Viral Meningitis

Viral meningitis is the most common form of meningitis, with an annual incidence of approximately 2.7–7.6 per 100,000 adults.[1-2] It is an inflammation of the meninges characterized by acute onset of meningeal symptoms, fever, CSF pleocytosis, and no growth on routine bacterial culture.[3] While generally self-limiting, it is not always benign — up to 20% of patients have unfavorable outcomes at 30 days, and long-term neuropsychiatric sequelae are increasingly recognized.[1][4]

1. History

• Headache is nearly universal (99–100%), typically severe, diffuse, and worsened by movement[5-6]
• Fever present in 65–81%; may be absent at time of presentation (only 48% febrile ≥38°C on arrival)[5-6]
• Photophobia/phonophobia in 63–77%[5-6]
• Nausea/vomiting in ~76%[5]
• Neck stiffness reported by only 37–50% of patients[5-6]
• The classic triad of headache + neck stiffness + photophobia is present in only 28%[1]
• Onset typically acute over 1–3 days; median 2 days from symptom onset to presentation[5]
• Ask about prodromal illness: upper respiratory symptoms (~14%) or gastroenteritis (~16%) suggest enteroviral etiology[5]
• Ask about sick contacts — concurrent illness in family/relatives in 53% of enterovirus cases[5]
• Ask about genital herpes history (HSV-2), shingles/varicella (VZV), recent travel, tick exposure, HIV risk factors[1][7]
• Seasonality: enterovirus peaks summer–autumn; HSV-2 and VZV are year-round[5][8]

2. Alarm Features

• Altered mental status/decreased consciousness — suggests encephalitis or bacterial meningitis; the triad of fever + neck stiffness + decreased consciousness essentially never occurs in isolated viral meningitis[2]
• Seizures — rare in viral meningitis (0% in one cohort); consider HSV encephalitis, bacterial meningitis[6]
• Focal neurologic deficits — suggest encephalitis or space-occupying lesion[9]
• Petechial/purpuric rash — meningococcemia until proven otherwise[9]
• Rapidly progressive symptoms or hemodynamic instability
• Immunocompromised state — higher risk of atypical pathogens and severe disease[8-9]
• Neonates and infants — nonspecific presentations; higher morbidity[9]
• Papilledema — suggests raised intracranial pressure; obtain imaging before LP

3. Medications

• Empiric antibiotics (ceftriaxone + vancomycin ± ampicillin) should be started immediately when bacterial meningitis cannot be excluded, and discontinued once aseptic meningitis is confirmed[9-10]
• Acyclovir should be started empirically if HSV encephalitis is suspected; however, for isolated HSV-2 or VZV meningitis (without encephalitis), early antiviral treatment was not associated with improved outcomes in a large prospective cohort[1]
• Approximately 21% of patients with undiagnosed lymphocytic meningitis receive unnecessary acyclovir courses[4]
• Drug-induced aseptic meningitis is an important consideration — common culprits include NSAIDs (especially ibuprofen), trimethoprim-sulfamethoxazole, IVIG, intrathecal agents, and monoclonal antibodies[6]
• Supportive medications: analgesics (acetaminophen, NSAIDs), antiemetics, IV fluids
• Dexamethasone is recommended for suspected bacterial meningitis (10 mg IV q6h × 4 days) but has no established role in viral meningitis[9-10]

4. Diet

• No specific dietary triggers or restrictions
• Adequate hydration is essential, particularly with fever, nausea, and poor oral intake
• Patients with significant nausea/vomiting may require IV fluid resuscitation
• No long-term dietary modifications needed

5. Review of Systems

• Neurologic: headache character/severity, photophobia, phonophobia, confusion, vision changes, weakness, numbness, seizures
• Constitutional: fever, chills, malaise, fatigue, myalgias
• GI: nausea, vomiting, diarrhea (enteroviral prodrome)
• Respiratory: cough, rhinorrhea, sore throat (enteroviral prodrome)
• Dermatologic: vesicular rash (HSV genital lesions, zoster dermatome), petechiae/purpura (meningococcal)
• Genitourinary: genital lesions, urinary retention (sacral radiculitis with HSV-2)
• Musculoskeletal: myalgias, arthralgias

