EBOLA HEMORRHAGIC FEVER ENCEPHALITIS: EPIDEMIOLOGY, NEUROBIOLOGY, NEUROPATHOLOGY, CLINICAL MANIFESTATIONS, DIAGNOSIS, MANAGEMENT, AND FUTURE DIRECTIONS—DESCRIPTIVE REVIEW

Akwue Tochukwu Anthony*, Nwutobo Chidimma Rhoda

Background: Ebola virus disease (EVD) is a severe zoonotic infection caused by members of the family Filoviridae and remains one of the most lethal viral hemorrhagic fevers affecting humans. Although historically recognized for its systemic manifestations, increasing evidence demonstrates significant neurological involvement during both acute infection and long-term survivorship. Ebola hemorrhagic fever encephalitis has emerged as an important contributor to morbidity, mortality, and chronic disability among affected individuals. Objective: This descriptive review synthesizes current evidence regarding the epidemiology, virology, neurobiology, neuropathology, clinical manifestations, diagnosis, management, prognosis, and future directions of Ebola hemorrhagic fever encephalitis. Methods: A comprehensive literature review was conducted using PubMed/MEDLINE, Web of Science, and Google Scholar databases covering publications from 2010 through 2026. Additional landmark studies published before 2010 were included when relevant. Articles addressing neurological manifestations, central nervous system invasion, neuroimmunology, neuropathology, diagnosis, treatment, survivor outcomes, and public health implications were reviewed and synthesized narratively. Results: Accumulating evidence indicates that Ebola virus possesses significant neuroinvasive potential. Neurological manifestations range from headache, encephalopathy, seizures, and meningoencephalitis during acute infection to persistent cognitive dysfunction, neuropsychiatric disorders, movement abnormalities, neuropathic pain, visual impairment, and chronic post-Ebola neurological syndrome among survivors. Current evidence supports a multifactorial pathogenesis involving direct viral neuroinvasion, blood-brain barrier disruption, endothelial dysfunction, neuroinflammation, microglial activation, cerebrovascular injury, and persistent viral reservoirs within immune-privileged compartments. Advances in molecular diagnostics and monoclonal antibody therapies have improved survival; however, substantial neurological morbidity persists among survivors. Conclusions: Ebola hemorrhagic fever encephalitis represents a major but historically underrecognized component of Ebola virus disease. Recognition of its neuroinfectious and neuroinflammatory characteristics has fundamentally altered understanding of Ebola pathogenesis and survivorship. Future efforts should prioritize early diagnosis, neurological surveillance, biomarker development, rehabilitation services, and investigation of persistent viral reservoirs to reduce long-term neurological disability and improve outcomes among survivors.