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Heidi Moline, MD1; Anupama Kalaskar, MD2; William F. Pomputius III, MD2; Adriana Lopez, MHS3; Janell Routh, MD3; Cynthia Kenyon, MPH4; Jayne Griffith, MA, MPH4 (

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During September 14–October 1, 2018, the Minnesota Department of Health (MDH) was notified of six children hospitalized in the Minneapolis-St. Paul region with symptoms consistent with acute flaccid myelitis (AFM). A confirmed case of AFM is defined as acute onset of flaccid limb weakness with magnetic resonance image indicating spinal cord lesions largely restricted to gray matter and spanning one or more vertebral segments (1). All six cases were confirmed by CDC. After a cluster of three cases occurred in 2014, an average of fewer than one AFM case per year had been reported to MDH.

Among the six patients, the median patient age was 6.0 years (range = 1.3–9.2 years). All children resided in different Minnesota counties, and all experienced fever and upper respiratory signs and symptoms (e.g., rhinorrhea and cough) beginning a median of 8 days (range = 5–11 days) before weakness onset; none had a history of being immunocompromised. In addition, four patients experienced neck pain or headache, and two experienced diarrhea before weakness onset. Four patients had marked weakness of proximal muscle groups in one arm, although distal motor function was largely preserved. The other two patients initially had weakness in one leg, which became bilateral and rapidly ascended during hospitalization; both of these patients required endotracheal intubation and mechanical ventilation. In all six patients, limb weakness was first noted after waking in the morning. No epidemiologic links among patients were identified.

All six patients were hospitalized. Three patients were discharged home, and two were discharged to inpatient rehabilitation facilities. One patient remains hospitalized with complete paralysis of all voluntary muscles, including the diaphragm, at the time of this report. All discharged patients had residual weakness at time of discharge; among these patients, the median duration of hospitalization was 8 days (range = 1–14 days).

Magnetic resonance imaging (MRI) indicated spinal cord gray matter involvement in all six patients, largely in the anterior horns. The extent of gray matter involvement did not always correlate with deficits seen on physical exam; in three patients with only single limb weakness, multisegment gray matter involvement was apparent. Among all patients, three had anterior nerve root and facial nerve enhancement, and two had basilar and brainstem involvement. Three patients had normal MRI findings early in the illness course, but demonstrated extensive gray matter involvement on a subsequent MRI.

Cerebrospinal fluid (CSF) was collected in five patients, with pleocytosis (white blood cell count >5 cells/mm3) present in two patients (

Five of six patients received some form of immunomodulatory treatment (Table). One patient was treated with steroids and plasmapheresis followed by intravenous immune globulin (IVIG), one with steroids followed by IVIG, three with only IVIG, and one with supportive care only.

This AFM cluster, the largest identified in Minnesota, occurred during a period of increased reporting of AFM nationally and is consistent with the epidemiologic and clinical characteristics of previously described AFM clusters (2–6). Despite report of upper respiratory tract signs and symptoms in all patients, testing for viruses that commonly cause upper respiratory tract infections was positive from nonsterile specimens in only two cases. EV-D68 in the CSF of patient B is considered the cause of AFM in this patient. Detection of a pathogen in the CSF might be related to the severity and prolonged nature of illness in this patient; however, host or other factors contributing to illness severity are unknown.

AFM is a rare but serious cause of sudden onset limb weakness, especially in children, and should be considered in the differential diagnosis. Diagnosis and care of patients with AFM includes early collection of specimens, including CSF, for laboratory testing, MRI scans, and consultation with neurology and infectious disease experts. Potential cases should be reported to public health departments in a timely manner. Public health classification of AFM cases involves expert review of clinical and imaging findings; however, it is important that clinical care not be delayed pending case classification.

Corresponding author: Heidi Moline, hmoline@umn.edu.

1Department of Pediatrics, University of Minnesota Masonic Children’s Hospital, University of Minnesota Medical School, Minneapolis, Minnesota; 2Division of Infectious Disease, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota; 3National Center for Immunization and Respiratory Diseases, CDC; 4Infectious Disease Epidemiology, Prevention and Control Division, Minnesota Department of Health.

