Neurologic Complications Associated With the Zika Virus in Brazilian Adults

Abstract

Importance: 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 participants: A 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 measures: The 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 relevance: In 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.

Figure 1.. Flowchart of Enrollment

CIDP indicates chronic inflammatory demyelinating polyneuropathy; GBS, Guillain-Barré syndrome; and ZIKV, Zika virus.

Figure 2.. Magnetic Resonance Imaging (MRI) Findings in Patients With Zika Virus (ZIKV)–Associated Neurologic Complications

A, Axial T2-weighted MRI scan of the thoracic spine of a patient positive for ZIKV infection with encephalitis and lower motor neuron signs. The white arrowhead indicates signal hyperintensity in the area of the anterior horn cells. B, Axial, postcontrast, fat-suppressed T1-weighted MRI scan of the lumbar spine demonstrates contrast enhancement of the nerve roots and cauda equine in a patient with Guillain-Barré syndrome positive for ZIKV infection (white arrowhead). C, Axial, postcontrast, fat-suppressed T1-weighted MRI scan shows gadolinium enhancement of both facial nerves in a patient with Guillain-Barré syndrome positive for ZIKV infection (white arrowheads).