By Joseph E. Safdieh, MD

Vice Chair and Associate Professor, Weill Cornell Medical College

Dr. Safdieh reports no financial relationships relevant to this field of study.

SYNOPSIS: Guillain-Barré syndrome is a defined complication of Zika virus infection and presents in a typical manner, similar to other post-viral GBS syndromes.

SOURCE: Dirlikov E, Major CG, Mayshack M, et al. Guillain-Barre’ syndrome during ongoing Zika virus transmission – Puerto Rico, January 1 – July 31, 2016. MMWR Morb Mortal Wkly Rep 2016;65:910-914.

Zika virus is a flavivirus that recently has garnered worldwide attention, as it is associated with microcephaly in children born to mothers infected during pregnancy. Zika virus is transmitted by a mosquito vector, and is unique in that it can be transmitted sexually from an infected human to an uninfected partner. Zika virus outbreaks have occurred in Central and South America as well as the Caribbean, and recently, cases have been transmitted from mosquitoes in parts of Florida. In addition to its well-described effects on a developing fetus, there have been indications that Zika virus is associated with the subsequent development of post-infectious Guillain-Barré syndrome (GBS).

To study the association between Zika and GBS, the Department of Health in Puerto Rico, with the assistance of the CDC, set up a registry of all cases of GBS to determine the clinical characteristics, as well as recent Zika exposure. Dirlikov et al reviewed the cases of GBS between January and July 2016, when Zika activity in Puerto Rico was high. Physicians were requested to submit all GBS cases to a central registry along with samples of serum, urine, saliva, and cerebrospinal fluid. All specimens were tested with polymerase chain reaction (PCR) as well as immunoglobulin M (IgM) for Zika, Dengue, and Chikungunya. Zika virus infection was confirmed if the PCR was positive and was presumed if the IgM was positive, and flaviviral infection was suspected if both Zika and dengue IgM were positive, as they often cross-react.

Over the six-month period, 56 cases of GBS were reported to the registry. Thirty-four of these patients had suspected or confirmed Zika or flavivirus infection, representing 61% of the GBS cases. Zika was confirmed by PCR in 10 of these cases. Sixteen of these cases had presumptive Zika infection (negative PCR, positive Zika IgM) and eight had presumptive flavivirus infection (positive Zika and Dengue IgM). Twenty patients in the GBS cohort had no evidence of Zika infection.

Of the 34 cases of GBS associated with confirmed or presumptive Zika infection, the median age at diagnosis was 55 years. Fifty-nine percent of the patients were women. Ninety-four percent of the patients recalled an antecedent illness within two months of GBS diagnosis, most commonly rash, fever, or diarrhea. The median time from antecedent illness to GBS diagnosis was only five days. Patients presented in a typical fashion with limb weakness, facial weakness, areflexia, numbness, and dysphagia. All patients demonstrated cerebrospinal fluid cytoalbuminologic dissociation. Only five patients underwent electrophysiologic studies, all of which demonstrated the demyelinating subtype of GBS. All patients were hospitalized and treated with IVIG. Sixty-two percent of patients required ICU care and 35% required mechanical ventilation. Forty-four percent of patients were discharged home, and 38% were discharged to a rehabilitation facility. At the time of publication, 18% remained hospitalized. One patient died of sepsis.

COMMENTARY

GBS is often triggered by a viral infection, and it is not surprising that the immune activation caused by viral infection of a previously immune-naïve population would trigger molecular mimicry in some patients leading to autoimmune demyelination. Given the likely continued spread of Zika virus into the United States, it certainly would not be surprising if there were an uptick in GBS cases. The fact that 61% of cases of GBS over a six-month period in Puerto Rico were attributed to confirmed or presumed Zika infection is quite impressive and suggests that the association between Zika and GBS is strong, although the absolute number of GBS cases is low as compared to the presumed number of Zika-infected patients.

There does not appear to be much difference between Zika-associated GBS and the GBS we typically see in routine clinical practice, although longer-term follow-up would certainly be needed to confirm this. Despite earlier reports of axonal-variant GBS being associated with Zika, the current cases studied were demonstrated to be the more typical, and more treatment-responsive, demyelinating form. Treatment of Zika-associated GBS is the same as GBS due to any other cause. Neurologists should consider Zika testing in patients with GBS, especially in areas of the country where Zika is prevalent, or if patients have traveled to Zika-infested areas before developing illness.