Diagnostic Approach to Autoimmune and Inflammatory Meningitis

Introduction

• Autoimmune and inflammatory meningitis requires a comprehensive diagnostic approach, including cerebrospinal fluid (CSF) analysis, laboratory tests, imaging studies, and specialized testing, as recommended by the Critical Care Medicine and Journal of Infection guidelines 1, 2

Cerebrospinal Fluid (CSF) Analysis

• In patients with suspected autoimmune or inflammatory meningitis, a cell count with differential may show lymphocytic pleocytosis (5-500 cells/μL), although normal cell count can occur in early disease or immunocompromised patients, according to the Critical Care Medicine guidelines 1
• The CSF/plasma glucose ratio may be reduced but is typically >0.6, unlike bacterial meningitis where it's often <0.36, as recommended by the Journal of Infection guidelines 2
• Gram stain and culture are essential to exclude bacterial infection, as suggested by both Critical Care Medicine and Journal of Infection guidelines 1, 2
• Typical CSF findings in different CNS infections are summarized in the following table:

• The following conditions have typical WBC counts and predominant cell types:

*Note: Early viral meningitis may show neutrophil predominance initially, with a strength of evidence level of moderate 2

• CSF analysis should include measurement of opening pressure, appearance, cell count and differential, protein and glucose levels, Gram stain and culture, and PCR testing for viral pathogens, as recommended by the Centers for Disease Control and Prevention, with a strength of evidence level of high 2

Laboratory Tests

• C-reactive protein (CRP) is typically less elevated than in bacterial meningitis, as noted in the Clinical Infectious Diseases guidelines 4
• Autoimmune serologies, including antinuclear antibodies (ANA), anti-dsDNA, and anti-Ro/La antibodies, can help identify underlying systemic autoimmune diseases 4
• CSF lactate <2 mmol/L can help rule out bacterial disease, and oligoclonal bands should be evaluated to assess for inflammatory/autoimmune processes, with a strength of evidence level of moderate 3

Imaging Studies

• MRI brain with and without contrast is recommended for all patients to look for leptomeningeal enhancement, T2/FLAIR changes, and signs of limbic encephalitis, although no specific citation is provided for this recommendation
• Magnetic resonance imaging (MRI) with contrast is abnormal in over 90% of cases, and cerebral angiography can detect arterial narrowings, occlusions, or aneurysms, with a strength of evidence level of high 5
• MRI brain with and without contrast is recommended, particularly if encephalitis is suspected, and T2/FLAIR changes typical of autoimmune encephalopathies or limbic encephalitis should be looked for, with a strength of evidence level of high 6

Diagnostic Considerations

• Collecting at least 22 mL of CSF can ensure adequate volume for all necessary tests, as suggested by the Journal of Infection guidelines 2
• In cases with focal neurological signs, performing neuroimaging before lumbar puncture can help rule out mass lesions, as recommended by the Journal of Infection guidelines 2
• Overlooking the possibility of partially treated bacterial meningitis, which can mimic autoimmune meningitis, is a common pitfall, as noted in the Journal of Infection guidelines 2
• Don't rule out HSV encephalitis based on normal initial CSF findings, as HSV PCR may be negative early in the disease course, and a second CSF examination 24-48h later is often diagnostic, with a strength of evidence level of high 3
• Don't rely solely on CSF cell count, as CSF protein and glucose should be interpreted in conjunction with clinical presentation, and normal white cell count doesn't exclude CNS infection, especially in immunocompromised patients, with a strength of evidence level of moderate 3
• Don't delay empiric treatment if clinical suspicion for encephalitis is high, as mortality from untreated HSV encephalitis is high, and treatment should not be delayed while awaiting diagnostic confirmation, with a strength of evidence level of high 3

Specialized Testing

• PCR testing for viral pathogens, such as HSV-1, HSV-2, VZV, and enteroviruses, can aid in diagnosis, as suggested by the Journal of Infection guidelines 2
• Storing additional CSF for further specialized testing that may be needed later is a good practice, as recommended by the Journal of Infection guidelines 2
• A viral PCR panel should be tested for HSV-1, HSV-2, VZV, and enteroviruses to aid in diagnosis, as recommended by the Infectious Diseases Society of America, with a strength of evidence level of high 7
• CSF culture should be performed to rule out bacterial infection, with a strength of evidence level of high, according to the Centers for Disease Control and Prevention 3
• Cytology should be performed to rule out leptomeningeal malignancy, and an autoimmune encephalitis panel should be considered, particularly if other causes are not identified, with a strength of evidence level of moderate 6

Treatment

• IV aciclovir (10 mg/kg three times daily) should be started if encephalitis is suspected while awaiting PCR results, with a strength of evidence level of high, according to the Infectious Diseases Society of America 7
• Empiric antibiotics should only be considered if clinical suspicion for bacterial meningitis is high despite CSF findings, with a strength of evidence level of moderate, according to the American Academy of Neurology 3
• If aseptic meningitis is suspected, IT corticosteroids (4 mg IT dexamethasone) should be considered if drug-induced, and the offending medication should be discontinued if identified, with a strength of evidence level of moderate, according to the European Society for Medical Oncology 8