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.
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.
Authors: Marli T Cordeiro; Carlos A A Brito; Lindomar J Pena; Priscila M S Castanha; Laura H V G Gil; Kennya G S Lopes; Rafael Dhalia; Jucille A Meneses; Ana C Ishigami; Luisa M Mello; Liciana X E Alencar; Klarissa M Guarines; Laura C Rodrigues; Ernesto T A Marques Journal: J Infect Dis Date: 2016-10-05 Impact factor: 5.226
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Authors: So-Yon Lim; Christa E Osuna; Katharine Best; Ray Taylor; Elsa Chen; Gyeol Yoon; Jessica L Kublin; Dane Schalk; Nancy Schultz-Darken; Saverio Capuano; David Safronetz; Ma Luo; Steve MacLennan; Amanda Mathis; Yarlagadda S Babu; William P Sheridan; Alan S Perelson; James B Whitney Journal: Sci Transl Med Date: 2020-06-10 Impact factor: 17.956
Authors: Maíra Cardoso Aspahan; Sonja Emily Leonhard; Rodrigo Santiago Gomez; Eder da Silva Rocha; Michelle Ramos da Silva Vilela; Pedro Paulo Martins Alvarenga; Paula Eillanny Silva Marinho; Erna Geessien Kroon; Fidel Meira Journal: Neurol Clin Pract Date: 2019-02
Authors: Kelly R Silva; Blanca E R G Bica; Eduardo S Pimenta; Rodrigo B Serafim; Mirhelen M Abreu; Jorge L S Gonçalves; Larissa de S Santana; Mauro J Cabral-Castro; José M Peralta; Marta G Cavalcanti Journal: Diseases Date: 2018-06-21