache, concentration difficulties for weeks to months (post-meningitis syndrome)

— Hearing loss (mumps, rarely others) — audiology follow-up

— Cognitive testing if persistent deficits >3 months

Key distinction: Bacterial meningitis carries 10–25% mortality and 30% disability rates; viral meningitis mortality is <1% in immunocompetent adults. This profound prognostic difference is why empiric antibacterial therapy is mandatory until ruled out.

Step 3 management: Hyponatremia in a meningitis patient → check urine osmolality and sodium; if SIADH pattern, fluid restrict to 800–1000 mL/day, avoid hypertonic saline unless seizing or sodium <120.

Acute complications of viral meningitis (generally less severe than bacterial):

Encephalitis overlap (meningoencephalitis):

Specific viral complications:

Iatrogenic complications:

Long-term outcomes:

When to Escalate Care — ICU, Consult, Inpatient Triage

— GCS ≤12 or rapid decline

— Status epilepticus or refractory seizures

— Hemodynamic instability requiring vasopressors

— Respiratory failure or airway protection concerns

— Elevated ICP requiring osmotic therapy or monitoring

— Concern for impending herniation

— IV fluids, analgesia, antiemetics, isolation if needed

— Neuro checks q4h initially

— Repeat sodium, renal function daily

— Tolerating PO, hemodynamically stable

— Confirmed viral etiology (positive PCR, negative cultures)

— Reliable follow-up and support

— No immunocompromise or pregnancy

— Adequate pain control on oral regimen

— Neurology: encephalitic features, seizures, abnormal MRI, suspected autoimmune

— Infectious Disease: immunocompromised host, atypical organism, recurrent meningitis, TB/fungal concern, unclear etiology after standard workup

— Neurosurgery: hydrocephalus, mass effect, possible abscess, shunt-related infection

— OB: pregnant patient

— Public Health: meningococcus, mumps, measles, other reportable diseases

— Lack of neurology/ID consultation at current facility

— No neurosurgical backup for ICP monitoring

— Pediatric patient needing PICU

— Clear documentation of antibiotic timing, CSF results pending, isolation precautions

— SBAR communication for ICU transfer

CCS pearl: On CCS, change location to ICU when GCS drops, seizures occur, or pressors needed. Order continuous EEG if persistent AMS without explanation. Reorder neuro checks q1h in ICU. Advance clock in small increments to capture deterioration.

Step 3 management: A "viral meningitis" patient who develops focal deficits or seizure → immediately add IV acyclovir, obtain MRI brain, repeat LP for HSV PCR, escalate to neurology consult. Do not assume continued benign course.

ICU admission criteria:

Floor admission (most viral meningitis cases):

Outpatient management criteria:

Consultation triggers:

Transfer criteria:

Handoff and CCS workflow:

Key Differentials — Same-Category (Infectious Meningitis)

— S. pneumoniae (most common adult community), N. meningitidis (young adults, dormitories, complement deficiency), Listeria (>50, immunocompromised, pregnant)

— Hyperacute toxic presentation, neutrophilic CSF, low glucose, high protein

— Mortality 10–25%; treat empirically until excluded

— Prior outpatient antibiotics blunt CSF picture — may appear "aseptic"

— Always ask about recent antibiotic use; consider procalcitonin

— Subacute (1–4 weeks), basal meningitis, cranial nerve palsies, hydrocephalus

— CSF: lymphocytic, very high protein (>200), low glucose, elevated ADA

— Empiric RIPE + steroids; mortality high if delayed

— Cryptococcus (HIV, transplant): elevated opening pressure, CrAg positive, treat with liposomal amphotericin + flucytosine → fluconazole

— Coccidioides, Histoplasma in endemic areas

— Neurosyphilis: chronic, dementia, tabes, Argyll Robertson pupils; CSF VDRL

— Lyme neuroborreliosis: cranial neuropathy (esp. CN VII bilateral), radiculitis, lymphocytic CSF

— Eosinophilic meningitis: Angiostrongylus (raw snails), Gnathostoma; CSF eosinophils

— Neurocysticercosis: cystic lesions on imaging, seizures, endemic exposure

— Enteroviruses (most common), HSV-1/2, VZV, HIV acute, mumps, measles, arboviruses (WNV, EEE, Powassan), LCMV, parechoviruses, JC virus (PML — focal)

Board pearl: CSF glucose is the highest-yield single value distinguishing infectious categories — low glucose narrows to bacterial, TB, fungal, or neoplastic; normal glucose suggests viral, drug-induced, or autoimmune.

