Zika Linked to Rising Tide of Serious Neurologic Complications in Adults

Nancy A. Melville

August 15, 2017

A rising tide of serious neurologic complications among adults in Brazil has been linked to the spread of the Zika virus, new research shows.

"Our study is the first prospective study assessing the occurrence of neurological complications in adults secondary to Zika virus infection, with all previous data based solely on case series and case reports," senior author, Osvaldo Jose Moreira do Nascimento, MD, PhD, from the Neurology Department at Universidade Federal Fluminense, Copacabana, Rio de Janeiro, Brazil, told Medscape Medical News.

"We observed an increase in the admissions of patients with inflammatory complications, such as Guillain-Barré syndrome (GBS), myelitis and encephalitis."

The study was published online August 14 in JAMA Neurology.

ICU Admissions, Disability, Mortality

Zika virus gained notoriety for causing congenital microcephaly in infants born to infected mothers. GBS was the first major neurologic syndrome linked to Zika infection that was not associated with pregnancy. Regions of French Polynesia and the Americas have reported up to a 40-fold increase in GBS associated with the spread of the Zika virus, compared with pre–Zika virus time frames.

The current prospective study included 40 patients at a tertiary referral center for neurologic disease in Rio de Janeiro, Brazil, who had been admitted to the hospital between December 2015 and May 2016 with new-onset acute parainfectious or neuroinflammatory disease.

Of the 40 patients, 15 were women and 25 were men. The median age was 44 years. Twenty-nine (73%) patients had GBS, 7 (18%) had encephalitis, 3 (8%) had transverse myelitis, and 1 (3%) had newly diagnosed chronic inflammatory demyelinating polyneuropathy.

Of these individuals, 35 (88%) showed molecular and/or serologic evidence of recent Zika virus infection in serum or cerebrospinal fluid. This included 27 of the 29 with GBS, 5 of the 7 with encephalitis, 2 with transverse myelitis, and the 1 with chronic inflammatory demyelinating polyneuropathy.

Nine patients required admission to the intensive care unit and 5 required mechanical ventilation. Outcomes at 3 months showed that 2 patients (6%) who were positive for Zika virus died: 1 with GBS and 1 with encephalitis. In addition, 18 patients had chronic pain. Overall, survivors had a median modified Rankin Scale score of 2 (range, 0 to 5).

These findings are consistent with the previous reports of neurologic syndromes associated with Zika virus in other populations, the authors note.

"The rates of admissions to the intensive care unit, disability at 3 months, and mortality did not differ substantially in our cohort compared with other published cohorts of [Zika virus]-associated GBS from Colombia and French Polynesia.

"In addition, our outcomes were similar to those observed in a large cohort of patients from Europe with GBS secondary to other causes. However, our cohort had lower rates of mechanical ventilation," they write.

Compared with a seasonally similar time frame before the first documented Zika virus case, hospital admissions for GBS in the current study time frame of 2015 to 2016 showed increases from a mean of 1.0 per month to 5.6 per month. Encephalitis admissions increased from 0.4 per month to 1.4 per month and admissions for transverse myelitis remained steady at 0.6 per month.

Dr Nascimento noted that the study did not identify factors associated with development of neurologic complications with Zika virus infection.

"Our study was not powered nor designed to compare patients with [Zika virus] who developed neurological complications in comparison those who did not," he said.

"What we might say is that neurological complications were observed in a population with diverse social and ethnic backgrounds, with grossly similar prevalence of chronic diseases as expected in a Brazilian cohort, involving patients with ages from young adulthood to elderly citizens," he added.

Importantly, the study used concomitant testing of Zika virus in patient serum as well as cerebral spinal fluid (CSF) samples and was the first to simultaneously test for CSF, Zika virus, and dengue IgM antibodies in order to exclude the confounder of cross-reactivity from flavivirus, which is highly common in Central and South America.

"We believe that our method of matching CSF and blood serologic findings offers a substantial aid to minimize cross-reactivity in countries with a high prevalence of other concurrent flavivirosis," the authors note.

Although there were some differences in the manifestation of GBS in Zika virus–infected patients compared with GBS secondary to more traditional causes, outcomes were roughly similar. All patients with GBS received the standard treatment of intravenous immunoglobulin, Dr Nascimento said.

"The only situation in which we observed a more protracted recovery involved patients with GBS and associated encephalitis," he said.

Currently, no known preventive actions can be taken to avoid neurologic injuries. The investigators hope the findings will advance the understanding of the complications, Dr Nascimento noted.

"We believe our study can help educate providers with respect to suspecting these complications early on and make an accurate diagnosis."

Important Contribution

Kenneth L. Tyler, MD, coauthor of an accompanying editorial, said the study adds to the growing understanding of GBS in Zika virus–infected adults, as well as the isolated case reports of other effects, such as encephalitis and myelitis.  

"This study extends this by showing that during epidemics Zika can be responsible for not only many of the GBS cases but also, importantly, cases of myelitis and encephalitis — confirming and extending the case reports," he told Medscape Medical News.

He added that the many unknowns about the link to neurologic disease underscore the need for Zika prevention.

"In some studies of GBS the risk is increased in older individuals," said Dr Tyler, Department of Neurology, University of Colorado School of Medicine, Aurora. His coauthor, MD, Karen Roos, is from the Department of Neurology, Indiana

University School of Medicine, Indianapolis.

"We don't currently have a good antiviral for Zika of proven human clinical efficacy, so avoiding infection through mosquito control at both the personal and larger-scale level is important. Several vaccines are moving through human safety and efficacy trials and may be important in the future if found to be safe and immunogenicity and effective," he added.

The study was funded by an award from the Cleveland Clinic Foundation. Coauthor Ana Maria Bispo de Fillipis reported receiving grants from Conselho Nacional de Desenvolvimento e Pesquisa and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. The other study authors and the editorialists have disclosed no relevant financial relationships.

JAMA Neurol. Published online August 14, 2017. Abstract, Editorial

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