Vice Chair and Associate Professor, Weill Cornell Medical College
Dr. Safdieh reports no financial relationships relevant to this field of study.
SYNOPSIS: Neurologic sequelae of Zika virus infections include Guillain-Barré syndrome, encephalitis, transverse myelitis, and chronic inflammatory demyelinating polyneuropathy.
SOURCE: da Silva IRF, Frontera JA, Bispo de Filippis AM, et al. Neurologic complications associated with Zika virus in Brazilian adults. JAMA Neurol 2017;74:1190-1198.
Zika virus is a mosquito-born flavivirus that has emerged in Central and South America as well as the Caribbean and isolated parts of the United States. Transmission of infection can occur via a bite from an infected mosquito or via direct human-to-human sexual contact. Zika virus is known to cause microcephaly when pregnant women are exposed. However, other neurologic complications, mainly Guillain-Barré syndrome (GBS), have been described in association with Zika virus infections. Most of the reports of GBS and other neurologic complications of Zika in adults are based on retrospective case series.
Brazil encountered many cases of Zika virus infection in a 2015-2016 epidemic, with an estimated number of cases between 500,000-1.5 million nationwide. da Silva et al conducted a prospective, observational study in a single, large tertiary care academic hospital in Rio de Janeiro. The authors evaluated consecutive patients admitted between December 2015 and May 2016, and compared this cohort to a historical cohort in 2013-2014, before Zika virus existed in Brazil. Patients who were included in the analysis presented with a new-onset parainfectious or neuroinflammatory disease. Patients were considered to have recent exposure to Zika virus if rRT-PCR of serum or cerebrospinal fluid (CSF) was positive. If PCR was negative, the diagnosis also could be confirmed if serum or CSF Zika IgM was elevated in the presence of negative dengue serum IgM. If serum IgM for dengue was positive, further testing was needed to demonstrate that CSF IgM was negative, to exclude cross-reactivity.
Over the 5.2-month enrollment period, 40 patients were identified and included in this prospective analysis. These included 29 cases of GBS, seven cases of encephalitis, three cases with transverse myelitis, and one case of chronic inflammatory demyelinating polyneuropathy (CIDP). Median age of the patients was 44 years, and 38% were women. Eighty percent of the GBS/CIDP patients underwent electrodiagnostic studies. Compared to the reference period of 2013-2014, admissions for GBS, encephalitis, and transverse myelitis increased four-fold. Of the 40 patients included in the analysis, 35 (88%) had evidence of acute Zika virus infection. Three of the patients had positive Zika virus PCR and the remainder met diagnostic criteria by IgM testing. Positive testing for Zika infection was seen in 27 of 29 GBS patients, five of seven encephalitis patients, two of three transverse myelitis patients, and the single CIDP case. All patients were tested for HIV and other causes of these syndromes. Of the patients who tested negative for Zika virus, one had GBS following a yellow fever vaccine and two had encephalitis associated with chikungunya infection.
Of the patients who tested positive for Zika virus, 91% reported a viral prodrome, most commonly fever and rash. Median time from prodrome to development of neurologic symptoms was 10 days. Of the 35 patients who tested positive for Zika virus, 26% required admission to the ICU and 14% required mechanical ventilation. Three patients died: one with encephalitis who developed refractory brain edema and herniation, and two with GBS who developed hospital-associated pneumonia.
This is an important study because it collected patients prospectively, allowing for the evaluation of all patients who presented with a neuroinflammatory clinical syndrome. The study demonstrates that GBS is an important neurologic complication of Zika virus infection, which is consistent with all prior studies. Additionally, this study sheds new light on the neurologic complications of Zika virus infection, suggesting that encephalitis and transverse myelitis also may be associated with Zika virus infection. The study was limited by the authors pre-defining the syndromes that they suspected might be associated with Zika virus, possibly leaving out other syndromes that possibly could be associated if tested. However, overall, this study is valuable in that it demonstrates a significant increase in neuroinflammatory syndromes, presumably related to Zika infection, and expands the list of conditions that may be related to Zika infection.