Can monoclonal antibodies (mAbs) cause aseptic meningitis?

Monoclonal Antibodies and Aseptic Meningitis

Yes, monoclonal antibodies can cause aseptic meningitis as a documented adverse effect, though it is relatively uncommon. This neurological immune-related adverse event has been reported with various monoclonal antibody therapies and requires prompt recognition and management.

Evidence for Monoclonal Antibody-Induced Aseptic Meningitis

Monoclonal antibody-induced aseptic meningitis has been documented in several contexts:

• Natalizumab has been associated with recurrent aseptic meningitis in multiple sclerosis patients 1
• OKT3, an early murine monoclonal antibody used in transplant recipients, showed a strong association with aseptic meningitis development within 72 hours of administration 2
• Intrathecal monoclonal antibodies like HMFG1 have caused aseptic meningitis in 4/7 patients in a study of carcinomatous meningitis 3
• Bispecific antibodies (BsAbs) used in multiple myeloma treatment have been associated with immune effector cell-associated neurotoxicity syndrome, which can include aseptic meningitis 4

Clinical Presentation

Patients with monoclonal antibody-induced aseptic meningitis typically present with:

• Headache (often severe)
• Neck stiffness/nuchal rigidity
• Photophobia
• Fever
• Nausea and vomiting
• Lethargy 4, 5

Diagnostic Approach

When aseptic meningitis is suspected in a patient receiving monoclonal antibody therapy:

1. Neuroimaging: MRI brain with and without contrast to rule out other causes and check for leptomeningeal enhancement 4

2. Lumbar puncture with CSF analysis:

   • Cell count and differential (typically shows lymphocytic pleocytosis)
   • Protein (typically elevated)
   • Glucose (usually normal)
   • Gram stain and cultures (negative for bacteria)
   • Viral PCR panel
   • Cytology to rule out leptomeningeal metastasis
   • Fungal cultures and stains 4, 5

3. Rule out other causes:

   • Infectious meningitis (bacterial, viral, fungal)
   • Carcinomatous meningitis
   • Other drug-induced meningitis (NSAIDs, antibiotics) 5, 6

Management

Management depends on severity but follows these principles:

1. For mild symptoms (Grade 1):

   • May continue monoclonal antibody therapy with close monitoring
   • Symptomatic treatment with analgesics and antipyretics 4

2. For moderate symptoms (Grade 2):

   • Hold monoclonal antibody therapy
   • Consider oral prednisone 0.5-1 mg/kg/day once infection is ruled out
   • Neurological consultation 4

3. For severe symptoms (Grade 3-4):

   • Permanently discontinue the monoclonal antibody
   • Hospitalization
   • IV methylprednisolone 1-2 mg/kg/day
   • Consider pulse steroids (methylprednisolone 1g IV daily for 3-5 days) for severe cases
   • Neurology consultation 4

4. Supportive care:

   • Pain management
   • Adequate hydration
   • Rest 5

Prognosis

The prognosis for monoclonal antibody-induced aseptic meningitis is generally favorable:

• Most cases are self-limited and resolve within 24-72 hours after discontinuation of the causative agent
• Typically resolves without long-term sequelae 5
• However, neurologic immune-related adverse events have higher fatality rates than many other immune-related adverse events, warranting careful monitoring 4

Important Considerations

• The timing of symptom onset is often within days to weeks of monoclonal antibody administration
• Recurrent episodes may occur with repeated administration of the same agent
• Patients with a history of monoclonal antibody-induced aseptic meningitis may be at higher risk with subsequent doses
• Cross-reactivity between different monoclonal antibodies is possible but not universal 1, 2

When evaluating a patient on monoclonal antibody therapy with meningeal symptoms, maintain a high index of suspicion for drug-induced aseptic meningitis while thoroughly ruling out infectious causes before initiating corticosteroid therapy.