By Dean L. Winslow, MD, FACP, FIDSA
Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine
Dr. Winslow reports no financial relationships relevant to this field of study.
SYNOPSIS: During the late summer and fall of 2014, cases of acute flaccid myelitis were reported in pediatric patients in the United States. Of 120 cases of acute flaccid myelitis reported, 47% had enterovirus D68 isolated from respiratory secretions when virus isolation was attempted seven days or less after onset of respiratory symptoms.
SOURCE: Sejvar JJ, Lopez AS, Cortese MM, et al. Acute flaccid myelitis in the United States, August-December 2014: Results of a nationwide surveillance. Clin Infect Dis 2016;63:737-745.
Using normal reporting channels (mostly through state and territorial public health laboratories), cases of acute flaccid myelitis (AFM) were reported to the Centers for Disease Control and Prevention (CDC) using a standardized case report form. Cases were defined as occurring in a patient 21 years of age or younger, acute onset of limb weakness from Aug. 1 – Dec. 31, 2014, and spinal magnetic resonance imaging (MRI) showing lesions largely restricted to gray matter.
During this time period, 120 cases were reported from 34 states, median age was 7.1 years, and 59% were male. Eighty-one percent of cases experienced a respiratory illness before the onset of limb weakness. Thirty-four percent of patients had upper extremity involvement only, 23% had lower extremity involvement only, and 25% had involvement of all four extremities. Cranial nerve signs were present in 28%. Fifty-two percent of patients required admission to the ICU and 20% required mechanical ventilation. At a median follow-up time point of 4.2 months following acute illness, 14% of patients were still completely dependent on caretakers, 68% had some degree of functional impairment, and only 18% were fully functional.
Almost all patients had documented MRI abnormalities and were most prominent in the cervical cord (103/118, 80%). Most cases had more than one spinal segment involved. All but one patient was hospitalized, and there were no deaths. Cerebrospinal fluid (CSF) pleocytosis was common, with median CSF white blood cell count of 44 cells/uL with lymphocyte predominance. CSF protein and glucose levels generally were normal. Only one CSF specimen tested positive for enterovirus D68 (EV-D68) by rRT-PCR (and was also positive for Epstein-Barr virus), but this likely was the result of a traumatic tap contaminated by blood.
Fifty-six patients had respiratory specimens submitted to CDC for PCR analysis. Eleven (20%) were positive for EV-D68. Eight of seventeen (47%) respiratory specimens collected seven days or less from respiratory/febrile illness onset were positive for EV-D68. None of 35 sera tested for IgM antibodies to known neurotrophic arboviruses were positive.
Eighty-one percent of cases experienced limb weakness onset between Aug. 1 and Oct. 31, 2014. This time period coincided with peak pediatric ED visits that year for dyspnea and positive test results at CDC for EV-D68.
COMMENTARY
In the late summer/early fall of 2014, pediatricians became aware of a sharp spike in cases of non-polio AFM. These cases were tightly clustered in time. Anecdotally, experienced clinicians from many locations expressed that the number of cases of AFM they were seeing was unprecedented. Since the eradication of wild-type polio from the Western hemisphere 25 years ago, most cases of acute flaccid paralysis (AFP) have been attributed to Guillain-Barré syndrome, an immune-mediated demyelinating disease of peripheral nerves and nerve roots, not spinal gray matter. During the same time period as this study, clinicians in North America (and in some other parts of the world) also noted a sharp increase in hospitalizations for severe acute respiratory illness associated with EV-D68. This study, while not conclusively establishing the etiology of AFM in these reported cases, certainly builds a convincing case that EV-D68 was the likely cause. The precise mechanism by which EV-D68 causes the gray matter lesions is still unclear. While gray matter itself is difficult to sample, the lack of isolation of virus from the CSF suggests that the immune response to EV-D68 may be important in causing AFM.
During the late summer and fall of 2014, cases of acute flaccid myelitis were reported in pediatric patients in the United States. Of 120 cases of acute flaccid myelitis reported, 47% had enterovirus D68 isolated from respiratory secretions when virus isolation was attempted seven days or less after onset of respiratory symptoms.
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