Zika Virus Now Linked to Autoimmune Neurologic Conditions

April 12, 2016

The latest complications associated with the Zika virus epidemic in Brazil include two different and serious autoimmune neurologic conditions.

A new report documents both acute disseminated encephalomyelitis (ADEM) and Guillain-Barré syndrome in patients with recent Zika virus infection.

The authors saw 151 cases with neurologic manifestations from December 2014 to December 2015 at the Hospital da Restauração, Pernambuco, Brazil.

They report details of six patients seen in the emergency department and the neurology outpatient department of the hospital between December 2014 and June 2015: two with ADEM and four with Guillain-Barré syndrome.

All six patients had experienced fever and rash and some had pruritus, myalgia, arthralgia, and conjunctival hyperemia. Neurologic complications appeared 0 to 15 days later. Blood and cerebrospinal fluid molecular tests for arboviruses were positive only for Zika virus.

MRI showed white matter lesions in two cases and elevated protein concentration with normal cell count in the four cases of Guillain-Barré syndrome. After hospital discharge, five patients had sustained motor dysfunction, one patient had low visual acuity, and another had cognitive decline.

"There is strong evidence that this epidemic has different neurological manifestations than those referred to in the literature," the authors, led by Maria Lucia Brito Ferreira, MD, Restoration Hospital, Recife, Brazil, conclude. "Though our study is small, it may provide evidence that in this case the virus has different effects on the brain than those identified in current studies."

Their findings were released April 10 and will be presented in full at the upcoming American Academy of Neurology (AAN) 2016 Annual Meeting in Vancouver, Canada.

Zika Keeps "Giving New Surprises"

Commenting for Medscape Medical News, infectious disease specialist William Schaffner, MD, Vanderbilt Medical Center, Nashville, Tennessee, pointed out that Guillain-Barré syndrome had been linked to Zika in other parts of the world but, to his knowledge, this is the first report of ADEM associated with the virus.

"I am not aware of ADEM being associated with Zika before," he said. "Zika keeps giving us these new surprises. However, Guillain-Barré syndrome has been seen with Zika in Polynesia, and ADEM is not dissimilar to Guillain-Barré syndrome — you could say it is like a second cousin — so perhaps it is not that surprising."

Dr Schaffner explained that ADEM and Guillain-Barré syndrome are both immunologic neurologic conditions that can be triggered by infectious insults. "They are both quite uncommon, and it is only partially understood how the body creates an aberrant immunological response to infections."

"I would say that although there are only a few cases reported in this study, they are clearly described."

He added: "As this Zika epidemic progresses, we are finding more and more complications that it appears to cause. We are learning that it can invade neurological tissue directly, which is how it causes the microcephaly in fetuses, and it has been associated with visual and hearing defects in newborns, also probably a result of direct infection of neurological tissues. And MRI studies of adults recovering from Zika infection have shown lesions in the brain."

"But these reports of ADEM and Guillain-Barré syndrome suggest a different mechanism — that the virus is triggering an immunological response that is causing these neurological conditions."

Dr Schaffner noted that a large outbreak of Guillain-Barré syndrome has previously been reported in French Polynesia after an outbreak of Zika there. "We believe this is the same virus we are now seeing in the western hemisphere, which was probably introduced in late 2014 and has exploded."

"Tip of the Iceberg"

He says more cases of these neurologic illnesses are bound to be reported. "This report is likely to be the tip of the iceberg. I think physicians who come across new suspected cases of Guillain-Barré syndrome or ADEM should ask patents if they have been to Zika countries. That may help with diagnosing the conditions."

James Sejvar, MD, from the Centers for Disease Control and Prevention, and a member of the AAN, is quoted in the AAN statement as saying: "At present, it does not seem that ADEM cases are occurring at a similarly high incidence as Guillain-Barré syndrome, but these findings from Brazil suggest that clinicians should be vigilant for the possible occurrence of ADEM and other immune-mediated illnesses of the central nervous system."

He added: "The remaining question is 'why' — why does Zika virus appear to have this strong association with GBS [Guillain-Barré syndrome] and potentially other immune/inflammatory diseases of the nervous system? Hopefully, ongoing investigations of Zika virus and immune-mediated neurologic disease will shed additional light on this important question."

Dr Ferreira has received personal compensation for activities with Novartis, Sanofi, Baxter, and Teva for serving on the advisory board and as a speaker.

American Academy of Neurology (AAN) 2016 Annual Meeting. Emerging Science 004. To be presented April 19, 2016.

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