The evidence of ZIKV infection documented by RT-PCR among patients with the Guillain-Barré syndrome during the outbreak of ZIKV infection in Colombia lends support to the role of the infection in the development of the Guillain-Barré syndrome. (Funded by the Bart McLean Fund for Neuroimmunology Research and others.).

The 2015-2016 epidemic of Zika virus (ZIKV) in the Americas and the Caribbean was associated with an unprecedented burden of neurological disease among adults. Clinically, Guillain-Barre syndrome (GBS) predominated among regions affected by the ZIKV epidemic, but the spectrum of neurological disease in the adults appears broader as cases of encephalopathy, encephalitis, meningitis, myelitis, and seizures have also been reported. A para-infectious temporal profile of ZIKV-associated GBS (ZIKV-GBS) has been described in clinical studies, which may suggest a direct viral neuropathic effect. However, ZIKV neuropathogenesis has not yet been fully understood. Mechanisms for ZIKV-GBS and other neurological syndromes have been hypothesized, such as adaptive viral genetic changes, immunological interactions with other circulating flaviviruses, and host and factors. This review summarizes the current evidence on ZIKV-associated neurological complications in the adults.

IMPORTANCE Acute flaccid myelitis (AFM) is an emerging poliolike illness of children whose clinical spectrum and associated pathogens are only partially described. The case definition is intentionally encompassing for epidemiologic surveillance to capture all potential AFM cases. Defining a restrictive, homogenous subpopulation may aid our understanding of this emerging disease. OBJECTIVE To evaluate the extent to which the US Centers for Disease Control and Prevention (CDC) case definition of AFM incorporates possible alternative diagnoses and to assess the plausibility of a case definition that enriches the biological homogeneity of AFM for inclusion in research studies. DESIGN, SETTING, AND PARTICIPANTS Retrospective case analysis of children younger than 18 years diagnosed as having AFM between 2012 and 2016 using the CDC case definition. Group 1 included patients recruited from the United States and Canada based on the CDC case definition of AFM. Group 2 included patients referred to the Johns Hopkins Transverse Myelitis Center for evaluation of suspected AFM. Patients' records and imaging data were critically reviewed by 3 neurologists to identify those cases with definable alternative diagnoses, and the remaining patients were categorized as having restrictively defined AFM (rAFM). Clinical characteristics were compared between patients with rAFM (cases) and those with alternative diagnoses, and a case description distinguishing these AFM groups was identified. Interrater reliability of this description was confirmed for a subset of cases by a fourth neurologist. Data were analyzed between May 2017 and November 2018. MAIN OUTCOMES AND MEASURES Proportion of patients with possible alternative diagnosis. RESULTS Of the 45 patients who met the CDC AFM case definition and were included, the mean age was 6.1 years; 27 were boys (60%); and 37 were white (82%), 3 were Asian (7%), 1 was Hispanic (2%), and 4 were mixed race/ethnicity (9%). Of the included patients, 34 were classified as having rAFM, and 11 had alternate diagnoses (including transverse myelitis, other demyelinating syndromes, spinal cord stroke, Guillain-Barre syndrome, Chiari I myelopathy, and meningitis). Factors differing between groups were primarily asymmetry of weakness, lower motor neuron signs, preceding viral syndrome, symptoms evolving over hours to days, absence of sensory deficits, and magnetic resonance imaging findings. A case description was able to reliably define the rAFM group. CONCLUSIONS AND RELEVANCE We present an approach for defining a homogeneous research population that may more accurately reflect the pathogenesis of the prototypical poliomyelitis-like subgroup of AFM. The definition of rAFM forms a blueprint for inclusion criteria in future research efforts, but more work is required for refinement and external validation.