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Background Several enteroviruses (EVs), including EV-A71 and EV-D68, have been associated with acute flaccid myelitis (AFM). Clinical features distinguishing AFM presentations associated with specific EV types are not well described. Methods EV-associated AFM was defined as any child presenting to Children's Hospital Colorado in 2013–2018 who met the Council of State and Territorial Epidemiologists definition for confirmed AFM (flaccid limb weakness with longitudinal gray-matter-predominant spinal cord lesion on MRI) and had EV-A71 or EV-D68 identified in any biologic specimen (cerebrospinal fluid [CSF], nasopharyngeal [NP], oropharyngeal [OP], rectal) by VP1-specific RT-PCR and sequencing. Summative limb strength scores (SLSS) were calculated by adding Medical Research Council strength scores (1–5) for all limbs. Results Ten cases of EV-A71-associated AFM were identified, all from 2018; 8 cases of EV-D68-associated AFM were identified from 2013 (1), 2014 (4), 2016 (1), and 2018 (2) [Table 1]. Viral detection rates were higher in rectal and OP swabs in EV-A71 cases and NP specimens in EV-D68 cases. Virus was not detected in CSF of EV-D68 cases and in 1 EV-A71 case. EV-A71 cases were younger (median 19 vs. 100 months) and had neurologic onset earlier after prodromal symptom onset (median 1 vs. 5.5 days) than EV-D68 cases. Hand, foot, and/or mouth lesions distinguished EV-A71 cases, whereas respiratory symptoms were uniformly noted in EV-D68 cases. Associated neurologic findings more commonly associated with EV-A71 cases than EV-D68 cases included irritability, myoclonus, and ataxia. Weakness was more generalized with EV-A71 and more asymmetric with EV-D68, though patterns of brainstem and spinal cord involvement on MRI were similar. Compared with EV-D68, EV-A71 cases had milder weakness at onset and improved strength at 1- to 2-month follow-up (Figure 1), shorter length of stay (median 5.5 vs. 32 days) and a greater rate of full neurologic recovery (90% vs. 13%). Conclusion EV-D68 and EV-A71 are both associated with AFM with similar MRI findings, but cases can be distinguished by associated prodromal symptoms, neurologic findings, and outcomes. Timely collection and testing of nonsterile site specimens, particularly NP for EV-D68 and OP and rectal for EV-A71, are key to case identification. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]