Key distinction: TB and cryptococcal meningitis can present subacutely with lymphocytic CSF (mimicking viral) but always have low glucose — this single value should redirect workup in any "viral" case lasting >7–10 days.

Bacterial meningitis:

Partially treated bacterial:

Tuberculous meningitis:

Fungal meningitis:

Spirochetal:

Parasitic:

Viral mimics within "aseptic":

Key Differentials — Other-Category Causes

— NSAIDs (esp. ibuprofen in SLE patients), TMP-SMX, IVIG, monoclonal antibodies (OKT3, infliximab), lamotrigine, carbamazepine, isoniazid, allopurinol

— Onset hours to days after exposure; CSF often neutrophilic acutely

— Resolves with discontinuation; rechallenge causes recurrence

— Anti-NMDA receptor encephalitis: young women, psychiatric symptoms, seizures, autonomic instability, ± ovarian teratoma

— Limbic encephalitis (LGI1, CASPR2): memory loss, faciobrachial dystonic seizures

— Behçet disease: oral/genital ulcers, uveitis, recurrent meningoencephalitis

— Sarcoidosis: cranial neuropathies (esp. CN VII), basilar enhancement, hilar adenopathy

— SLE: aseptic meningitis as CNS manifestation; serositis, malar rash

— Vogt-Koyanagi-Harada: meningitis + uveitis + dysacusis + vitiligo

— Breast, lung, melanoma, GI cancers; hematologic malignancies

— Cranial neuropathies, multifocal symptoms, low CSF glucose, positive cytology (sensitivity improves with repeat LPs)

— Subarachnoid hemorrhage — sudden "thunderclap" headache; CSF xanthochromia; CT first

— Cerebral venous sinus thrombosis — headache, seizures, papilledema; MRV diagnostic

— Sterile CSF pleocytosis can occur (HaNDL syndrome — headache with neurologic deficits and CSF lymphocytosis)

— Chemical meningitis after epidural, intrathecal medications, ruptured craniopharyngioma/dermoid

Step 3 management: Adult with recurrent "aseptic meningitis" → review all medications carefully (NSAIDs, TMP-SMX commonly culprit), screen for autoimmune disease (ANA, complement), consider HSV-2 PCR during episode (Mollaret), and obtain CSF cytology and flow cytometry to exclude neoplastic.

Board pearl: SLE patient on ibuprofen who develops meningitis-like illness → think NSAID-induced aseptic meningitis before lupus cerebritis; discontinue NSAID and observe.

Drug-induced aseptic meningitis (DIAM):

Autoimmune and inflammatory:

Neoplastic (carcinomatous/lymphomatous meningitis):

Vascular:

Migraine with meningeal signs:

Post-procedural:

Secondary Prevention, Discharge, and Long-Term Plan

— Afebrile or trending down for ≥24h

— Tolerating PO fluids and oral analgesics

— Headache and neck stiffness improving

— Bacterial cultures negative at 48h

— Viral etiology confirmed or strongly favored

— Stable mental status, no neuro deficits

— Reliable home support and follow-up

— Acetaminophen ± NSAIDs (avoid NSAIDs if DIAM history)

— Antiemetics PRN

— Stool softeners if opioids used

— Continue acyclovir/valacyclovir for HSV/VZV per treatment duration

— Enterovirus: hand hygiene, avoid sharing utensils, no specific vaccine

— Mumps, measles, rubella: MMR vaccination catch-up

— VZV: varicella vaccine in children, shingles vaccine (Shingrix) ≥50 years

— Polio: routine childhood vaccination

— Meningococcus (for bacterial coverage in young adults): MenACWY at 11–12 with booster at 16; MenB for college dorms, asplenia, complement deficiency

— Pneumococcus: PCV15/PCV20 + PPSV23 for adults ≥65 and high-risk

— Influenza: annual

— H. influenzae type b: childhood Hib vaccination

— Start ART immediately for newly diagnosed

— PrEP counseling for partners

— STI screening, partner notification, public health reporting

— Suppressive valacyclovir 500 mg BID — consider after 2+ episodes

— Counsel about transmission risk

— Meningococcus, measles, mumps, polio, certain arboviruses, TB → mandatory reporting

Step 3 management: Patient discharged after enteroviral meningitis → scheduled follow-up at 1–2 weeks with primary care, return precautions (recurrent fever, worsening headache, neuro symptoms), and review of immunization status. Update MMR, Tdap, varicella as needed.

