Neurologic consequences of arbovirus infections: New challenges

Abstract

Arbovirus includes several families of viruses that are spread by arthropod vectors, most commonly mosquitoes, ticks, and sand flies. The families of viruses included in the arbovirus group are Flaviviridae, Togaviridae, Bunyaviridae, and Reoviridae. These large families of viruses have a common feature, an RNA genome that allows these viruses to rapidly adapt to ever-changing host and environmental conditions. The arbovirus infections are associated with a wide spectrum of neurologic manifestations, we review mainly dengue, chikungunya and Zika infections that have rapidly expanded their geographic distribution. Dengue is the most widespread arboviral disease, with an estimated 70–140 million cases occurring annually. Neurological dengue is classified as a form of Severe Dengue. Neurologic involvement occurs in 4%–5% of confirmed dengue cases (Puccioni-Sohler et al., 2009). The main neurologic manifestations are: encephalitis, meningitis, myelitis and Guillain Barre syndrome. Associated neurologic clinical manifestations of chikungunya virus include: meningoencephalitis, seizures, Guillain-Barre syndrome, myelopathy, encephalomyeloradiculitis and neuropathies (Samra et al., 2017) On February 1st, 2016 the World Health Organization (WHO) declared Zika virus infection an international public health emergency due to 2015 reports from Brazil of cluster of microcephaly cases and other neurological disorders , following a cluster of Guillain Barre Syndrome cases in French Polynesia in 2014 (Miranda-Filho Dde et al., 2016; Cao-Lormeau et al., 2016). The Zika virus (ZIKV) infection represents a major global health problem. By 2017 the WHO estimated that nearly 100 million people, and more than 1 million pregnant women in the Americas, were infected, suggesting that tens of thousands of children may have had the congenital ZIKV syndrome (Aragao et al., 2017; Lebov et al., 2019). The ZIKV infection mainly the Asian lineage, has a neurotropism with a wide spectrum of neurologic consequences and represent neuropathological agent with several neurological complications. The neurologic spectrum of Zika virus (ZIKV) infection includes: 1) Congenital Zika Syndrome by affecting the neural stem cells of the human fetal brain (Mlakar et al., 2016); 2) Guillain-Barré Syndrome by an autoimmune response against peripheral myelin and/or axonal components or probable direct inflammatory reaction (Cao-Lormeau et al., 2016); 3) Sensory neuropathy by infecting directly the peripheral neurons and causing substantial cell death and pathogenic transcriptional dysregulation (Oh et al., 2017; Medina et al., 2016); 4) Encephalitis/meningoencephalitis and myelitis by a direct viral inflammatory process on the central nervous system; 5) Acute Disseminated Encephalomyelitis and optic neuropathy; 6) Seizures and Epilepsy; 7) Childhood arterial ischemic stroke by probable inflammatory reaction and endothelial injury. The Zika, Dengue and Chikungunya arbovirus infections and its neurologic consequences represent a major global health problem [1] Aragao MFVV, Holanda AC, Brainer-Lima AM, et al. Nonmicrocephalic Infants with congenital Zika syndrome suspected only after neuroimaging evaluation compared with those with microcephaly at birth and postnatally: how large is the Zika virus "Iceberg"? AJNR Am J Neuroradiol. 2017 Jul;38(7):1427-1434. [2] Cao-Lormeau VM, Blake A, Mons S, Lastère S, et al. Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016 Apr 9;387(10027):1531-1539. [3] Lebov JF, Arias JF, Balmaseda A, et al. International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol. BMC Pregnancy Childbirth. 2019 Aug 7;19(1):282 [4] Medina MT, England JD, Lorenzana I, Medina-Montoya M, et al Zika virus associated with sensory polyneuropathy. J Neurol Sci. 2016 Oct 15;369:271-2. [5] Miranda-Filho D de B, Martelli CM, Ximenes RA, et al.. Initial description of the presumed congenital Zika syndrome. Am J Public Health. 2016 Apr;106(4):598-600. [6] Mlakar J, Korva M, Tul N,et al. Zika virus associated with microcephaly. N Engl J Med. 2016 Mar 10;374(10):951-8. [7] Oh Y, Zhang F, Wang Y, et al. Zika virus directly infects peripheral neurons and induces cell death. Nat Neurosci. 2017 Sep;20(9):1209. [8] Puccioni-Sohler M, Soares CN, Papaiz-Alvarenga R, et al. Neurologic dengue manifestations associated with intrathecal specific immune response. Neurology. 2009 Oct 27;73(17):1413-7. [9] Samra JA, Hagood NL, Summer A, Medina MT, et al. Clinical features and neurologic complications of children hospitalized with Chikungunya virus in Honduras. J Child Neurol. 2017 Jul;32(8):712-716.