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.

COVID-19 and neurological disorders: what might connect Parkinson’s disease to SARS-CoV-2 infection

“…Recently, a meta-analysis has shown that the development of parkinsonism may be an underdiagnosed complication of Dengue virus infection. However, also in this case, as for the other viruses mentioned above, there seems to be no data showing an association between an increased risk of developing idiopathic PD and a previous infection by Dengue virus (16). Antigenic mimicry has been hypothesized to explain the increased risk of PD after herpes simplex virus 1 (HSV-1) infection.…”

Central nervous system infections in the tropics

“…Pathophysiology may be direct neuronal invasion or antibody-dependent enhancement [82]. Other syndromes described recently include Parkinsonism [83], myelitis [84] and GBS [85]. Laboratory diagnosis of acute dengue is by demonstration of NS1 antigen or IgM antibodies in serum (IgG can predominate in secondary infection), or by PCR in very early stages of the illness [86].…”

The Contribution of Microglia and Brain-Infiltrating Macrophages to the Pathogenesis of Neuroinflammatory and Neurodegenerative Diseases during TMEV Infection of the Central Nervous System

“…The CNS has a unique and complex structure with a restricted regeneration capacity. The perturbation of the CNS homeostasis, induction of neuroinflammation, neuronal damage, and neuron degeneration often occur as a result of a CNS viral infection and are closely associated with the development of neuroinflammatory and neurodegenerative diseases such as multiple sclerosis (MS) [ 6 , 7 , 8 , 9 , 10 , 11 ], Alzheimer’s [ 10 , 12 , 13 ], epilepsy [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], and others [ 26 , 27 , 28 , 29 , 30 ]. In fact, viral infections are known or suspected to play a role in the onset and progression of various neurological disorders.…”