Clinical Subpopulations in a Sample of North American Children Diagnosed with Acute Flaccid Myelitis, 2012-2016

Matthew Elrick, Eliza Gordon-Lipkin, Thomas Owen Crawford, Keith Van Haren, Kevin Messacar, Nicole Thornton, Elizabeth Dee, Annie Voskertchian, Jessica Nance, Laura S. Muñoz, Mark P. Gorman, Leslie A. Benson, David L Thomas, Carlos A Pardo-Villamizar, Aaron Milstone, Priya Duggal

Research output: Contribution to journalArticle

Abstract

Importance: Acute flaccid myelitis (AFM) is an emerging poliolike illness of children whose clinical spectrum and associated pathogens are only partially described. The case definition is intentionally encompassing for epidemiologic surveillance to capture all potential AFM cases. Defining a restrictive, homogenous subpopulation may aid our understanding of this emerging disease. Objective: To evaluate the extent to which the US Centers for Disease Control and Prevention (CDC) case definition of AFM incorporates possible alternative diagnoses and to assess the plausibility of a case definition that enriches the biological homogeneity of AFM for inclusion in research studies. Design, Setting, and Participants: Retrospective case analysis of children younger than 18 years diagnosed as having AFM between 2012 and 2016 using the CDC case definition. Group 1 included patients recruited from the United States and Canada based on the CDC case definition of AFM. Group 2 included patients referred to the Johns Hopkins Transverse Myelitis Center for evaluation of suspected AFM. Patients' records and imaging data were critically reviewed by 3 neurologists to identify those cases with definable alternative diagnoses, and the remaining patients were categorized as having restrictively defined AFM (rAFM). Clinical characteristics were compared between patients with rAFM (cases) and those with alternative diagnoses, and a case description distinguishing these AFM groups was identified. Interrater reliability of this description was confirmed for a subset of cases by a fourth neurologist. Data were analyzed between May 2017 and November 2018. Main Outcomes and Measures: Proportion of patients with possible alternative diagnosis. Results: Of the 45 patients who met the CDC AFM case definition and were included, the mean age was 6.1 years; 27 were boys (60%); and 37 were white (82%), 3 were Asian (7%), 1 was Hispanic (2%), and 4 were mixed race/ethnicity (9%). Of the included patients, 34 were classified as having rAFM, and 11 had alternate diagnoses (including transverse myelitis, other demyelinating syndromes, spinal cord stroke, Guillain-Barre syndrome, Chiari I myelopathy, and meningitis). Factors differing between groups were primarily asymmetry of weakness, lower motor neuron signs, preceding viral syndrome, symptoms evolving over hours to days, absence of sensory deficits, and magnetic resonance imaging findings. A case description was able to reliably define the rAFM group. Conclusions and Relevance: We present an approach for defining a homogeneous research population that may more accurately reflect the pathogenesis of the prototypical poliomyelitis-like subgroup of AFM. The definition of rAFM forms a blueprint for inclusion criteria in future research efforts, but more work is required for refinement and external validation.

Original languageEnglish (US)
JournalJAMA Pediatrics
DOIs
StateAccepted/In press - Jan 1 2018

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Myelitis
Centers for Disease Control and Prevention (U.S.)
Transverse Myelitis
Epidemiological Monitoring
Guillain-Barre Syndrome
Spinal Cord Diseases
Motor Neurons
Poliomyelitis
Meningitis
Hispanic Americans
Research
Canada
Spinal Cord

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Clinical Subpopulations in a Sample of North American Children Diagnosed with Acute Flaccid Myelitis, 2012-2016. / Elrick, Matthew; Gordon-Lipkin, Eliza; Crawford, Thomas Owen; Van Haren, Keith; Messacar, Kevin; Thornton, Nicole; Dee, Elizabeth; Voskertchian, Annie; Nance, Jessica; Muñoz, Laura S.; Gorman, Mark P.; Benson, Leslie A.; Thomas, David L; Pardo-Villamizar, Carlos A; Milstone, Aaron; Duggal, Priya.