6. Collateral History and Family History

• Sick contacts — concurrent febrile or GI illness in household members strongly suggests enterovirus (present in 53% of enterovirus meningitis cases)[5]
• Daycare/school exposure in pediatric contacts
• Sexual history — HSV-2 serostatus, new partners (HSV-2 is the second most common cause at ~16%)[1]
• Travel history — arboviruses (West Nile, Japanese encephalitis, Toscana, Dengue, Zika)[7]
• Tick exposure — tick-borne encephalitis[7]
• Immunosuppression — HIV status, transplant, chemotherapy; VZV meningitis associated with immunosuppression in 20% of cases[1]
• Previous episodes of meningitis — recurrent episodes suggest Mollaret meningitis (HSV-2), seen in ~22% of HSV-2 meningitis patients[11]
• Family history of immunodeficiency or recurrent infections may suggest genetic susceptibility[12]

7. Risk Factors

• Age: young adults most commonly affected (median age 31–33 years)[1][5]
• Female sex: 54% of cases; 77% of HSV-2 meningitis cases are female; females have higher risk of unfavorable outcomes (aRR 1.34)[1]
• Summer–autumn season for enterovirus[5]
• Immunosuppression: particularly for VZV meningitis (20% immunosuppressed)[1]
• HSV-2 seropositivity: risk factor for both primary and recurrent (Mollaret) meningitis[11-12]
• HIV infection: associated with aseptic meningitis at seroconversion and increased susceptibility[6]
• Close-contact settings: dormitories, military barracks, daycare (enterovirus transmission)
• Lack of vaccination: measles, mumps, varicella, Japanese encephalitis in endemic areas[7]

8. Differential Diagnosis

• The critical task in the ED is distinguishing viral meningitis from bacterial meningitis, which is a medical emergency.[6]
• Bacterial meningitis — more toxic appearance, altered mental status (60–69%), higher CSF WBC (usually >1000/μL), neutrophilic predominance, elevated protein (>100 mg/dL), low glucose (<30 mg/dL), positive Gram stain (50–90% sensitivity)[9][13]
• HSV encephalitis — altered mental status, seizures, temporal lobe findings on MRI; requires urgent IV acyclovir[7]
• Tuberculous meningitis — subacute onset, cranial nerve palsies, basilar enhancement, CSF lymphocytic with very low glucose[8]
• Fungal meningitis (Cryptococcus) — immunocompromised patients, subacute/chronic course, elevated opening pressure[14]
• Subarachnoid hemorrhage — thunderclap headache, xanthochromia; 8% of enterovirus meningitis initially misdiagnosed as SAH[5]
• Drug-induced aseptic meningitis — temporal relationship with offending medication[15]
• Autoimmune/inflammatory meningitis — SLE, neurosarcoidosis, Behçet disease, anti-NMDAR encephalitis[15]
• Meningeal carcinomatosis — subacute, cranial neuropathies, known malignancy[13]
• Neurosyphilis — should be considered in undiagnosed aseptic meningitis, especially with HIV risk factors[6]

9. Past Medical History

• Previous episodes of meningitis — recurrence in 2% of viral meningitis; Mollaret meningitis defined as ≥3 self-resolving episodes[5][15]
• HSV-2 infection — genital herpes history; 22% progression risk from single-episode to recurrent meningitis[11]
• Immunocompromising conditions — HIV/AIDS, transplant, chemotherapy, biologics
• Varicella/zoster history — VZV meningitis associated with concurrent shingles in 60%[1]
• Vaccination history — MMR, varicella, meningococcal
• Neurosurgical history — VP shunt raises concern for bacterial etiology
• Autoimmune conditions — may cause aseptic meningitis or predispose to infections

