What is aseptic meningitis?

Aseptic Meningitis

Aseptic meningitis is a syndrome characterized by acute onset of meningeal symptoms, fever, and cerebrospinal fluid pleocytosis with bacteriologically sterile cultures. 1

Definition and Clinical Characteristics

Aseptic meningitis is defined by:

• Symptoms of meningism (headache, neck stiffness, photophobia)
• Fever
• Cerebrospinal fluid (CSF) pleocytosis (increased white blood cells)
• Bacteriologically sterile CSF cultures
• No evidence of bacterial or fungal meningitis 1

The clinical presentation typically includes:

• Acute onset headache
• Nuchal rigidity (stiff neck)
• Photophobia
• Fever
• Nausea and vomiting
• Lethargy 1, 2

Etiology

Aseptic meningitis is a syndrome of multiple etiologies, with the most common causes being:

1. Viral infections (most common cause):

   • Enteroviruses (Coxsackie and ECHO viruses) account for more than half of all cases 3
   • Other viruses: herpes simplex virus, varicella-zoster virus, mumps, HIV

2. Drug-induced aseptic meningitis (DIAM):

   • Intrathecal administration of chemotherapeutics (methotrexate, cytarabine, cisplatin) 1
   • Systemic medications through immunologic hypersensitivity:
     • Non-steroidal anti-inflammatory drugs (NSAIDs), especially ibuprofen
     • Antimicrobials
     • Intravenous immunoglobulins
     • Monoclonal antibodies and immune checkpoint inhibitors 4, 5, 6

3. Other causes:

   • Partially treated bacterial meningitis
   • Fungal or parasitic infections
   • Malignancy
   • Autoimmune disorders
   • Systemic illness 3

Diagnosis

The diagnosis of aseptic meningitis relies on:

1. Cerebrospinal fluid analysis (essential):

   • Pleocytosis (increased white blood cells)
   • Elevated protein levels
   • Normal glucose levels
   • Negative bacterial and fungal cultures 1

2. Neuroimaging:

   • MRI of the brain with and without contrast may be indicated to rule out other causes 4

3. Additional testing to identify specific etiology:

   • PCR for viral pathogens in CSF
   • Serology for specific infectious agents
   • Drug history to identify potential causative medications 2, 5

Differential Diagnosis

Important conditions to rule out include:

• Bacterial meningitis (medical emergency requiring prompt antibiotics)
• Fungal meningitis
• Tuberculous meningitis
• Parameningeal infections
• Encephalitis (particularly herpes simplex encephalitis)
• Lyme disease
• Malignancy 2, 7

Management

Treatment is primarily supportive for most cases of viral aseptic meningitis:

1. Supportive care:

   • Pain management
   • Antipyretics
   • Adequate hydration
   • Rest 2, 3

2. For drug-induced aseptic meningitis:

   • Discontinuation of the suspected causative agent
   • Symptoms typically resolve within 24-72 hours after drug discontinuation 5, 6

3. For immune checkpoint inhibitor-induced aseptic meningitis:

   • Corticosteroid therapy (methylprednisolone 1-4 mg/kg/day) may be considered
   • Decision to continue, hold, or permanently discontinue immunotherapy depends on severity 4

4. For chemotherapy-induced aseptic meningitis:

   • Concomitant use of intrathecal corticosteroids (4 mg intrathecal dexamethasone) may help prevent aseptic meningitis 1

Prognosis

The prognosis for aseptic meningitis is generally favorable:

• Most cases of viral meningitis are self-limited with complete recovery
• Drug-induced aseptic meningitis typically resolves without long-term sequelae after discontinuation of the offending agent 2, 6

Important Considerations

• Bacterial meningitis must be ruled out before confirming aseptic meningitis, as delayed antibiotic treatment can worsen mortality
• Empiric antibiotics should be started promptly when bacterial meningitis cannot be excluded immediately
• Clinical findings alone are unreliable to differentiate bacterial from aseptic meningitis
• Drug-induced aseptic meningitis should be suspected when symptoms develop shortly after drug initiation or rechallenge 2, 5