Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada

Abstract

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.

Co-circulation of multiple enterovirus D68 subclades, including a novel B3 cluster, across Europe in a season of expected low prevalence, 2019/20

“…Following its first identification in 1962, only 699 cases of EV-D68 were reported in scientific literature before 2014 [14]. From 2014 onwards, the epidemiology appears to have changed, and EV-D68 has increasingly been associated with outbreaks of respiratory infections and a concurrent upsurge of AFM [15,16] with poor long-term prognosis [17,18]. We identified 15 sequences, collected from five countries, which formed a distinct cluster within subclade B3 not previously described in Europe, illustrating the rapid evolution and spread of EV-D68.…”

A ten-year retrospective evaluation of acute flaccid myelitis at 5 pediatric centers in the United States, 2005–2014

“…The occurrence of monoplegia/monoparesis (period 1: upper extremity in 2 patients, lower extremity in 1 patient; period 2: upper extremity in 5 patients) is more characteristic of focal CNS involvement, such as that seen with neurotropic infectious pathogens rather than a post-infectious immune-mediated process. Monoplegia has been reported in some AFM cases from most case series covering 2014 and later, most commonly an upper extremity, reflecting the common cervical cord involvement [17,18,[22][23][24][25][26]. The CSF WBC counts were low in many period 1 cases, which may suggest differences in pathogenesis between period 1 and period 2 cases.…”

“…However, among the subset of 74 cases from 2018 with CSF specimens tested at CDC, a pathogen was identified in only 2 cases (EV-D68 and EV-A71 in one CSF specimen each) [20,21]. Non-poliovirus AFM cases have also been reported from several other countries in the recent past [22][23][24][25][26]. The clinical and radiological phenotype termed AFM can be caused by pathogens other than polioviruses, including other enteroviruses (EV-A71) and certain flaviviruses (West Nile virus) [27][28][29].…”

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

“…EV-D68 is the most consistent enterovirus linked with AFM (Kreuter et al, 2011), accounting for up to 50% of all confirmed AFM cases (Lopez et al, 2019), but other enteroviruses such as EV-A71 (Chumakov et al, 1979;Lopez et al, 2019;Lee et al, 2014), CVs (Cho et al, 2017;Lopez et al, 2019), EV-D70 (Bharucha et al, 1972), EV-B93 and EV-D94 (Junttila et al, 2007), echovirus 33 (Grimwood et al, 2003) and echovirus 11 (Moline et al, 2018;Lopez et al, 2019) have also been identified but at a much lower frequency. Although AFM is rare, affecting more than 500 confirmed cases worldwide since 2012 , the prognosis is poor with less than 20% of children fully regaining neurological function within 6 months (Sejvar et al, 2016;Yea et al, 2017;Helfferich et al, 2019). No treatment strategy currently exists for AFM patients but physical rehabilitation which, when implemented during the acute phase of the illness, slightly helps improve long-term neurological outcomes (Van Haren et al, 2015).…”