10. Physical Exam

• Vital signs: temperature ≥38°C in ~48% at presentation; tachycardia common; hypotension suggests sepsis/bacterial etiology[5]
• Mental status: should be normal or near-normal in viral meningitis; altered mentation (present in 60–69% of bacterial meningitis) is a red flag[9]
• Nuchal rigidity: present in 37–50% of viral meningitis[5-6]
• Kernig sign: low sensitivity (2–23%)[9]
• Brudzinski sign: low sensitivity (2–28%)[9]
• Jolt accentuation test: sensitivity 52–65% for meningitis[9]
• Skin exam: vesicular lesions (HSV, VZV dermatomal rash); petechiae/purpura (meningococcal — urgent escalation)
• Cranial nerves: deficits suggest encephalitis or raised ICP
• Fundoscopy: papilledema warrants imaging before LP
• Genital exam: if HSV-2 suspected, look for active herpetic lesions

11. Lab Studies

CSF analysis is the cornerstone of diagnosis

• The following table summarizes typical CSF findings by infection type:
• Table 2. CSF Characteristics by Infection Type Cerebrospinal Fluid Analysis. Am Fam Physician. March 31, 2021.

Key CSF findings in viral meningitis

• WBC: typically 100–1,000/μL (median 160, IQR 60–358); lymphocyte predominance (though early PMN predominance can occur, especially with enterovirus)[1][8]
• Protein: normal or mildly elevated
• Glucose: usually normal (decreased in only ~25% of mumps cases)[14]
• CSF lactate: low (helps distinguish from bacterial; AUC 0.98)[13]

Serum studies

• CBC, CRP (median CRP 8 mg/L in enterovirus — much lower than bacterial)[5]
• Procalcitonin: excellent discriminator for bacterial vs. viral (sensitivity 95%, specificity 97%, AUC 0.98); combined PCT + CSF protein yields AUC 0.998[13][16]
• Blood cultures (×2) — to rule out bacteremia
• HIV testing — should be considered in all undiagnosed aseptic meningitis[6]
• RPR/VDRL if neurosyphilis is a concern[6]

12. Imaging

• CT head before LP is indicated only if: focal neurologic deficits, papilledema, altered mental status, new-onset seizures, or immunocompromised state[9]
• Unnecessary neuroimaging delays LP and decreases pathogen yield[4]
• MRI brain with contrast if encephalitis is suspected (temporal lobe signal changes in HSV encephalitis)
• Routine imaging is not necessary in an immunocompetent patient with classic meningitis presentation and no red flags

13. Special Tests

• CSF multiplex PCR (e.g., BioFire FilmArray Meningitis/Encephalitis Panel): rapid identification of viral pathogens; 24/7 availability significantly reduces hospitalization rate (73.9% → 42.0%), antibiotic use, and length of stay[17]
• CSF enterovirus PCR: most important single test; rapid turnaround enables early antibiotic discontinuation[6][17]
• CSF HSV-1/2 PCR: essential to distinguish meningitis from encephalitis
• CSF VZV PCR: particularly in immunocompromised or patients with concurrent shingles
• Bacterial Meningitis Score and validated risk scores can help stratify low-risk patients (99.5–100% sensitivity for ruling out bacterial meningitis)[13]
• Opening pressure: typically normal in viral meningitis; elevated in bacterial or cryptococcal

14. ECG

• Not routinely indicated for viral meningitis
• Consider ECG if enteroviral myocarditis is suspected (chest pain, dyspnea, tachycardia out of proportion)
• ECG monitoring if hemodynamically unstable or sepsis is a concern
• Enterovirus D68 and Coxsackievirus B are associated with myocarditis/pericarditis

15. Assessment

• Viral meningitis is the most common cause of meningitis overall (~72% of all meningitis cases)[13]
• Most common pathogens: enteroviruses (39%), HSV-2 (16%), VZV (15%); pathogen unidentified in 27%[1]
• The classic triad is present in only 28% — absence does not rule out meningitis[1]
• Despite being labeled "benign," 20% have unfavorable outcomes at 30 days (GOS 1–4)[1]
• Long-term sequelae include headache (28% at 6 months), fatigue (31%), cognitive impairment (36%), and sleep disturbance (31%)[18-19]
• At 6 months post-infection, approximately 25% of patients have reduced or no work ability[19]
• Outcomes are similar across viral etiologies; female sex is an independent risk factor for unfavorable outcome[1]

