Meningitis, Viral

para>Cases of VM in the elderly are rare; consider alternative diagnoses (e.g., carcinomatous meningitis, NSAID- or medication-induced meningitis).

GENERAL PREVENTION

Limit exposure to known hosts. Observe hand washing and general hygiene procedures.

COMMONLY ASSOCIATED CONDITIONS

Encephalitis; neurologic deficits; myopericarditis; neonatal enteroviral sepsis

DIAGNOSIS

HISTORY

Predominant symptoms include acute onset (hours to days) of:

Fever (in 76 " 100% of patients)
Headache (prominent early symptom)
Photophobia
Myalgias
Nausea, vomiting
Malaise
Nuchal rigidity (>50%)
Mental status changes
- Encephalitis is associated with other neurologic dysfunction, such as behavioral change, focal neurologic deficits, seizure. There is a continuum between meningitis and encephalitis that can be labeled as one or the other according to predominant symptom type, or jointly labeled "meningoencephalitis. "

Also document the following:

Travel and exposure history
Sexual activity (e.g., HSV, HIV)
Outdoor activities (Lyme disease)
Exposure to rodent feces and/or urine (LCMV)
Solid-organ transplant (LCMV, CMV)
Immunocompromised host (CMV, HSV, adenovirus)
History of varicella-zoster infection (VZV)
Immunization status (mumps virus)

PHYSICAL EXAM

Altered mental status (AMS)
- AMS is more common in encephalitis than meningitis.
Fever (>100.4 °F/38 °C)
Meningeal signs (should not be used exclusively to diagnose or rule out meningitis):
- Nuchal rigidity
- Brudzinski sign: Neck flexion elicits involuntary hip and knee flexion in supine patient.
- Kernig sign: resistance to knee extension following flexion of hips to 90 degrees by physician
- Jolt accentuation test: Rapid horizontal rotation of the head accentuates the headache
Genital lesions (HSV2: can precede meningeal symptoms by up to a week)
Parotitis (mumps)
Asymmetric flaccid paralysis (West Nile virus)
Mucocutaneous findings
- Vesicular rash in hand, foot, and mouth disease (coxsackie)
- Herpangina (coxsackie A)
- Herpes zoster rash (VZV)
- Erythema chronicum migrans or cranial neuropathy (Lyme disease [Borrelia burgdorferi])
- Generalized maculopapular rash (Echovirus 9)
- Oropharyngeal thrush (HIV)
- Petechial rash (Neisseria meningitidis)

DIFFERENTIAL DIAGNOSIS

Bacterial meningitis (BM)
Encephalitis
Other infectious agents:
- Tuberculosis; syphilis; leptospirosis; Lyme disease; Rocky Mountain spotted fever; ehrlichiosis; Coccidioides; Cryptococcus neoformans; amebiasis; Rickettsial infection
Parameningeal infections (e.g., subdural empyema)
Postinfectious encephalomyelitis
Viral syndrome (e.g., influenza)
Leukemia or carcinomatous meningitis
Migraine/tension headache
Acute metabolic encephalopathy
Chemical meningitis
Drug-induced meningitis (NSAIDs, IVIG, Bactrim)
Brain/epidural abscess

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Rule out BM:
- There is debate over whether patients with low suspicion of BM need a lumbar puncture (LP). Some authors contend that if meningeal symptoms have been present >48 hours with a normal neurologic exam in an immunocompetent patient with confirmed normal level of alertness, BM is extremely unlikely and LP is not warranted. Others contend that BM cannot be excluded clinically and to exercise caution discharging meningitic patients without LP.
- Bacterial Meningitis Score (BMS): The BMS is a validated clinical decision rule to identify at very low risk of BM. Low-risk features include negative CSF Gram stain, CSF absolute neutrophil count (ANC) <1,000 cells/ ΌL, CSF protein <80 mg/dL, peripheral blood ANC <10,000 cells/ ΌL, and no seizure around the time of initial presentation.
- CSF bacterial culture is positive in 80 " 90% of BM patients who haven 't received antibiotics for 2 to 4 hours prior to LP.
LP is the standard of care for suspected BM:
- If BM is suspected, start antibiotics immediately.
- Contraindications for LP: signs of increased intracranial pressure (e.g., focal neurologic findings, papilledema, altered mental status, vomiting), known ventricular obstruction, new onset seizure, immunocompromised state, local infection over potential LP site or suspected epidural abscess, use of anticoagulation or coagulopathy, and possibility of cardiorespiratory compromise due to patient positioning during procedure
- Post-LP headache: occurs in 37% of patients within 48 hours
- CSF analysis: glucose, protein, WBC count with differential, RBC count, Gram stain, culture; consider CSF lactate:
  - CSF lactate elevation can differentiate BM from VM (decreased sensitivity if pretreated with antibiotics) (1,2)[A].
Typical CSF findings in VM
- Elevated WBC count: 10 to 1,000/mm3, classically lymphocyte predominance (less consistent in younger patients); May show neutrophil predominance in first 48 hours
- Decreased or normal glucose (relative to concurrent serum glucose)
- Protein normal to slightly elevated (<150 mg/dL)
- Negative Gram stain and bacterial culture
- Elevated opening pressure
- RBCs in CSF (Consider HSV meningitis/encephalitis.)
- Pathogen identification
  - Gold standard: CSF viral culture for enteroviruses, HSV, and mumps has low sensitivity (<6%); viral culture may yield no additional information over nucleic acid amplification alone.
  - Polymerase chain reaction (PCR): has a sensitivity of 95 " 100% for HSV-1 and -2, EBV, and enterovirus
  - RT PCR test is approved by the FDA for enteroviral meningitis. Results in 2 to 3 hours
  - Serology can be performed for many arthropod-borne viruses.
Other labs: CBC, blood culture, blood glucose; consider serum CRP and procalcitonin (PCT).
- CBC: normal or mildly elevated WBCs
- Multiple studies show PCT correlation with BM. PCT levels of >0.25 to 2.13 are 90% sensitive and 98% specific for BM. Elevated serum CRP was 82% sensitive and 81% specific (1,3)[B].
Consider EEG if concern for encephalitis.
Indication for imaging depends on clinical scenario. Perform CT prior to LP if papilledema, spinal cord trauma, altered mental status, or focal neurologic findings. CT scan not typically clinically necessary in the absence of risk factors.

Follow-Up Tests & Special Considerations
Disorders that may alter lab results:

Diabetes: Consider current blood sugar level to correlate with CSF glucose level.
Preexisting neurologic diseases (e.g., intracranial neoplasm, demyelinating disease)

TREATMENT

GENERAL MEASURES

Management is largely supportive care (e.g., pain control, IV fluids).

MEDICATION

First Line

Analgesics (adult doses; titrate doses to pain relief)
- Morphine 2.5 to 5 mg IV
- Hydromorphone (Dilaudid) 1 to 2 mg IV
- Hydrocodone (Norco) 5/325 mg 1 to 2 tablets PO q6h OR oxycodone (Percocet) 5/325 mg 1 to 2 tablets PO q4 " 6h
Antiemetics
- Ondansetron (Zofran) 4 to 8 mg IV q8h
- Metoclopramide (Reglan) 10 to 20 mg IV/IM q4 " 6h
Antipyretics: acetaminophen (Tylenol) 650 mg PO or rectal suppository q4h
Antiviral agents: Initiate empiric acyclovir at 10 mg/kg IV q8h for patients with CSF pleocytosis, negative Gram stain, and suspicion for HSV while awaiting results of definitive (e.g., HSV PCR) testing.
Antibiotics
- Not indicated for treatment of VM
- If unclear etiology, treat symptomatically and follow the patient closely in the hospital setting while awaiting laboratory results.
- If in doubt, initiate an IV broad-spectrum antibiotic with good CSF penetration. Consider especially in elderly, <3 month old, or immunocompromised patient. Empiric treatment for BM in otherwise healthy patient
  - If <1 month, consider ampicillin PLUS gentamicin OR cefotaxime. All dosing dependent on age and size.
  - If 1 month to 17 years old, consider vancomycin PLUS ceftriaxone OR cefotaxime. Dosing dependent on age and size.
  - If 18 years to 49 years old, consider vancomycin (15 to 20 mg/kg/dose q8 " 12h; also consider loading dose of 25 to 30 mg/kg) PLUS ceftriaxone (2g q12h) OR cefotaxime (2g q4 " 6h).
  - In >50 years old, consider vancomycin (15 to 20 mg/kg/dose q8 " 12h; also consider loading dose of 25 to 30 mg/kg) PLUS ampicillin (150 to 250 mg/kg/day divided q3 " 4h) PLUS ceftriaxone (2g q12h) OR cefotaxime (2g q4 " 6h).
If concern for BM, consider corticosteroids along with antibiotic therapy.

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization
Generally, VM is treated as outpatient. Patients with VM and complications (encephalitis) may be hospitalized. Hospitalize for empiric antibiotic therapy, pain/fluid control, immunocompromised patient, or <1 year old.

Study of ED visits found that most children diagnosed with VM were hospitalized (91%).

IV Fluids
Crystalloid bolus or continuous infusion, based on hydration status and clinical presentation
Nursing

Neurologic monitoring for changes in mental status, fever, and other clinical indicators to assess disease progression
Contact precautions until BM is ruled out
Private room indicated with sterile precautions
Encourage hand washing.

Discharge Criteria
Discharge depends on likelihood of BM, CSF, WBC count, and clinical parameters such as dehydration, functional level, social circumstances, and ability to follow up.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Primary care follow up to ensure resolution.
Patient Monitoring

Monitor for relapse or exacerbation of symptoms.
Monitor for neurologic/neuroendocrine complications:
- Seizures, cerebral edema, syndrome of inappropriate antidiuretic hormone (SIADH)
- Assess ability to have companion monitor change in mental/neurologic status if patient discharged.

DIET

Consider NPO if nausea or vomiting. Advance to clear fluids/regular diet as tolerated.

PATIENT EDUCATION

Discuss low probability of transmission to contacts.
Expected duration of illness is 5 to 10 days.
Recurrence of headache, myalgia, weakness is possible over 2 to 3 weeks

PROGNOSIS

Complete recovery generally within 7 to 10 days
Headaches and other neurologic symptoms may persist intermittently for weeks to months.
Only 0.6% of hospitalizations for VM result in death.
European studies suggest potential residual postmeningeal cognitive impairment.

COMPLICATIONS

Fatigue, irritability, muscle weakness, seizures/abscess/mastoiditis (rare)

REFERENCES

11 Viallon A, Desseigne N, Marjollet O, et al. Meningitis in adult patients with a negative direct cerebrospinal fluid examination: value of cytochemical markers for differential diagnosis. Crit Care. 2011;15(3):R136.22 Sakushima K, Hayashino Y, Kawaguchi T, et al. Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: a meta-analysis. J Infect. 2011;62(4):255 " 262.33 Vikse J, Henry BM, Roy J, et al. The role of serum procalcitonin in the diagnosis of bacterial meningitis in adults: a systematic review and meta-analysis. Int J Infect Dis. 2015;38:68 " 76.

ADDITIONAL READING

Ciovacco WA, Baraff LJ. Lumbar puncture is not needed for all patients suspected to have viral meningitis. Ann Emerg Med. 2012;59(3):228 " 229.
Mohseni MM, Wilde JA. Viral meningitis: which patients can be discharged from the emergency department? J Emerg Med. 2012;43(6):1181 " 1187.
Nigrovic LE, Fine AM, Monuteaux MC, et al. Trends in the viral management of viral meningitis at United States children 's hospitals. Pediatrics. 2013;131(4):670 " 676.
Polage CR, Petti CA. Assessment of the utility of viral culture of cerebrospinal fluid. Clin Infect Dis. 2006;43(12):1578 " 1579.
Studahl M, Lindquist L, Eriksson BM, et al. Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management. Drugs. 2013;73(2):131 " 158.
Swadron SP. Pitfalls in the management of headache in the emergency department. Emerg Med Clin North Am. 2010;28(1):127 " 147.
Talan DA. Bacterial cause of suspected meningitis cannot be safely excluded without cerebrospinal fluid analysis. Ann Emerg Med. 2012;59(3):227 " 228.
Thomas KE, Hasbun R, Jekel J, et al. The diagnostic accuracy of Kernig 's sign, Brudzinski 's sign, and nuchal rigidity in adults with suspected meningitis. Clin Infect Dis. 2002;35(1):46 " 52.

CODES

ICD10

A87.9 Viral meningitis, unspecified
A87.1 Adenoviral meningitis
A87.0 Enteroviral meningitis
B00.3 Herpesviral meningitis
A87.2 Lymphocytic choriomeningitis
A87.8 Other viral meningitis
B02.1 Zoster meningitis

ICD9

047.9 Unspecified viral meningitis
049.1 Meningitis due to adenovirus
047.1 Meningitis due to echo virus
047.0 Meningitis due to coxsackie virus
054.72 Herpes simplex meningitis
053.0 Herpes zoster with meningitis
047.8 Other specified viral meningitis

SNOMED

58170007 Viral meningitis (disorder)
111850006 Adenoviral meningitis
192667007 Echovirus meningitis
111878007 Coxsackie meningitis
10491005 Herpes zoster with meningitis (disorder)
23291008 Herpes simplex meningitis (disorder)

CLINICAL PEARLS

Viral meningitis cannot always be reliably distinguished from BM based on clinical findings. Potential cases of BM should be hospitalized for evaluation and treatment pending laboratory results.
VM is more common than BM in children.
Antibiotic administration >2 to 4 hours prior to CSF analysis may result in "partially treated " BM that mimics VM.
IV acyclovir should be administered if there is high clinical suspicion for HSV.
If BM is suspected, broad-spectrum antibiotics should be administered until BM has been ruled out.
Morbidity with VM is low but increases if there is associated encephalitis.

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