Clinical Features of Acute Flaccid Myelitis Temporally Associated with an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August–December 2015

Abstract

Backgroud

Acute flaccid myelitis (AFM) is an acute flaccid paralysis (AFP) syndrome with spinal motor neuron involvement of unknown etiology. We investigated the characteristics and prognostic factors of AFM clusters coincident with an enterovirus D68 (EV-D68) outbreak in Japan during autumn 2015.

Methods

An AFM case series study was conducted following a nationwide survey from August to December 2015. Radiographic and neurophysiologic data were subjected to centralized review, and virology studies were conducted for available specimens.

Results

Fifty-nine AFM cases (58 definite, one probable) were identified, including 55 children and four adults (median age, 4.4 years). The AFM epidemic curve showed strong temporal correlation with EV-D68 detection from pathogen surveillance, but not with other pathogens. EV-D68 was detected in nine patients: five in nasopharyngeal, two in stool, one in cerebrospinal fluid (adult case), and one in tracheal aspiration, nasopharyngeal, and serum samples (a pediatric case with preceding steroid usage). Cases exhibited heterogeneous paralysis patterns from one- to four-limb involvement, but all definite cases had longitudinal spinal gray matter lesions on MRI (median 20 spinal segments). Cerebrospinal fluid pleocytosis was observed in 50/59 cases (85%), and 8/29 (28%) were positive for anti-ganglioside antibodies, as frequently observed in Guillain-Barré syndrome. Fifty-two patients showed variable residual weakness at follow-up. Good prognostic factors included a pretreatment manual muscle strength test unit score >3, normal F-wave persistence, and EV-D68-negative status.

Conclusions

EV-D68 may be one of the causative agents for AFM, while host susceptibility factors such as immune response could contribute to AFM development.