This multicenter, observational, and prospective study was based on seven cities in Colombia. Newly diagnosed subjects with encephalitis who fulfilled the International Encephalitis Consortium criteria for possible encephalitis and had no identifiable etiology by an available standard clinical workup were recruited from February 2016 to June 2023. Blood, urine, and cerebrospinal fluid samples were used for standard laboratory work-up and investigation of arboviral infections.

Sixty-two cases were included during the study period. The frequency of encephalitis was higher in 2016, chronologically related to the Zika virus outbreak. Forty-two (66%) patients were male with a median (IQR) age of 42 (19-57) years. The participant’s age exhibited a bimodal distribution that peaked in the second and sixth decades of life. Preceding viral prodromes were frequent (95%) and mostly occurred in the seven days preceding the neurological symptoms (77%). Serologic and molecular testing revealed potential etiologies like Zika virus (n=4), Dengue virus (n=2), flavivirus (n=5), and anti-NMDAR antibodies (2 of 55 sera, 2 of 32 CSF tested). At inclusion, 23 cases (37%) had a modified Rankin Scale of 5, and 16 (26%) developed respiratory failure.