Neurologic Complications Associated With the Zika Virus in Brazilian Adults

Abstract

There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults.OBJECTIVE To evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barré syndrome (GBS), meningoencephalitis, or transverse myelitis. DESIGN, SETTING, AND PARTICIPANTSA prospective, observational cohort study was conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (>18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed.INTERVENTIONS Samples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase-polymerase chain reaction and an IgM antibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected. MAIN OUTCOMES AND MEASURESThe detection of neurologic complications secondary to ZIKV infection.RESULTS Forty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transverse myelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transverse myelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, to May 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5). CONCLUSIONS AND RELEVANCEIn this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical.

Zika virus and Guillain–Barré syndrome in Bangladesh

“…First, confirmation of a preceding ZIKV infection in GBS patients is generally complicated by the delay between infection and the first neurological manifestations of GBS as mentioned in previous studies 4, 35. In this study, there was an additional delay between this neurological onset and hospital admission that further reduced the chances of demonstrating the viral genome in serum.…”

“…Up to present, studies describing the role of ZIKV in GBS have focused on outbreak areas and symptomatic ZIKV patients 4, 5, 8, 9, 25, 26, 27. Interestingly, ZIKV infections are symptomatic in only an estimated 20% of cases and ZIKV will probably soon be endemic in most affected areas.…”

“…Major outbreaks of Zika virus (ZIKV), a mosquito‐borne neurotropic flavivirus, have been reported in the island of Yap (2007), French Polynesia (2013–2014), and several Latin‐American countries (2014) 1, 2, 3, 4. During the ZIKV outbreak in French Polynesia, a profound 20‐fold increase in the number of Guillain–Barré syndrome (GBS) was reported 5.…”

“…GBS is an acute polyradiculoneuropathy causing a rapidly progressive limb weakness and is triggered by various types of preceding infection 6. Recently, the association between ZIKV and GBS has also been reported in various Latin‐American countries following outbreaks of ZIKV 4, 7, 8, 9. In Asia, where ZIKV has been endemic for several decades,10, 11, 12 the occurrence of GBS and other neurological complications after ZIKV infection have thus far not been reported.…”

Has the threat of Zika virus outbreaks come to an end?

“…ZIKV has caused meningoencephalitis in people of all ages, including immunedepressed patients 5 . Therefore, it is important to consider that an arbovirus requires special capabilities to infect the CNS.…”