Guillain-Barré syndrome related to Zika virus infection: A systematic review and meta-analysis of the clinical and electrophysiological phenotype

BACKGROUND: The Zika virus (ZIKV) has been associated with Guillain-Barré syndrome (GBS) in epidemiological studies. Whether ZIKV-associated GBS is related to a specific clinical or electrophysiological phenotype has not been established. To this end, we performed a systematic review and meta-analysis of all published studies on ZIKV-related GBS. METHODS: We searched Pubmed, EMBASE and LILACS, and included all papers, reports or bulletins with full text in English, Spanish or Portuguese, reporting original data of patients with GBS and a suspected, probable or confirmed recent ZIKV infection. Data were extracted according to a predefined protocol, and pooled proportions were calculated. RESULTS: Thirty-five studies were included (13 single case reports and 22 case series, case-control or cohort studies), reporting on a total of 601 GBS patients with a suspected, probable or confirmed ZIKV infection. Data from 21 studies and 587 cases were available to be summarized. ZIKV infection was confirmed in 21%, probable in 22% and suspected in 57% of cases. ZIKV PCR was positive in 30% (95%CI 15–47) of tested patients. The most common clinical features were: limb weakness 97% (95%CI 93–99), diminished/absent reflexes 96% (95%CI 88–100), sensory symptoms 82% (95%CI 76–88), and facial palsy 51% (95%CI 44–58). Median time between infectious and neurological symptoms was 5–12 days. Most cases had a demyelinating electrophysiological subtype and half of cases were admitted to the Intensive Care Unit (ICU). Heterogeneity between studies was moderate to substantial for most variables. CONCLUSIONS: The clinical phenotype of GBS associated with ZIKV infection reported in literature is generally a sensorimotor demyelinating GBS with frequent facial palsy and a severe disease course often necessitating ICU admittance. Time between infectious and neurological symptoms and negative PCR in most cases suggests a post-infectious disease mechanism. Heterogeneity between studies was considerable and results may be subject to reporting bias. This study was registered on the international Prospective Register of Systematic Reviews (CRD42018081959).