16. Treatment Plan

Initial stabilization

• IV access, fluid resuscitation if dehydrated, antipyretics, analgesics, antiemetics

Empiric therapy (until bacterial meningitis excluded)

• Ceftriaxone 2g IV q12h + vancomycin 15–20 mg/kg IV q8–12h[9]
• Add ampicillin 2g IV q4h if Listeria risk (age >50, pregnancy, immunocompromised)[9]
• Dexamethasone 0.15 mg/kg IV q6h × 4 days — give with or before first antibiotic dose if bacterial meningitis suspected[9-10]
• Acyclovir 10 mg/kg IV q8h if HSV encephalitis is a concern[10]

Once viral meningitis confirmed

• Discontinue antibiotics[9]
• Supportive care: analgesics, hydration, rest in a dark/quiet room
• Antivirals are not routinely recommended for HSV-2 or VZV meningitis (without encephalitis) — early antiviral treatment was not associated with improved outcomes[1][4]
• For Mollaret meningitis: IV acyclovir during acute episodes is standard practice, though evidence for prevention of recurrence is limited; some patients use patient-initiated episodic valacyclovir at symptom onset[20-21]

17. Disposition

Admission criteria

• Diagnostic uncertainty (cannot exclude bacterial meningitis pending cultures/PCR)
• Altered mental status or focal neurologic deficits
• Immunocompromised patients
• Inability to tolerate oral intake
• Significant comorbidities or extremes of age
• Suspected encephalitis

Discharge from ED may be appropriate if

• Rapid CSF viral PCR confirms enteroviral etiology[17]
• Patient is well-appearing, tolerating PO, normal mental status
• Reliable follow-up available
• 24/7 multiplex PCR availability reduced hospitalization from 74% to 42%[17]
• Median length of stay: 4 days (can be reduced to <1 day with rapid on-site PCR)[4][17]

Specialist consultation triggers

• Infectious diseases: atypical CSF profile, immunocompromised, HIV-associated
• Neurology: seizures, focal deficits, suspected encephalitis, recurrent meningitis
• ICU: hemodynamic instability, respiratory compromise, severely altered mental status

18. Follow Up / Return Precautions

Follow-up timing

• Outpatient follow-up at 1 month — assess for persistent symptoms[19]
• Consider repeat assessment at 3 and 6 months given high rates of persistent sequelae[19]
• Neuropsychological testing should be considered if cognitive complaints persist (utilized in only 26% of patients in one cohort)[19]
• Return precautions — instruct patients to return immediately for:
• Worsening or new-onset confusion/altered behavior
• New seizures
• Worsening headache unresponsive to analgesics
• High fever (>39°C) or inability to keep fluids down
• New rash (especially petechial/purpuric)
• Neck stiffness worsening
• Vision changes or new weakness

Patient counseling

• Most patients recover fully within 7–18 days of acute symptoms[9]
• However, persistent symptoms are common: headache (56% at 1 month, 28% at 6 months), concentration difficulty, fatigue, sound sensitivity[19]
• At 6 months, ~25% still have reduced work capacity; female sex and lower GOS at discharge predict slower return to work[19]
• Reassure that viral meningitis is not typically contagious person-to-person (though enteroviruses spread via fecal-oral/respiratory routes — hand hygiene is important)
• For HSV-2 meningitis: counsel about 22% risk of recurrence (Mollaret meningitis) and to seek care promptly with recurrent symptoms[11]

References

1. Clinical Features and Prognostic Factors in Adults With Viral Meningitis. — Petersen PT, Bodilsen J, Jepsen MPG, et al. Brain : A Journal of Neurology. 2023.

2. Red and Orange Flags for Secondary Headaches in Clinical Practice: SNNOOP10 List. — Do TP, Remmers A, Schytz HW, et al. Neurology. 2019.