Board pearl: Recurrent meningococcal disease → screen for terminal complement deficiency (C5–C9) and consider MenB vaccination.

Discharge criteria for viral meningitis:

Discharge medications:

Prevention strategies by etiology:

HIV-specific:

Mollaret/recurrent HSV-2:

Public health reporting:

Follow-Up, Monitoring, Rehab, and Counseling

— 1–2 weeks post-discharge: PCP visit — symptom resolution, medication review, return-to-work

— 4–6 weeks: persistent symptoms assessment; neuro/cognitive complaints prompt referral

— 3 months: full recovery expected; if not, formal neuropsychological testing

— Resolution of headache, fever, neck stiffness

— Sodium recheck if SIADH during admission

— Renal function if acyclovir/vancomycin exposure

— Audiology screening if hearing concerns (mumps, post-bacterial)

— Persistent fatigue, headache, concentration/memory issues, mood changes

— Common after viral meningitis, lasting weeks to months

— Reassure most resolve; supportive care, sleep hygiene, graded return to activity

— Refer to neurology if persists >3 months

— Most viral cases need no formal rehab

— Encephalitic cases (HSV) often need cognitive, speech, occupational, physical therapy

— West Nile poliomyelitis-like presentations need extensive neurorehab

— Resume normal activities as tolerated, generally within 1–2 weeks

— Return to school/work when afebrile, energy adequate, headache controlled

— Athletes: gradual return, no contact sports until cleared

— Driving: hold if seizures occurred (state-specific reporting requirements)

— Transmission: enterovirus fecal-oral, droplet — hand hygiene

— HSV-2: sexual transmission, suppressive therapy options, partner notification

— Acute HIV: linkage to care, partner notification, treatment as prevention

— Vaccination updates

— Stress reduction, sleep, gradual reconditioning

— Ensure insurance coverage for ongoing antivirals (valacyclovir often requires prior auth for suppression)

— Care coordination with ID and neurology as needed

Step 3 management: Patient returning at 6 weeks with persistent fatigue and headache after enteroviral meningitis → reassure, optimize sleep, graded exercise, address mood, avoid over-investigation if exam normal; consider neuro referral only if focal findings or progression.

Board pearl: New-onset seizure during meningitis episode warrants driving restriction per state DMV regulations (commonly 6 months seizure-free) — counsel and document.

Outpatient follow-up cadence:

Monitoring parameters:

Post-meningitis syndrome:

Rehabilitation considerations:

Return-to-activity counseling:

Counseling topics:

Health systems:

Ethical, Legal, and Patient Safety Considerations

— Document risks: bleeding, infection, post-LP headache, nerve injury, herniation (rare)

— Capacity assessment in altered patients — proceed under emergency exception if life-threatening and decision-maker unreachable

— Surrogate decision-maker per state hierarchy if patient incapacitated

— Meningococcal disease: report to public health within 24h; post-exposure prophylaxis for close contacts (ciprofloxacin, rifampin, or ceftriaxone)

— Measles, mumps: contact tracing, isolation

— TB: directly observed therapy, contact investigation

— HIV: state-specific reporting; partner notification programs

— Arboviruses: West Nile reportable in most states

— HIV status protected under specific state laws; disclosure rules vary

— Partner notification: many jurisdictions have "duty to warn" but allow anonymous public health notification

— Antibiotic timing: door-to-antibiotic <60 min for suspected bacterial meningitis is a quality metric

— Medication reconciliation to identify DIAM (NSAIDs, TMP-SMX)