All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

References

  • CDC. Acute flaccid myelitis (AFM) 2018 case definition. Atlanta, GA: US Department of Health and Human Services, CDC; 2018. https://wwwn.cdc.gov/nndss/conditions/acute-flaccid-myelitis/case-definition/2018/
  • Messacar K, Schreiner TL, Van Haren K, et al. Acute flaccid myelitis: a clinical review of US cases 2012–2015. Ann Neurol 2016;80:326–38. CrossRef PubMed
  • Maloney JA, Mirsky DM, Messacar K, Dominguez SR, Schreiner T, Stence NV. MRI findings in children with acute flaccid paralysis and cranial nerve dysfunction occurring during the 2014 enterovirus D68 outbreak. AJNR Am J Neuroradiol 2015;36:245–50. CrossRef PubMed
  • Iverson SA, Ostdiek S, Prasai S, et al. ; AFM Investigation Team. Notes from the field: cluster of acute flaccid myelitis in five pediatric patients—Maricopa County, Arizona, 2016. MMWR Morb Mortal Wkly Rep 2017;66:758–60. CrossRef PubMed
  • Bonwitt J, Poel A, DeBolt C, et al. Acute flaccid myelitis among children—Washington, September–November 2016. MMWR Morb Mortal Wkly Rep 2017;66:826–9. CrossRef PubMed
  • Sejvar JJ, Lopez AS, Cortese MM, et al. Acute flaccid myelitis in the United States, August–December 2014: results of nationwide surveillance. Clin Infect Dis 2016;63:737–45. CrossRef PubMed
CharacteristicPatient APatient BPatient CPatient DPatient EPatient F
Age7 yrs7 yrs16 mos3 yrs9 yrs5 yrs
SexMaleFemaleFemaleFemaleFemaleFemale
Previous/Underlying medical conditionsNoneNoneCerebral palsy, seizure disorderCongenital cataractNoneNone
Viral prodrome periodSep 9–11Sep 9–13Sep 17–19Sep 16–18Sep 17–21Sep 21–26
Other symptoms preceding weakness onsetHeadache, vomiting, body achesHeadacheDiarrheaHeadache, neck ache, vomiting, diarrheaNoneNeck ache
Weakness onset dateSep 14Sep 19Sep 22Sep 23Sep 24Sep 29
Weakness siteLeft armLeft legLeft legLeft armRight armRight arm
Hospital admission dateSep 20Sep 19Sep 22Sep 25Sep 28Oct 1
Magnetic resonance Imaging findingsHD 1: NormalHD 1: Enhancement of meninges; gray matter in thoracic cordHD 1: NormalHD 1: NormalHD 1: Enhancement of gray matter in cervical and thoracic cordHD 2: Enhancement of cervical and brainstem gray matter
HD 7: Enhancement of cervical and brainstem anterior horn, cauda equinaHD 8: Improved thoracic cord enhancement; new cervical, cauda equina, and frontal lobe enhancementHD 3: Enhancement of gray matter from cervical cord to cauda equineHD 3: Extensive enhancement of cervical and thoracic anterior horn
Cerebrospinal fluid test resultsHD 1: No pleocytosis; no viral detectionHD 1: Pleocytosis; no virus detectedHD 1: Pleocytosis; no virus detectedHD 1: No pleocytosis; no virus detectedNot collectedHD 1: No pleocytosis; no virus detected
HD 3: Pleocytosis; EV-D68 positive
HD 9: Pleocytosis; no virus detected
Nasopharyngeal swab test resultsHD 7: No virus detectedHD 3: EV-D68 positiveHD 1: No virus detectedHD 1: EV-D68 positiveNot collectedHD 1: No virus detected
HD 10: EV-D68 positive; PEV-A6 positive
TreatmentSteroids, IVIGPlasmapheresis, steroids, IVIGIVIGIVIGNoneIVIG
Hospital courseLeft arm and left facial weakness noted at admission; facial weakness improved; arm weakness with minimal improvement at dischargeRapidly ascending paralysis; respiratory failure; loss of all voluntary motor function; pupillary response intact; cognitively intact; no clinical improvementAscending paralysis; respiratory failure; gradual improvement of weakness; persistent left leg weakness and dysphagia at dischargeLeft arm and left facial weakness at admission; resolution of facial weakness; improved arm weakness at dischargeRight arm weakness at admission; mild improvement of weakness at dischargeRight arm and neck weakness at admission; improvement in neck weakness; minimal improvement of arm weakness at discharge
Discharge dateOct 3Not applicableOct 4Oct 3Sep 29Oct 10
No. of days hospitalized14>90 (ongoing)12919
Discharge locationHomeNot applicableInpatient rehabilitationHomeHomeInpatient rehabilitation

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