3. Viral (Aseptic) Meningitis: A Review. — Wright WF, Pinto CN, Palisoc K, Baghli S. Journal of the Neurological Sciences. 2019.

4. Incidence, Aetiology, and Sequelae of Viral Meningitis in UK Adults: A Multicentre Prospective Observational Cohort Study. — McGill F, Griffiths MJ, Bonnett LJ, et al. The Lancet. Infectious Diseases. 2018.

5. Enterovirus Meningitis in Adults: A Prospective Nationwide Population-Based Cohort Study. — Bodilsen J, Mens H, Midgley S, et al. Neurology. 2021.

6. The impact of cerebrospinal fluid viral polymerase chain reaction testing on the management of adults with viral meningitis: A multi‐center retrospective study. — Kim MG, Gulholm T, Lennard K, et al. Journal of Medical Virology. 2023.

7. Viral Meningitis and Encephalitis: An Update. — Gundamraj V, Hasbun R. Current Opinion in Infectious Diseases. 2023.

8. Diagnostic Test Accuracy of Jolt Accentuation for Headache in Acute Meningitis in the Emergency Setting. — Iguchi M, Noguchi Y, Yamamoto S, Tanaka Y, Tsujimoto H. The Cochrane Database of Systematic Reviews. 2020.

9. Aseptic and Bacterial Meningitis: Diagnosis, Treatment, and Prevention. — Krebs L, Durden B, Saguil A. American Family Physician. 2026.

10. Clinical Reasoning: A 44-Year-Old Woman With Headache Followed by Sudden Neurologic Decline. — Berkowitz AL, Kimchi EY, Hwang DY, et al. Neurology. 2013.

11. Benign Recurrent Lymphocytic Meningitis (Mollaret's Meningitis) in Denmark: A Nationwide Cohort Study. — Petersen PT, Bodilsen J, Jepsen MPG, et al. European Journal of Neurology. 2024.

12. Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis. — Hait AS, Thomsen MM, Larsen SM, et al. The Journal of Infectious Diseases. 2021.

13. Progress and Challenges in Bacterial Meningitis: A Review. — Hasbun R. The Journal of the American Medical Association. 2022.

14. Cerebrospinal Fluid Analysis. — Shahan B, Choi EY, Nieves G. American Family Physician. 2021.

15. Clinical Reasoning: A 35-Year-Old Man With 2 Episodes of Meningoencephalitis Associated With Flu-Like Illnesses. — Amin AJ, Lewis SL. Neurology. 2015.

16. Microbial Aspects and Potential Markers for Differentiation Between Bacterial and Viral Meningitis Among Adult Patients. — Alnomasy SF, Alotaibi BS, Mujamammi AH, Hassan EA, Ali ME. PloS One. 2020.

17. Impact of a 24/­7 Multiplex-PCR on the Management of Patients With Confirmed Viral Meningitis. — Péan de Ponfilly G, Chauvin A, Salmona M, et al. The Journal of Infection. 2021.

18. Long-Term Sequelae After Viral Meningitis and Meningoencephalitis Are Frequent, Even in Mildly Affected Patients, a Prospective Observational Study. — Schwitter J, Branca M, Bicvic A, et al. Frontiers in Neurology. 2024.

19. Ability to Return to Work and Persistent Symptoms Six Months After Viral Meningitis - A Retrospective Single-Centre Cohort Study. — Imishti A, Nissen MJ, Øvrehus A, Larsen L. Infectious Diseases. 2025.

20. Recurrent Herpes Simplex Virus Type 2 Mollaret Meningitis in a Man Living With HIV: A Case Report and Patient-Initiated Episodic Valacyclovir Strategy. — Wakutsu T, Inoue E, Nakamoto T, et al. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. 2026.

21. The Neurotropic Herpes Viruses: Herpes Simplex and Varicella-Zoster. — Steiner I, Kennedy PG, Pachner AR. The Lancet. Neurology. 2007.