Aseptic Meningitis

Definition

• Adams and Victor's Principles of Neurology, 12e

Epidemiology

• Annual incidence: ~20 cases per 100,000 population
• Predominantly a disease of children and young adults
• Enteroviral cases peak in August–September; mumps peaks in late winter–spring
• Adams and Victor's Principles of Neurology, 12e

Etiology

Infectious (Viral — ~80% of identifiable cases)

A specific viral cause cannot be established in ≥ 1/3 of presumed viral cases even with conventional testing.

Non-viral Infectious

• Partially treated bacterial meningitis
• Mycobacterium tuberculosis
• Cryptococcus, other fungi
• Syphilis (Treponema pallidum)
• Lyme disease (Borrelia burgdorferi)
• Mycoplasma, rickettsiae (difficult to culture)
• Brucella, Nocardia, HIV

Non-infectious (Important Causes)

Key pearl (Goldman-Cecil): Hypoglycorrhachia (low CSF glucose) is a feature of few non-infectious aseptic meningitides; when present, it suggests malignancy or sarcoidosis.

Clinical Features

• Erythematous papulomacular rash (head/neck or generalized): echovirus, Coxsackievirus
• Herpangina (vesiculoulcerative oral lesions): group A Coxsackievirus
• Classic childhood exanthems: varicella, rubella, mumps

CSF Findings

Early caveat: In the first hours, CSF may show a neutrophilic predominance — repeat LP in 4–6 hours reveals the characteristic lymphocytic shift, even without antibiotics.

• Textbook of Family Medicine 9e

Differential Diagnosis

• Predominant CSF neutrophils + low glucose + positive Gram stain → bacterial
• Predominantly lymphocytic + normal glucose + negative culture → aseptic
• Partially treated bacterial meningitis can mimic aseptic meningitis (lymphocytic shift, glucose normalization) — CSF bacterial antigen testing or PCR may help
• Fungi (Cryptococcus) and TB can cause lymphocytic meningitis with hypoglycorrhachia — India ink, CrAg, AFB culture/PCR are critical
• Leptospira, Lyme, syphilis — epidemiologic context + serology

Diagnosis

1. Lumbar puncture — cell count/differential, glucose, protein, Gram stain, culture
2. Viral PCR of CSF — enterovirus, HSV-1/2 (sensitivity > 95%), VZV, CMV
3. Serology — paired acute/convalescent (mumps, HSV-2, arbovirus IgM), HIV
4. Blood cultures before antibiotics if bacterial meningitis possible
5. CT before LP if focal neurologic signs or papilledema suggest mass lesion
6. Additional workup for non-infectious causes: ANA, ESR, HIV, VDRL/RPR, ACE level (sarcoid), flow cytometry (neoplastic), gadolinium MRI

Treatment

Viral (majority of cases)

• Supportive care — analgesics, antipyretics, hydration; most recover in 1–2 weeks (children) to several months (adults)
• No approved antiviral for enteroviral meningitis; pleconaril has been used in immunodeficient (agammaglobulinemic) patients
• Mumps vaccines have nearly eliminated mumps as a cause in vaccinated populations

HSV Meningitis

• IV acyclovir 5–10 mg/kg three times daily for hospitalized/symptomatic patients with HSV-2 meningitis (especially primary genital herpes association), though not proven to alter course in RCTs
• Severe HSV-2: IV acyclovir 5 mg/kg q8h × 5 days
• Recurrent (Mollaret) meningitis: oral prophylaxis with valacyclovir 500 mg/day, famciclovir 250 mg BID, or acyclovir 400 mg BID
• Goldman-Cecil Medicine; Harrison's Principles 22e

Drug-induced Aseptic Meningitis

• Identify and discontinue the offending drug (NSAIDs most common cause)
• A recent 25-year systematic review (PMID 41529234, 2026) catalogued drug-induced cases across multiple drug classes

Non-infectious / Immune-mediated

• Treat underlying disease (SLE, sarcoidosis, etc.)
• Steroids may be used for steroid-responsive causes, though withdrawal without recurrence is achieved in only ~40% of chronic cases

