RESUMO
Background: Arboviruses are RNA viruses and some have the potential to cause neuroinvasive disease and are a growing threat to global health. Objectives: Our objective is to identify and map all aspects of arbovirus neuroinvasive disease, clarify key concepts, and identify gaps within our knowledge with appropriate future directions related to the improvement of global health. Methods: Sources of Evidence: A scoping review of the literature was conducted using PubMed, Scopus, ScienceDirect, and Hinari. Eligibility Criteria: Original data including epidemiology, risk factors, neurological manifestations, neuro-diagnostics, management, and preventive measures related to neuroinvasive arbovirus infections was obtained. Sources of evidence not reporting on original data, non-English, and not in peer-reviewed journals were removed. Charting Methods: An initial pilot sample of 30 abstracts were reviewed by all authors and a Cohen's kappa of κ = 0.81 (near-perfect agreement) was obtained. Records were manually reviewed by two authors using the Rayyan QCRI software. Results: A total of 171 records were included. A wide array of neurological manifestations can occur most frequently, including parkinsonism, encephalitis/encephalopathy, meningitis, flaccid myelitis, and Guillain-Barré syndrome. Magnetic resonance imaging of the brain often reveals subcortical lesions, sometimes with diffusion restriction consistent with acute ischemia. Vertical transmission of arbovirus is most often secondary to the Zika virus. Neurological manifestations of congenital Zika syndrome, include microcephaly, failure to thrive, intellectual disability, and seizures. Cerebrospinal fluid analysis often shows lymphocytic pleocytosis, elevated albumin, and protein consistent with blood-brain barrier dysfunction. Conclusions: Arbovirus infection with neurological manifestations leads to increased morbidity and mortality. Risk factors for disease include living and traveling in an arbovirus endemic zone, age, pregnancy, and immunosuppressed status. The management of neuroinvasive arbovirus disease is largely supportive and focuses on specific neurological complications. There is a need for therapeutics and currently, management is based on disease prevention and limiting zoonosis.
RESUMO
Neurotropic viruses are a threat to human populations due to ongoing zoonosis. A wide array of neurological manifestations can occur most often including parkinsonism, encephalitis/encephalopathy, flaccid myelitis, and Guillain-Barré syndrome. Neuroinvasion occurs through: transneural transmission, blood brain barrier (BBB) dysfunction, and 'trojan horse' mechanism or infected immune cell trafficking into the central nervous system (CNS). Transneural transmission occurs through virus mediated hijacking of intracellular transport proteins allowing retrograde viral transport. BBB dysfunction occurs through cytokine storm increasing membrane permissibility. Increased chemokine expression allows leukocyte trafficking to the BBB. Virally infected leukocytes may successfully pass through the BBB allowing the pathogen to infect microglia and other CNS cell types. We define cerebrospinal fluid (CSF) nondetection as a virus' ability to evade direct CSF detection but still causing significant neurological symptoms and disease. Mechanisms of CSF nondetection include: transneuronal propagation through trans-synaptic transmission, and synaptic microfusion, as well as intrathecal antibody synthesis and virus neutralization. Direct virus detection in CSF is associated with an increased neurological disease burden. However, the lack of CSF detection does not exclude CNS involvement due to possible neuroevasive mechanisms.
