New Evidence Substantiates Guillain-Barré Syndrome–Zika Virus Link

Researchers have now identified virologic evidence of Zika virus in patients with Guillain-Barré syndrome (GBS), showing that the onset of the neurologic disorder can parallel the onset of systemic manifestations of the mosquito-borne infection.

Earlier studies have linked GBS and other neurologic issues with Zika virus; however, this research is arguably the first to substantiate the link—beyond epidemiologic evidence—in multiple patients. The findings were published in the October 5 issue of The New England Journal of Medicine.

The authors of the study, from various institutions in Colombia as well as the Johns Hopkins School of Medicine in Baltimore, identified 68 patients from 6 university-based centers in the South American country who had been diagnosed with GBS during a Zika outbreak. The patients were evaluated prospectively as part of the Neuroviruses Emerging in the Americas Study (NEAS) and each underwent clinical and neurologic evaluation by internal medicine and neurology specialists. Clinicians performed nerve-conduction studies and electromyography and obtained samples of blood and cerebrospinal fluid (CSF) for use in virologic testing for Zika as well as confirmation of GBS diagnosis. GBS diagnosis was based on the Brighton Collaboration GBS Working Group criteria. In patients with a diagnosis of the GBS level 1, 2, or 3, based on the Brighton criteria, Zika diagnosis was defined as definite, probable, or suspected, with definite cases being those confirmed via RT-PCR assay and probable cases being those with positive ELISA results.

“To characterize the temporal profile of the disorder, the onset of suspected [Zika virus] infection was defined as the day of onset of systemic symptoms outlined in the case definition,” the authors wrote. “The onset of neurologic symptoms was defined as the first day of onset of limb weakness, sensory symptoms, facial paralysis, or other neurologic symptoms.”

According to the authors, from October 2015 through March 2016, there were 2,603 laboratory-confirmed Zika cases in Colombia and more than 58,790 suspected cases. Additionally, 401 patients with a history of Zika had been diagnosed with a neurologic syndrome, and 270 these involved GBS. The authors noted that, based on unpublished data, an average of 250 cases of GBS were diagnosed annually between 2009 and 2015.

Of the 68 patients enrolled in the study, 56 patients had Brighton level 1 or 2 GBS, while 4 had Miller Fisher syndrome, and 2 had other GBS variants (ie, bilateral facial palsy with areflexia and a pure sensory syndrome). The median age of enrolled patients was 47 years, and 38 were male. In all, 66 had symptoms of Zika in the 4 weeks preceding the onset of their neurologic symptoms; the other 2 were residents of an area affected by the Zika outbreak.

Median duration of Zika symptoms was 4 days, and median time between the onset of the infection and the onset of GBS was 7 days. The authors noted that cranial neuropathies were present in 43 patients, with bilateral facial palsy being the most common (50%). The median modified Rankin score (for disability; 0-6) at nadir was 4, and 36 patients were diagnosed with the acute inflammatory demyelinating polyneuropathy (AIDP) subtype of GBS. Of the 68 GBS patients, 42 underwent laboratory testing for Zika. Only 2 of the patients did not have any symptoms of Zika prior to developing neurologic symptoms, and 2 patients had simultaneous onset of Zika and neurologic symptoms. In all, 17 patients tested positive for Zika by RT-PCR, with most of the positive results were in urine samples; 3 patients had positive results in CSF, and only 1 had a positive blood test. In addition, 32 of 37 patients who underwent ELISA testing had results indicating the presence of immune responses to Zika (ie, IgG, IgM, or both.)

“The identification of the Zika genome by RT-PCR in biologic samples from 17 patients with GBS, together with the presence of immune responses to flaviviruses in the CSF in most of the patients tested, supports the involvement of [Zika] in these cases,” the authors wrote. “These observations suggest that in cases of [GBS] associated with [Zika], the [GBS] may follow the pattern of a parainfectious disorder rather than the classic postinfectious profile. Another important observation in our study is the finding that in patients with [GBS] and definite [Zika] infection, there is a prolonged period of viruria, which persists for days after the viral syndrome is over. Although the frequency of detection of Zika genome in CSF and serum was low, the higher frequency of detection of [virus RNA] in urine makes this biologic sample one that can be considered potentially useful for the diagnosis of [Zika].”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.