— Verify allergies before empiric regimen (true penicillin allergy → meropenem; reported allergy → consider skin testing or ceftriaxone if reaction was non-anaphylactic)

— LP site verification and time-out before procedure

— Anticoagulation hold documented and communicated

— Pending CSF results at discharge — designate accountable provider for follow-up

— Antibiotic discontinuation plan clearly communicated to outpatient team

— Critical results notification system for delayed cultures

— Cluster of viral meningitis → notify public health, investigate exposure source (daycare, water source)

— Vaccine-preventable outbreaks (mumps, measles) require school/workplace coordination

— Pregnant patient refusing acyclovir for HSV → respect autonomy after informed counseling; document

— Pediatric patient with unvaccinated status → discuss catch-up, do not delay treatment

Step 3 management: College freshman with meningococcal meningitis → immediate public health notification, post-exposure prophylaxis for close contacts (roommates, intimate partners) with single-dose ciprofloxacin 500 mg PO, and notify the dormitory and student health.

Board pearl: Pending HIV test result at discharge in a meningitis patient — establish a closed-loop result notification with PCP and patient contact information; missed acute HIV diagnosis is a high-risk transition.

Informed consent for LP:

Mandatory reporting:

Confidentiality:

Patient safety pearls:

Transitions of care risks:

Public health and outbreak:

Ethical edge cases:

High-Yield Associations and Rapid-Fire Clinical Facts

— Summer/fall: enteroviruses, arboviruses (West Nile)

— Winter/spring: mumps (rare with vaccination), LCMV, influenza-associated

— Mosquitoes → West Nile, EEE, Powassan

— Ticks → Lyme, Powassan

— Rodents/hamsters → LCMV

— Raw snails → Angiostrongylus (eosinophilic)

— Daycare/swimming pools → enterovirus

— College dormitory → meningococcus, mumps

— Sexual contact → HSV-2, acute HIV, syphilis

— Lymphocytic + normal glucose → viral, DIAM, partially treated bacterial, early

— Lymphocytic + low glucose → TB, fungal, neoplastic, listeria (sometimes)

— Neutrophilic + low glucose → bacterial

— Neutrophilic + normal glucose → early viral (enterovirus, WNV), DIAM

— Eosinophilic → parasitic, fungal (coccidio), drug

— Mollaret meningitis → HSV-2

— Temporal lobe MRI lesion → HSV-1 encephalitis

— Basilar meningitis + cranial nerves → TB, sarcoid, fungal

— Hydrocephalus + immigrant → TB

— Hyponatremia + meningitis → SIADH (especially TB)

— Flaccid paralysis + meningitis → West Nile, enterovirus 71, polio

— Stroke + recent zoster → VZV vasculopathy

— Hand-foot-mouth + meningitis → coxsackie A

— Parotitis + meningitis → mumps

— Vesicles + ataxia + immunocompromised → VZV

— NSAIDs, Sulfas (TMP-SMX), Allopurinol, IVIG, Dilantin/lamotrigine, TNF inhibitors, INH, Monoclonals, Etanercept

— <1 month: ampicillin + cefotaxime + acyclovir

— 1 month–50 years: ceftriaxone + vancomycin

— >50, pregnant, immunocompromised: add ampicillin

— Add acyclovir if encephalitic features

— Add dexamethasone if suspected pneumococcal

Board pearl: West Nile virus is the leading cause of arboviral neuroinvasive disease in the US — suspect in late summer with mosquito exposure, especially in older adults; diagnose with CSF IgM.

Etiology by season:

Etiology by exposure:

CSF pattern cheat sheet:

Classic associations:

Drug culprits for DIAM mnemonic — "NSAID-TIME":

Empiric regimen recall:

Board Question Stem Patterns

— "20-year-old in August with 2 days of headache, fever, photophobia, neck stiffness; alert; CSF: 200 WBC (80% lymphs), protein 60, glucose 65 (serum 90)"

— Best next step: enterovirol PCR, supportive care, discontinue empiric antibiotics at 48h if cultures negative

— "65-year-old with headache, fever, new focal weakness"

— Best next step: head CT before LP, blood cultures, empiric antibiotics + dexamethasone immediately (don't wait for CT)

— "30-year-old with fever, confusion, aphasia, seizure; MRI shows temporal lobe enhancement"

