Aseptic meningitis

Aseptic meningitis is defined as meningeal inflammation – i.e. cerebrospinal fluid (CSF) pleocytosis ≥ 5 cells/mm3 – not related to an infectious process. Etiologies of aseptic meningitis can be classified in three main groups: (i) systemic diseases with meningeal involvement, which include sarcoidosis, Behçet's disease, Sjögren's syndrome, systemic lupus erythematosus and granulomatosis with polyangiitis; (ii) drug-induced aseptic meningitis, mostly reported with non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics (sulfamides, penicillins), intravenous immunoglobulin, and monoclonal antibodies; (iii) neoplastic meningitis, either related to solid cancer metastasis (breast cancer, lung cancer, melanoma) or malignant hemopathy (lymphoma, leukemia). Most series in the literature included groups of meningitis that are not stricto sensu aseptic, but should rather be included in the differential diagnosis: (i) infectious meningitis related to virus, parasites, fungi, or fastidious bacteria that require specific diagnostic investigations; (ii) bacterial meningitis with sterile CSF due to previous antibiotic administration, and (iii) parameningeal infections associated with meningeal reaction. Despite progress in microbiological diagnosis (including PCR, and next generation sequencing), and identification of a growing panel of autoimmune or paraneoplastic neurological syndromes, up to two thirds of aseptic meningitis cases are of unknown etiology, finally labeled as ‘idiopathic’. Description of new entities, such as the syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) may decrease the proportion of idiopathic aseptic meningitis. This state-of-the-art review summarizes the characteristics of main causes of aseptic meningitis.