Residency · Residency · Emergency Medicine
Meningitis and Encephalitis in the ED
Introduction
Meningitis and encephalitis represent infections of the central nervous system that carry significant morbidity and mortality if not recognized and treated promptly. Bacterial meningitis has a mortality rate of 15 to 25 percent even with appropriate therapy, and delays in antibiotic administration are directly associated with worse outcomes. The emergency physician must maintain a high index of suspicion, initiate empiric treatment rapidly, and understand the diagnostic nuances of CSF analysis.
Definitions
Meningitis is inflammation of the meninges (the pia and arachnoid mater) surrounding the brain and spinal cord, presenting primarily with headache, neck stiffness, and fever. Encephalitis is inflammation of the brain parenchyma itself, presenting with altered mental status, behavioral changes, seizures, and focal neurological deficits. Meningoencephalitis is the overlap syndrome featuring elements of both and is common in viral etiologies such as HSV.
Etiology by Age and Risk Factors
Bacterial Meningitis
In neonates under 1 month, the common organisms are Group B Streptococcus, Escherichia coli, and Listeria monocytogenes. In infants and children aged 1 month to 18 years, Neisseria meningitidis and Streptococcus pneumoniae predominate. In adults aged 18 to 50, S. pneumoniae is the most common organism, followed by N. meningitidis. In adults over 50 years and immunocompromised patients, S. pneumoniae, L. monocytogenes, and gram-negative bacilli are the major concerns. In post-neurosurgical or VP shunt patients, Staphylococcus aureus, coagulase-negative staphylococci, and gram-negative bacilli are the primary pathogens.
Viral Meningitis
Enteroviruses are the most common cause of aseptic meningitis. Other viral causes include HSV-2 (which can cause recurrent lymphocytic meningitis), HIV, mumps, and arboviruses.
Encephalitis
HSV-1 is the most common cause of sporadic fatal encephalitis and characteristically affects the temporal lobes. Arboviruses, including West Nile, Eastern equine encephalitis, and St. Louis encephalitis, carry seasonal and geographic risk patterns. Autoimmune encephalitis, particularly anti-NMDA receptor encephalitis, is increasingly recognized, especially in young women.
Clinical Presentation
The classic triad of bacterial meningitis consists of fever, nuchal rigidity, and altered mental status, but this triad is present in only 44 percent of patients. At least two of the four cardinal features (fever, neck stiffness, headache, and altered mental status) are present in 95 percent of cases. The Kernig sign is positive when extending the knee with the hip flexed to 90 degrees causes pain. The Brudzinski sign is positive when passive neck flexion causes involuntary hip and knee flexion. However, the sensitivity of these meningeal signs is limited at 5 to 30 percent, meaning their absence does not exclude meningitis. A petechial or purpuric rash is highly concerning for meningococcemia and represents a medical emergency. Encephalitis is distinguished by altered mental status, personality or behavioral changes, seizures, focal neurological deficits, movement disorders, and aphasia.
<image>Clinical illustration showing two examination techniques for meningitis: Kernig sign (examiner extending the patient's knee with hip flexed at 90 degrees causing pain) and Brudzinski sign (passive neck flexion causing involuntary hip and knee flexion), with anatomical annotations</image>
Diagnostic Approach
CT Before LP
A CT scan before LP is indicated in patients with immunocompromise, a history of CNS disease, new-onset seizures, papilledema, altered mental status, or focal neurological deficits. A normal CT does not eliminate the risk of herniation but significantly reduces it. Crucially, antibiotics should not be delayed while awaiting CT or LP. If bacterial meningitis is suspected, empiric antibiotics should be administered immediately.
Lumbar Puncture and CSF Analysis
CSF findings differ by etiology. Bacterial meningitis typically produces a WBC count above 1000 with neutrophil predominance, glucose below 40 mg/dL, protein above 250 mg/dL, and elevated opening pressure. Viral meningitis shows 10 to 500 WBCs with lymphocyte predominance, normal glucose, and mildly elevated protein at 50 to 100 mg/dL. HSV encephalitis shows 10 to 500 WBCs with lymphocyte predominance, normal to low glucose, and elevated protein. Fungal and TB meningitis show 10 to 500 WBCs with lymphocyte predominance, low glucose, very elevated protein, and elevated opening pressure.
| CSF Parameter | Bacterial | Viral | HSV Encephalitis | TB/Fungal |
|---|---|---|---|---|
| WBC (cells/μL) | > 1000 | 10–500 | 10–500 | 10–500 |
| Predominant cell | Neutrophils | Lymphocytes | Lymphocytes (± RBCs) | Lymphocytes |
| Glucose | < 40 mg/dL | Normal | Normal to low | Low |
| Protein | > 250 mg/dL | 50–100 mg/dL | Elevated | Very elevated |
| Opening pressure | Elevated | Normal to mildly elevated | Normal to elevated | Elevated |
| Key test | Gram stain (60–90% sensitive) | Enterovirus PCR | HSV PCR (96% sensitive) | AFB smear/culture; India ink; CrAg |
Additional CSF Studies
The Gram stain is positive in 60 to 90 percent of untreated bacterial meningitis. CSF culture is the gold standard and remains positive for several hours after antibiotic administration. HSV PCR has a sensitivity of 96 percent and specificity of 99 percent for HSV encephalitis but may be falsely negative in the first 72 hours. Multiplex PCR panels such as the BioFire FilmArray provide rapid identification of common bacterial, viral, and fungal pathogens within 1 hour. CSF lactate above 3.5 mmol/L supports a bacterial etiology with a sensitivity of 93 percent and specificity of 96 percent.