— Best next step: IV acyclovir empirically, CSF HSV PCR, EEG

— "28-year-old with 3rd episode of self-limited lymphocytic meningitis over 2 years"

— Diagnosis: Mollaret (HSV-2) → CSF HSV-2 PCR; consider suppressive valacyclovir

— "72-year-old with confusion, fever, neck stiffness; CSF: 500 WBC (mixed), low glucose, Gram stain negative"

— Best regimen: ceftriaxone + vancomycin + ampicillin + dexamethasone

— "SLE patient on ibuprofen develops headache, fever, neck stiffness; LP lymphocytic, normal glucose, all cultures and PCRs negative; resolves over 3 days"

— Diagnosis: NSAID-induced aseptic meningitis; avoid NSAIDs in future

— "25-year-old MSM with mononucleosis-like illness 3 weeks after high-risk encounter, now with headache, neck stiffness; HIV antibody negative"

— Best test: HIV RNA viral load (or 4th-gen Ag/Ab); initiate ART

— "70-year-old farmer in August with fever, headache, flaccid arm weakness"

— Best test: CSF West Nile IgM

— "HIV patient CD4 30, subacute headache 3 weeks, opening pressure 35"

— Best test: CSF cryptococcal antigen; treat amphotericin + flucytosine; serial therapeutic LPs

— "College student with meningococcal meningitis; roommate exposure"

— Best step: ciprofloxacin 500 mg PO × 1 for close contacts; public health notification

Step 3 management: When the stem says "best next step" in a stable viral-appearing meningitis patient with already-negative CSF for bacteria and positive enterovirus PCR — answer is almost always discontinue antibiotics and provide supportive care/discharge planning, not additional testing.

Board pearl: If acyclovir is in the answer choices and any feature of encephalitis is present, it's almost always the right answer.

Stem 1 — Classic enteroviral:

Stem 2 — Need for CT before LP:

Stem 3 — HSV encephalitis:

Stem 4 — Recurrent benign meningitis:

Stem 5 — Listeria in elderly:

Stem 6 — Drug-induced:

Stem 7 — Acute HIV:

Stem 8 — West Nile:

Stem 9 — Cryptococcal:

Stem 10 — Meningococcal contacts:

One-Line Recap

Viral and aseptic meningitis is a CSF-defined syndrome that demands empiric bacterial coverage and HSV consideration until proven otherwise — only after ruling out treatable mimics through LP, PCR, and clinical course can supportive care safely become the answer.

— Suspected meningitis → blood cultures + empiric ceftriaxone/vancomycin (±ampicillin, ±acyclovir, ±dexamethasone) → LP (CT first only if focal deficit, papilledema, AMS, immunocompromise, seizure, age >60)

— Classic viral CSF: lymphocytic pleocytosis, normal glucose, mildly elevated protein, negative Gram stain

— Always send HIV testing and HSV PCR; add enterovirus PCR in seasonal cases

— Most viral meningitis = supportive care, discontinue antibiotics at 48h if cultures negative and viral confirmed

— HSV/VZV → IV acyclovir; dose-adjust for renal function and hydrate to prevent crystal nephropathy

— Treat the patient, not just the CSF — recurrent or atypical cases need expanded workup (TB, fungal, autoimmune, neoplastic, drug-induced)

— Admit for IV hydration, observation, pending cultures; outpatient management appropriate for confirmed viral, stable adults

— ICU for encephalitic features, seizures, instability

— Public health reporting for meningococcus, mumps, measles, HIV, West Nile

— Withholding empiric antibiotics in "looks viral" cases — never

— Missing acute HIV in young adult with aseptic picture

— Missing HSV-2 (Mollaret) in recurrent meningitis

— Forgetting Listeria coverage in >50, pregnant, immunocompromised

— Failing to consider DIAM in SLE patients on NSAIDs

Board pearl: Master three numbers — CSF glucose ratio (<0.4 bacterial), opening pressure (>25 cryptococcal/TB), and door-to-antibiotic time (<60 min) — and you've captured the spine of every meningitis vignette.

Diagnosis core:

Treatment core:

Disposition core:

Step 3 traps to avoid: