Pathophysiology and Clinical Implications of Dengue-Associated Neurological Disorders

Ramtin Naderian^1,2Elham Paraandavaji³Amir Hossein Maddah¹Saeedeh Keshavarzi¹Anoosha Habibian¹Rayan Naderian⁴Seyed Mohammad Hosseini⁵Valentyn Oksenych^6,7,8*Majid Eslami^9*

• ¹Universal Scientific Education and Research Network (USERN), Semnan, Iran, Semnan, Iran
• ²Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Semnan, Iran
• ³Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Tehran, Iran
• ⁴Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
• ⁵Department of Pediatrics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran, Semnan, Iran
• ⁶University of Bergen, 5020 Bergen, Norway, Bergen, Norway
• ⁷Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway, Trondheim, Norway
• ⁸Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden, Huddinge, Sweden
• ⁹Department of bacteriology and Virology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran, Semnan, Iran

Dengue virus (DENV), a mosquito-borne Flavivirus, represents a growing global health challenge, particularly in tropical and subtropical regions. The 2009 WHO classification system for dengue categorizes infections into dengue without warning signs, dengue with warning signs, and severe dengue. This framework highlights the diverse clinical presentations and supports more efficient triage and management of cases. The neurological effects of DENV infection, which include direct neuroinvasion, systemic problems, and immune-mediated sequelae, are a less well-studied but nevertheless important consequence. Guillain-Barré syndrome, acute disseminated encephalomyelitis, myelitis, meningitis, and encephalitis are important neurological symptoms. The dengue classification system improves clinical management by dividing cases into dengue without warning signs, dengue with warning signs, and severe dengue. Mild cases show fever with symptoms like headache and rash, while warning signs include abdominal pain, persistent vomiting, bleeding, and lab changes indicating higher risk. Severe dengue is characterized by critical complications such as shock, severe bleeding, or organ failure. Improved diagnostics aid early detection, and new treatments targeting viral replication and inflammation are being explored alongside supportive care. Although there are still challenges in reaching the ideal vaccination coverage, the introduction of potent vaccines like Dengvaxia and Qdenga provide an achievable option for prevention. Thorough study into DENV's neurological effects and treatment options is essential as the virus's geographic range is increased by climate change and international travel. Reducing the worldwide burden of dengue-related neurological complications requires addressing the intricate interactions between virological, immunological, and environmental variables.