Viral Parkinsonism: An underdiagnosed neurological complication of Dengue virus infection

Abstract

Dengue virus (DENV) is a flavivirus that is a significant cause of human disease costing billions of dollars per year in medical and mosquito control costs. It is estimated that up to 20% of DENV infections affect the brain. Incidence of DENV infections is increasing, which suggests more people are at risk of developing neurological complications. The most common neurological manifestations of DENV are encephalitis and encephalopathy, and movement disorders such as parkinsonism have been observed. Parkinsonism describes syndromes similar to Parkinson’s Disease where tremors, stiffness, and slow movements are observed. Parkinsonism caused by viral infection is characterized by patients exhibiting at least two of the following symptoms: tremor, bradykinesia, rigidity, and postural instability. To investigate DENV-associated parkinsonism, case studies and reports of DENV-associated parkinsonism were obtained from peer-reviewed manuscripts and gray literature. Seven reports of clinically diagnosed DENV-associated parkinsonism and 15 cases of DENV encephalitis, where the patient met the case criteria for a diagnosis of viral parkinsonism were found. Clinically diagnosed DENV-associated parkinsonism patients were more likely to be male and exhibit expressionless face, speech problems, and lymphocytosis. Suspected patients were more likely to exhibit tremor, have thrombocytopenia and low hemoglobin. Viral parkinsonism can cause a permanent reduction in neurons with consequential cognitive and behavior changes, or it can leave a latent imprint in the brain that can cause neurological dysfunction decades after recovery. DENV-associated parkinsonism is underdiagnosed and better adherence to the case definition of viral parkinsonism is needed for proper management of potential sequalae especially if the patient has an ongoing or potential to develop a neurodegenerative disease. Author summary Dengue Virus (DENV) causes generalized fever in most patients and is transmitted via Aedes aegypti mosquitos. A small proportion of DENV infected patients have neurological complications associated with the critical phase of the illness. The usual neurological manifestations are encephalitis and encephalopathy, but there can also be movement disorders such as parkinsonism. DENV patients with parkinsonism present with tremor, bradykinesia, instability, and rigidity on top of the typical febrile manifestations of the disease. We searched the literature and uncovered 7 cases of clinically diagnosed DENV parkinsonism patients and 15 cases of suspected DENV parkinsonism. We found that the clinically diagnosed patients were more likely to be male, have expressionless face, speech issues and lymphocytosis. The suspected cases often had a diagnosis of encephalitis and were more likely to have tremors, thrombocytopenia, and low hemoglobin.