Neuroimaging
CT of the head is primarily used to rule out contraindications to LP and may show cerebral edema, hydrocephalus, or abscess. MRI with contrast is the study of choice for encephalitis. HSV encephalitis classically shows bilateral asymmetric temporal lobe hyperintensity on T2 and FLAIR sequences.
<image>MRI brain FLAIR sequence showing bilateral asymmetric temporal lobe hyperintensity characteristic of HSV encephalitis, with annotations pointing to the medial temporal lobes and insular cortex involvement</image>
Empiric Treatment
Antibiotics -- Do Not Delay
| Age/Risk Group | Empiric Regimen | Key Organisms Covered |
|---|---|---|
| Neonates (< 1 month) | Ampicillin + gentamicin (or cefotaxime) | GBS, E. coli, Listeria |
| Children (1 mo – 18 yr) | Vancomycin + ceftriaxone ± dexamethasone | N. meningitidis, S. pneumoniae |
| Adults (18–50 yr) | Vancomycin + ceftriaxone | S. pneumoniae (including resistant), N. meningitidis |
| Adults > 50 / immunocompromised | Vancomycin + ceftriaxone + ampicillin | Above + Listeria monocytogenes |
| Post-neurosurgical / VP shunt | Vancomycin + cefepime (or meropenem) | S. aureus, gram-negatives, Pseudomonas |
| Suspected encephalitis | Add acyclovir 10 mg/kg IV q8h | HSV-1 |
For neonates, the regimen is ampicillin plus gentamicin (or ampicillin plus cefotaxime). For children aged 1 month to 18 years, vancomycin plus ceftriaxone is recommended, with dexamethasone added if H. influenzae or S. pneumoniae is suspected. For adults aged 18 to 50, vancomycin plus ceftriaxone provides coverage for resistant S. pneumoniae. For adults over 50 or immunocompromised patients, ampicillin is added to vancomycin and ceftriaxone for Listeria coverage. For post-neurosurgical patients, vancomycin plus cefepime or meropenem provides Pseudomonas coverage.
Adjunctive Dexamethasone
Dexamethasone at 0.15 mg/kg IV every 6 hours for 4 days, given 15 to 20 minutes before or with the first dose of antibiotics, reduces mortality and neurological sequelae in S. pneumoniae meningitis in adults, as demonstrated in the de Gans trial. The benefit is lost if dexamethasone is given after antibiotics. Its use is controversial in resource-limited settings and for non-pneumococcal etiologies. It is recommended in all adults with suspected bacterial meningitis until the causative organism is identified.
Antiviral Therapy
Acyclovir at 10 mg/kg IV every 8 hours should be started empirically in any patient with suspected encephalitis without waiting for HSV PCR results. The duration is 14 to 21 days for confirmed HSV encephalitis. The drug is nephrotoxic, so adequate hydration and renal function monitoring are essential.
Meningococcal Disease
Neisseria meningitidis causes a rapidly progressive illness presenting with fever, a petechial or purpuric rash, and meningismus. It can progress to fulminant purpura (purpura fulminans) and disseminated intravascular coagulation within hours. Droplet precautions are required until 24 hours of effective antibiotic therapy have been administered. Post-exposure prophylaxis for close contacts consists of ciprofloxacin 500 mg PO once for adults, rifampin 600 mg PO every 12 hours for 2 days, or ceftriaxone 250 mg IM once.
Special Considerations
Neonatal meningitis presents with nonspecific symptoms including irritability, poor feeding, temperature instability, and a bulging fontanelle, and LP should always be included in the sepsis workup of ill-appearing neonates. Partially treated meningitis, where prior antibiotic use may sterilize cultures, still shows CSF pleocytosis and chemistry abnormalities, and multiplex PCR is particularly valuable in this setting. Cryptococcal meningitis should be suspected in HIV patients with a CD4 count below 100 and is diagnosed with CSF India ink stain and cryptococcal antigen (CrAg) in CSF and serum. Elevated opening pressure is a hallmark and often requires serial therapeutic LPs.
<image>Comparison of petechial and purpuric skin lesions in meningococcemia, showing progression from small petechiae to confluent purpura fulminans with surrounding tissue necrosis on the lower extremities</image>
Clinical Pearls
Antibiotics should be administered within 1 hour of suspected bacterial meningitis and should never be delayed for CT or LP. The classic triad of fever, neck stiffness, and altered mental status is present in fewer than half of patients, so meningitis should always be considered in the undifferentiated febrile headache patient. IV acyclovir should be started empirically in any patient with altered mental status and fever pending HSV PCR results. CSF multiplex PCR panels have transformed the diagnostic approach by providing rapid pathogen identification. Dexamethasone must be given before or with the first dose of antibiotics to be effective.
References
- van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect. 2016;22(Suppl 3):S37-S62.
- Hasbun R, Abrahams J, Jekel J, et al. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med. 2001;345(24):1727-1733.
- de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549-1556.
- Tyler KL. Acute viral encephalitis. N Engl J Med. 2018;379(6):557-566.
