From the Journals

Further evidence links Zika, Guillain-Barré syndrome

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Study is promising, but more work needs to be done

Dr. Parra and her colleagues report in the Journal the results of a prospective study of 68 Colombian patients who had a syndrome consistent with the Guillain-Barré syndrome, 66 of whom had previously had symptoms of Zika virus (ZIKV) infection. Major strengths of this study include the documentation of a temporal relationship between the Guillain-Barré syndrome and ZIKV infection (marked by a substantial increase in the incidence of the Guillain-Barré syndrome after the introduction of ZIKV, from 20 to 90 cases per month throughout Colombia), the criteria applied for the diagnosis of the Guillain-Barré syndrome, and the molecular and serologic flavivirus data from analyses of serum, cerebrospinal fluid, and urine.

The difficulties in diagnosing ZIKV infection are borne out in this study, as only 17 patients had definitive laboratory evidence of recent ZIKV infection. Of these 17 patients, only 14 had electrophysiologic data consistent with the Guillain-Barré syndrome and therefore could have met Brighton level 1 diagnostic criteria for the syndrome. Among the 25 ZIKV PCR–negative patients, dengue virus (DENV) IgG antibodies were present in the cerebrospinal fluid of 12 patients and in the serum of 10 patients, and serum DENV IgM test results were positive in 1. These data raise the possibility of primary DENV infection and false-positive ZIKV serologic test results from cross reactivity.

Overall, the study by Dr. Parra and her colleagues supports the association between ZIKV and the Guillain-Barré syndrome, although confirmation in another cohort would strengthen this assertion. Although high rates of seropositivity may prove protective against further waves of ZIKV-related Guillain-Barré syndrome in Central and South America, the ZIKV pandemic is just beginning in North America and Africa, and an increase in the incidence of the Guillain-Barré syndrome may follow.

Jennifer A. Frontera, MD, is with the Cerebrovascular Center at the Cleveland Clinic in Cleveland. Ivan R.F. da Silva. MD, is with the Federal Fluminense University in Niterói, Brazil. These comments were adapted from their editorial accompanying the study ( N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMe1611840 ).


Evidence of Zika virus found in Colombian patients with Guillain-Barré syndrome supports the theory that Zika virus infection and Guillain-Barré syndrome are related and could occur parainfectiously, according to a study published in the New England Journal of Medicine.

“Our study provides virologic evidence of [Zika virus] infection in patients with Guillain-Barré syndrome,” wrote Beatriz Parra, PhD, of the Hospital Universitario del Valle in Valle del Cauca, Colombia, and her coauthors (N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMoa1605564).

The study looked at 68 patients with Guillain-Barré syndrome, all of whom received their diagnoses at one of six university-based health care centers across Colombia between January and March 2016. Median age was 47 years, 56% were male and 90% of mixed race. All 68 patients were evaluated clinically for Guillain-Barré syndrome and underwent neurologic evaluation as well. Of the 68 subjects, 42 also underwent laboratory testing to find Zika virus RNA in either blood, cerebrospinal fluid, or urine, via reverse-transcriptase polymerase chain reaction (RT-PCR) testing.

Results indicated that 66 (97%) of subjects had symptoms consistent with a Zika virus infection prior to the onset of Guillain-Barré syndrome. The median number of days between onset of Zika-like symptoms and the onset of Guillain-Barré syndrome was found to be 7 days (interquartile range, 3-10 days). Seventeen (40%) of the 42 patients who underwent laboratory testing tested positive for Zika virus RNA in their sample, with 16 of those 17 positive tests coming from urine samples. Additionally, 18 of the 42 laboratory-tested subjects had “clinical and immunologic findings [that] supported” a Zika virus infection.

“The onset of the Guillain-Barré syndrome can parallel the onset of systemic manifestations of [Zika virus] infection, indicating a so-called parainfectious onset, which suggests that factors different from the known postinfectious mechanisms may be present in [Zika virus]–related Guillain-Barré syndrome,” the authors explained, adding that 20 (48%) of the 42 laboratory-tested subjects had a parainfectious onset.

“RT-PCR testing of urine is a valuable diagnostic tool for the identification of [Zika virus] infection in patients with Guillain-Barré syndrome,” Dr. Parra and her coauthors concluded.

The study was funded by the Bart McLean Fund for Neuroimmunology Research, Johns Hopkins Project Restore, and the Universidad del Valle. Dr. Parra reported no relevant financial disclosures.

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