In: JAMA Pediatrics, 01.01.2018.

Research output: Contribution to journalArticle

Elrick, Matthew ; Gordon-Lipkin, Eliza ; Crawford, Thomas Owen ; Van Haren, Keith ; Messacar, Kevin ; Thornton, Nicole ; Dee, Elizabeth ; Voskertchian, Annie ; Nance, Jessica ; Muñoz, Laura S. ; Gorman, Mark P. ; Benson, Leslie A. ; Thomas, David L ; Pardo-Villamizar, Carlos A ; Milstone, Aaron ; Duggal, Priya. / Clinical Subpopulations in a Sample of North American Children Diagnosed with Acute Flaccid Myelitis, 2012-2016. In: JAMA Pediatrics. 2018.
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abstract = "Importance: Acute flaccid myelitis (AFM) is an emerging poliolike illness of children whose clinical spectrum and associated pathogens are only partially described. The case definition is intentionally encompassing for epidemiologic surveillance to capture all potential AFM cases. Defining a restrictive, homogenous subpopulation may aid our understanding of this emerging disease. Objective: To evaluate the extent to which the US Centers for Disease Control and Prevention (CDC) case definition of AFM incorporates possible alternative diagnoses and to assess the plausibility of a case definition that enriches the biological homogeneity of AFM for inclusion in research studies. Design, Setting, and Participants: Retrospective case analysis of children younger than 18 years diagnosed as having AFM between 2012 and 2016 using the CDC case definition. Group 1 included patients recruited from the United States and Canada based on the CDC case definition of AFM. Group 2 included patients referred to the Johns Hopkins Transverse Myelitis Center for evaluation of suspected AFM. Patients' records and imaging data were critically reviewed by 3 neurologists to identify those cases with definable alternative diagnoses, and the remaining patients were categorized as having restrictively defined AFM (rAFM). Clinical characteristics were compared between patients with rAFM (cases) and those with alternative diagnoses, and a case description distinguishing these AFM groups was identified. Interrater reliability of this description was confirmed for a subset of cases by a fourth neurologist. Data were analyzed between May 2017 and November 2018. Main Outcomes and Measures: Proportion of patients with possible alternative diagnosis. Results: Of the 45 patients who met the CDC AFM case definition and were included, the mean age was 6.1 years; 27 were boys (60{\%}); and 37 were white (82{\%}), 3 were Asian (7{\%}), 1 was Hispanic (2{\%}), and 4 were mixed race/ethnicity (9{\%}). Of the included patients, 34 were classified as having rAFM, and 11 had alternate diagnoses (including transverse myelitis, other demyelinating syndromes, spinal cord stroke, Guillain-Barre syndrome, Chiari I myelopathy, and meningitis). Factors differing between groups were primarily asymmetry of weakness, lower motor neuron signs, preceding viral syndrome, symptoms evolving over hours to days, absence of sensory deficits, and magnetic resonance imaging findings. A case description was able to reliably define the rAFM group. Conclusions and Relevance: We present an approach for defining a homogeneous research population that may more accurately reflect the pathogenesis of the prototypical poliomyelitis-like subgroup of AFM. The definition of rAFM forms a blueprint for inclusion criteria in future research efforts, but more work is required for refinement and external validation.",
author = "Matthew Elrick and Eliza Gordon-Lipkin and Crawford, {Thomas Owen} and {Van Haren}, Keith and Kevin Messacar and Nicole Thornton and Elizabeth Dee and Annie Voskertchian and Jessica Nance and Mu{\~n}oz, {Laura S.} and Gorman, {Mark P.} and Benson, {Leslie A.} and Thomas, {David L} and Pardo-Villamizar, {Carlos A} and Aaron Milstone and Priya Duggal",
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AU - Elrick, Matthew

AU - Gordon-Lipkin, Eliza

AU - Crawford, Thomas Owen

AU - Van Haren, Keith

AU - Messacar, Kevin

AU - Thornton, Nicole

AU - Dee, Elizabeth

AU - Voskertchian, Annie

AU - Nance, