David Acero-Garces1, Susana Dominguez Penuela1, Beatriz Parra2, Lyda Osorio2, Martha Moyano2, Jairo Lizarazo Niño3, Jorge Angarita4, Jose Vargas Manotas5, Jorge Jimenez6, Reydmar Lopez6, Guillermo Gonzalez-Manrique7, Christian Rojas Cerón8, Juan Rojas9, Fernando Rosso10, Viviana Martinez11, Jonathan Urrego12, Federico Silva13, Catalina Vallejo11, Cindy L. Beltran14, Jaime Quintero2, Julie Benavides15, Daniela Zuluaga Lotero2, Jose Enciso2, Katherine Claros14, Thanya Lagos11, Maria Fernanda Ramos Sanchez3, Jenny Garzon13, Diego Lizarazo Ortega3, Carlos Pardo-Villamizar1
1Johns Hopkins University School of Medicine, 2Universidad del Valle, 3Hospital Universitario Erasmo Meoz, 4Clinica Medilaser, 5Universidad Simon Bolivar, 6IPS Universitaria sede Clínica León XIII, 7Universidad Surcolombiana, 8Universidad del Valle, Clinica Imbanaco, 9Fundación Clínica Infantil Club Noel, 10Fundacion Valle Del Lili, 11Hospital Universitario Departamental de Nariño, 12Hospital Universitario del Valle, 13Fundacion Cardiovascular De Colombia, 14Hospital Universitario de Neiva, 15Universidad Cooperativa de Colombia
Objective:
To characterize the epidemiological, clinical, and laboratory features of cases of encephalitis of unknown etiology included in the NEAS cohort.
Background:
Despite advances in diagnostic methods, many cases of encephalitis are left without an etiological diagnosis, especially in resource-limited settings. The Neuroinfections Emerging in the Americas Study (NEAS) Network was established in Colombia after the Zika virus epidemic in 2015-2016 to investigate the role of emerging infections in neuroinflammatory diseases.
Design/Methods:
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.
Results:
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.
Conclusions:
Endemic viral infections and autoimmune etiologies of encephalitis should be considered when routine laboratory investigations yield no etiology. Future studies on encephalitis should focus on the development of point-of-care or easy-to-deploy molecular and immunological assays for improving the diagnosis of autoimmune and infectious encephalitis in areas with limited resources.