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.