Significant variability exists in current diagnostic and management decisions of patients with aseptic meningitis. Much of the existing confusion in management stems from the use of a diagnostic taxonomy ("aseptic meningitis") that facilitates discharge coding and case reporting, rather than a clinical taxonomy classifying patients according to clinical presentation, at the initial physician encounter. Meningitis with a non-diagnostic CSF Gram stain or "enigmatic meningitis" is what physicians encounter prospectively and encompasses many treatable etiologies (including bacterial meningitis with negative Gram stains, TB, fungal disease, syphilis, HIV, CNS space occupying lesions, as well as endocarditis). In a preliminary retrospective evaluation, we have found that enigmatic meningitis often has a specific etiology and physicians frequently overutilize diagnostic technologies, empiric antimicrobials as well as hospital admissions. Therefore, a rigorous prospective evaluation of patients with the enigmatic meningitis syndrome is needed to develop clinical guidelines that would reduce current diagnostic and therapeutic management variability. The focus of this proposal is to identify and follow a pilot cohort of patients presenting with community acquired enigmatic meningitis (fever, meningeal symptoms, CSF pleocytosis, and negative CSF Gram stain) in the two emergency rooms serving New Haven, Connecticut (Yale-New Haven Hospital and The Hospital of St. Raphael). Our immediate aim will be to describe and analyze clinical outcomes ( neurologic morbidity, mortality, spectrum of defined diagnoses), physician management outcomes (proportions of patients who are hospitalized, undergo cranial imaging, and are empirically treated with antimicrobial agents), and costs. The analytical element of this pilot study will be to identify, in bivariate and multivariable analyses, key sociodemographic, clinical, and paraclinical variables that are associated with the three physician management outcomes. Our ultimate aim will be to expand the study to a larger, more sociodemographically diverse, cohort to develop a clinical index of independent variables that predict which management decisions most benefit patient outcome. The long term goal will be to develop clinical guidelines that clarify management decisions at presentation, and reduce unnecessary costs for this common clinical dilemma.