Prognosis

• Excellent for viral aseptic meningitis — generally self-limited
• Children recover in 1–2 weeks; adults may take several months
• Occasional recurrences (especially HSV-2 / Mollaret meningitis)
• Outcome in chronic or non-infectious aseptic meningitis depends on underlying etiology; some require indefinite treatment

• Adams and Victor's Principles of Neurology, 12e, Chapter 9
• Goldman-Cecil Medicine, International Ed., Chapter 381
• Robbins & Kumar Basic Pathology, Chapter 21
• Textbook of Family Medicine 9e, Chapter 3
• Harrison's Principles of Internal Medicine 22e, Chapter 22

Aseptic Meningitis: Vaccines & Treatment

TREATMENT

1. Supportive Care (First-line for most cases)

"Treatment of almost all cases of viral meningitis is primarily symptomatic and includes use of analgesics, antipyretics, and antiemetics." — Harrison's Principles of Internal Medicine 22e

2. Hospitalization Criteria

• Immunocompromise
• Significant alteration in consciousness
• Seizures or focal neurologic signs (raises concern for encephalitis)
• Atypical CSF profile
• Suspected bacterial meningitis pending cultures

3. Antiviral Therapy (Cause-Specific)

HSV Meningitis (HSV-1 and HSV-2)

Clinical trials have not proven that acyclovir alters the course of HSV meningitis, but it is widely used given the theoretical benefit and low toxicity. — Goldman-Cecil Medicine; Harrison's 22e

VZV Meningitis

• Oral or IV acyclovir; no specific dose proven by trials
• Shingrix (recombinant zoster vaccine) is now first-line prevention (see vaccines below)

EBV Meningitis

• Acyclovir may be used in severe cases; no proven efficacy established

HIV Meningitis (acute seroconversion)

• Antiretroviral therapy (ART) — specialist consultation recommended
• Many ART combinations considered; factors include CNS penetration, drug interactions, resistance

Arboviral Meningitis (West Nile, St. Louis, etc.)

• No specific therapy of proven benefit — supportive care only

4. Immunodeficient Patients (Enteroviral / Chronic Meningitis)

• Patients with humoral immune deficiency (e.g., X-linked agammaglobulinemia) not on IVIG should receive intramuscular γ-globulin or IV immunoglobulin (IVIg)
• Intraventricular immunoglobulin (via Ommaya reservoir) has been tried in chronic enteroviral meningitis unresponsive to systemic IgG
• Pleconaril (blocks viral attachment to host cells) has shown benefit in agammaglobulinemic patients with chronic enteroviral meningoencephalitis — not approved for routine use

Recent systematic review (PMID 38739354, 2024): IVIg therapy itself can paradoxically cause aseptic meningitis as an adverse drug reaction (drug-induced aseptic meningitis).

5. Drug-Induced Aseptic Meningitis

• Discontinue the causative drug (NSAIDs most common; also TMP-SMX, IVIg, antibiotics)
• Resolution typically follows drug withdrawal
• 25-year systematic review (PMID 41529234, 2026) documents the breadth of drug culprits

6. Non-Infectious / Immune-Mediated Causes

• SLE / vasculitis: treat the underlying autoimmune disease; corticosteroids
• Sarcoidosis: corticosteroids; chronic cases may require indefinite therapy
• Neoplastic meningitis: intrathecal or systemic chemotherapy per tumor type
• Chemical meningitis: remove causative agent; steroids may be used

VACCINES (Prevention)

Vaccines That Prevent Aseptic Meningitis

"Vaccination is an effective method of preventing the development of meningitis and other neurologic complications associated with poliovirus, mumps, measles, rubella, and varicella infection." — Harrison's Principles of Internal Medicine 22e

Vaccine-Associated Notes

• Older mumps vaccine strains (Urabe, Leningrad-Zagreb) used in some countries carried a small risk of vaccine-associated aseptic meningitis (10–100 per 100,000 vaccinees, onset 2–4 weeks post-vaccination)
• The Jeryl-Lynn strain (used in US MMR) does not carry this risk
• No vaccine currently available for the most common cause — enteroviruses (echovirus, Coxsackievirus) — making supportive care the mainstay

Summary Table