Meningitis & Encephalitis

Acute Bacterial Meningitis

Streptococcus pneumoniae and Neisseria meningitidis are responsible for 80% of all cases of acute bacterial meningitis in adults. Immunocompromised patients have a higher likelihood of fungal, other bacterial, or tuberculous meningitis. In particular, Listeria monocytogenes should be considered as a possible pathogen in patients who are pregnant or older than 50 and in those with impaired cell-mediated immunity due to chronic illness, organ transplantation, HIV, malignancy, or immunosuppressive therapy. Nonbacterial causes of meningitis (aseptic meningitis), often caused by viral infections, are common. However, any patient with suspected meningitis must be presumed to have bacterial meningitis until proven otherwise by urgent lumbar puncture (LP), empiric antibiotics (see table below), and glucocorticoids, if indicated.

Presentation

The majority of patients with acute bacterial meningitis present with two of the following four symptoms:

• headache

• fever

• nuchal rigidity

• altered mental status (a score <14 on the Glasgow Coma Scale)

Diagnosis

• history and physical examination: Pay specific attention to immunocompromised state (HIV, transplant recipient, medications, etc.), age, sick contacts, and recent travel.

• workup: This includes lumbar puncture with opening pressure, cerebrospinal fluid (CSF) analysis (total protein, glucose, cell count, and differential), CSF gram stain and culture, and relevant polymerase chain reaction (PCR) studies (see table below for analysis and interpretation of CSF).

  • Attempt to obtain LP as soon as possible to avoid a sterilized CSF, which can lead to a false-negative result.

• cranial imaging: Typically, head CT is preferred over brain MRI because it is faster and leads to less delay in diagnosis and therapeutic interventions; imaging should precede LP in adult patients with:

  • new-onset seizures

  • immunocompromised state

  • suspicious signs of increased intracranial pressure or space-occupying lesions

  • moderate-to-severe impairment of consciousness

Management

The following algorithm and table summarize management and recommended empiric antimicrobial regimens for treating adults with community-acquired bacterial meningitis. Avoid delay in initiating treatment because it can lead to worse outcomes.

(Source: Community-Acquired Bacterial Meningitis in Adults. N Engl J Med 2006.)

(Source: Community-Acquired Bacterial Meningitis in Adults. N Engl J Med 2006.)

Note: Dexamethasone has been shown to be beneficial in patients with meningitis from S. pneumoniae and should be started in patients suspected of having bacterial meningitis before or concurrent with the first dose of antibiotics. (Read more about dexamethasone treatment for bacterial meningitis in NEJM Journal Watch.)

Nonbacterial or aseptic meningitis is most commonly caused by enteroviruses or herpes simplex virus. (Read more about aseptic meningitis and encephalitis in NEJM Journal Watch.)

Encephalitis

Encephalitis is defined by the Infectious Diseases Society of America (IDSA) as the presence of an inflammatory process of the brain in association with clinical evidence of neurologic dysfunction.

Most infectious cases of encephalitis are caused by viruses, but other infectious causes include bacterial, fungal, protozoal, and helminthic. Additionally, noninfectious causes of encephalitis include autoimmune and paraneoplastic etiologies. However, the etiology of encephalitis is unknown in many patients even after a thorough workup. Therefore, an attempt to identify the cause of encephalitis should be made despite the difficulty and the lack of definitive treatment in many cases.

The clinical presentation of encephalitis is varied and tied to etiology for both infectious and noninfectious types. Successful diagnosis is important for prognosis, prophylaxis, and public health.

Diagnosis

Diagnosis of encephalitis is based on epidemiology, risk factors, clinical features, and diagnostic studies (including CSF, serology, and imaging). The approach to a patient with suspected encephalitis should begin with assessment and stabilization of neurologic emergencies, followed by investigations to determine the likely etiology (e.g., infectious, noninfectious, or autoimmune).

• thorough history and physical exam (including recent febrile illness, travel history, and history of an immunocompromised state)

  • important components in the history and clinical assessment of encephalitis: new-onset altered level of consciousness, seizures, focal CNS findings, memory deficits, and personality or psychiatric disturbances; in particular, autoimmune etiologies may feature these symptoms

• lumbar puncture with CSF analysis

• investigations for infectious cause:

  • laboratory tests and cultures

  • serologic testing for HIV and Epstein-Barr virus (EBV)

  • viral respiratory panel

  • CSF cell counts and cultures with PCR for HSV types 1 and 2, EBV, varicella-zoster virus, West Nile virus, and enteroviruses

  • serum and CSF for cryptococcal antigen if fungi are suspected

• investigations for autoimmune cause:

  • autoantibody testing in serum and CSF; presence in CSF highly suggestive of autoimmune cause

• MRI (use CT only if MRI is unavailable or contraindicated)

• electroencephalogram

• brain biopsy (rarely indicated)

(Source: Acute Encephalitis in Immunocompetent Adults. Lancet 2019.)

The following table summarizes common etiologies of encephalitis and associated CSF and MRI findings:

(Source: Acute Encephalitis in Immunocompetent Adults. Lancet 2019.)

Autoimmune Antibody-Mediated Encephalitis

In addition to infectious causes, encephalitis may be caused by autoimmune antibody-mediated processes. The IgG class of antibody is predominant in these cases. Some of the responsible antibodies and associated syndromes are presented in the table below. Autoimmune encephalitis may present as part of a paraneoplastic syndrome. These patients should be screened for an underlying neoplastic process (e.g., association of ovarian teratomas to N-methyl-D-aspartate (NMDA) receptor-mediated encephalitis).

(Source: Antibody-Mediated Encephalitis. N Engl J Med 2018.)

Treatment

• Infectious encephalitis

  • Treatment options for infectious encephalitis are generally limited beyond supportive care.

  • Acyclovir should be initiated in all patients with suspected encephalitis pending diagnostic tests to cover HSV, which can be life-threatening if not treated rapidly.

  • Doxycycline should be initiated for suspicion of rickettsial or ehrlichial infection, depending on geographic location and season.

  • Consider empiric acute bacterial meningitis treatment (see above).

• Autoimmune encephalitis

  • Systemic immunotherapy forms the basis of treatment. In addition, treating the source of the immunologic response (e.g., the primary tumor in cases of paraneoplastic presentations) has been shown to improve the encephalitis.

  • Systemic glucocorticoids, plasma exchange, and intravenous immunoglobulin (IVIG) therapy have been used with the addition of rituximab for refractory or relapsing cases.