A diverse group of noninfectious processes can mimic infection in the central nervous system (CNS). Clinical manifestations primarily take the form of a chronic meningitic syndrome. They usually present with subacute onset, headache, fever, and stiff neck. Encephalitic signs also can occur, and seizures are not uncommon. CSF is marked by elevated protein, decreased glucose, and usually lymphocytic pleocytosis.

Most authors define chronic meningitis as the persistence of these signs and symptoms with abnormal CSF for at least 4 weeks.199 This is distinguished from acute meningitis, with symptoms of less than 2 weeks’ duration, and recurrent meningitis, defined as at least two clinically similar episodes with an interval of clinical and CSF normalization. Noninfectious processes can cause meningitis of all three types:199

Acute meningitis:

  • drugs
  • systemic lupus erythematosus (SLE)

Recurrent meningitis:

  • Mollaret’s meningitis
  • systemic lupus erythematosus (SLE)
  • tumor
  • migraine

Chronic meningitis:

  • Behçet’s disease
  • leptomeningeal metastases
  • primary central nervous system angiitis
  • systemic lupus erythematosus (SLE)
  • Sjögren’s syndrome

Seizures, although not causing an acute meningitis syndrome, can by themselves cause a mild postictal CSF pleocytosis. CSF glucose and protein are normal. Cell counts usually normalize within one week.200

Mollaret's meningitis

Mollaret’s meningitis is a rare syndrome characterized by recurrent episodes of aseptic meningitis. Symptoms resolve spontaneously within days, only to recur weeks to months later. Recurrences can go on for years, then cease as suddenly and inexplicably as they began. Recent studies have shown a possible link with herpes simplex virus (HSV).199

Each episode of Mollaret’s meningitis presents fulminantly with high fever, severe headache, and meningitic signs. Focal and generalized seizures can be an unpredictable component of each episode. Although this disorder is most commonly seen in young adults, the age range is potentially wide.

Lumbar puncture reveals a neutrophilic and lymphocytic pleocytosis. Protein is mildly elevated and glucose is usually normal. The CSF generally normalizes by 1 week.

Behçet’s disease

Behçet’s disease is a systemic inflammatory disease characterized by recurrent oral and genital aphthous ulcers, uveitis, and skin lesions. CNS involvement occurs in up to 29% of cases, manifested by aseptic meningitis, meningoencephalitis, cranial nerve palsies, and seizures.

There is no specific diagnostic test for Behçet’s disease; instead, diagnostic criteria have been established. MRI reveals small foci of high-signal activity on T2 images. CSF shows a mild pleocytosis.

Immunosuppressive therapy has been used in Behçet’s disease affecting the CNS. Cytotoxic agents, such as chlorambucil or cyclophosphamide, are added to glucocorticoid therapy to improve results. Comorbid seizure management is routine.

Inflammatory disorders

Inflammatory noninfectious causes of encephalitis and meningitis with potential seizure comorbidity include SLE, Sjögren’s syndrome, primary CNS angiitis, and sarcoidosis. These are discussed fully elsewhere.

Adapted from: Seiden L and Krumholz A. Inflammatory noninfectious disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;135–154. 
With permission from Elsevier (www.elsevier.com). 

Reviewed By: 
Steven C. Schachter, MD
Sunday, February 29, 2004