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Identification of Enterovirus at Presentation Predicts Outcomes in Acute Flaccid Myelitis A Canadian Nationwide Study in Canada

Background: Acute flaccid myelitis (AFM) is characterized by rapid onset of limb weakness with spinal cord grey matter abnormalities on magnetic resonance imaging (MRI). It is unclear whether detection of enterovirus (EV) in respiratory or other specimens can help predict prognosis in children with AFM. 
 
Methods: In this nationwide longitudinal study, we evaluated the significance of peripheral detection of EV in predicting outcomes in a cohort of Canadian children presenting with AFM in 2014 and 2018. Clinical data, laboratory findings, treatment, and neuroimaging were collected (follow up period up to five years). We assessed neurologic function and motor outcomes using Kurtzke’s Expanded Disability Status Scale (EDSS) and a “weakest limb score” (WLS). 
 
Findings: 58 children with AFM (median 5⋅1 years [IQR 3⋅8-8⋅3]) were identified across five provinces. Twenty-two (39%) children had detectable EV in at least one specimen: EV-D68 in 14 (64%), EV-A71 in two (9%), coxsackievirus, and untyped EV in eight (36%). Children with EV detected were more likely to have had quadriparesis (55% vs. 12%, p=0⋅005), bulbar weakness (50% vs 6%, p=0⋅004), bowel/bladder dysfunction (59% vs 24%, p=0⋅033), cardiovascular instability (36% vs 6%, p=0⋅032), and were more likely to require intensive care unit admission (59% vs. 15%, p 0⋅005). On MRI, most children with EV positivity showed brainstem pontine lesions (59%), while other MRI parameters did not correlate with EV status. EDSS of EV+ and EV- groups was significantly different at baseline (median 8⋅5 [interquartile range, IQR 4-9⋅5] vs. 4⋅8 [IQR 3⋅4-7⋅1], p=0⋅012) and 12 months (median 3 [IQR 3-7] vs. 3 [IQR 2-3], p=0⋅036). Kaplan-Meier survival analysis of a subgroup of patients showed significantly poorer motor recovery among children with detected EV than those tested negative (p=0⋅032). 
 
Interpretation: Detection of EV in specimens from non-sterile sites at presentation correlated with more severe acute motor weakness, worse overall outcomes and poorer trajectory for motor recovery. 
 
Funding Statement: None. 
 
Declaration of Interests: EAY reports grants from Canadian Network of MS Clinics during the conduct of the study; grants from Biogen, grants from NMSS, grants from CMSC, grants from 18 MSSC/MS Foundation, grants from OIRM, grants from SCN, grants from SickKids Foundation, personal fees from ACI, personal fees from US FDA, grants from CBMH, grants from TEVA, grants from Guthy Jackson Foundation, personal fees from Juno, outside the submitted work. All other authors have no conflict of interest to disclose. 
 
Ethics Approval Statement: This study was approved by the research ethics board/committee of all above-listed participating institutions. Informed consents were obtained according to individual institutional requirements.