Neurological Manifestations in Adult Survivors of Ebola Virus Disease.

Importance: Ebola virus disease (EVD) causes multiorgan damage and is highly fatal. EVD's neurological impact among survivors remains poorly characterized due to limited neurological assessment capabilities in the remote regions where most outbreaks occur. Objective: To characterize neurological sequelae in EVD survivors over more than 7 years' longitudinal follow-up. Design, Setting, and Participants: Under the Ebola Natural History Study (PREVAIL III; PIII), the Neurology Study of PIII was a prospective longitudinal cohort study in Liberia of adult Ebola survivors and control individuals conducted from September 2015 to March 2023 at the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) site at John F. Kennedy Medical Center in Monrovia, Liberia. Data were analyzed from April 2023 to September 2025. Exposures: Neurological evaluations were performed by trained neurologists biannually. Questionnaire and neurological examination data were collected on case report forms. Main Outcomes and Measures: Neurological symptom prevalence and neurological examination scores were compared to those of control individuals. Tests for differences between survivors and control individuals were conducted using generalized linear mixed-effects models controlling for age and sex. Overdispersed Poisson models were used to test for computed neurological examination score differences. Neurological examination scores were developed for this study, representing the cumulative abnormalities on neurological examinations, denoted on standardized case report forms, with the general neurological examination score representing all examination abnormalities and the central nervous system score representing the central nervous system-specific abnormalities on examination. Results: Analysis after serologic testing included 148 Ebola antibody-positive survivors (mean [SD] age, 34.8 [10.5] years; 74 [50%] female) and 81 antibody-negative contacts (mean [SD] age, 35.8 [12.6] years; 41 [51%] female). During acute infection, survivors reported headaches, altered mental status, and strokelike symptoms or meningoencephalitis (rarely). Survivors had significant neurological sequelae involving the entire neuraxis: cognitive dysfunction (83 [56.1%]), persistent headaches (98 [66.2%]), sleep abnormalities (40 [27.0%]), depression (73 [49.3%]), sexual dysfunction (48 [32.4%]), tremor (18 [20.3%]), fatigue (71 [51.1%]), cranial nerve abnormalities (60 [40.5%]), and sensory abnormalities (45 [30.4%]). Over 7 years' follow-up, most survivors demonstrated improvement in neurological status. The final visit included 115 survivors (77.7%) and 61 close contacts (75.3%). Persistent symptoms at final evaluation in survivors compared to contacts were memory loss (66 [57.4%] vs 16 [26.2%], respectively; P < .001), irritability (42 [36.5%] vs 9 [14.8%], respectively; P = .006), and trouble concentrating (34 [29.6%] vs 6 [9.8%], respectively; P = .002). Conclusions and Relevance: The findings indicate that Ebola virus infection is associated with neurological complications in survivors, with increased health care burden and socioeconomic consequences. These neurological issues generally improved with time, but some persisted long-term. Close neurological follow-up of EVD survivors may be warranted.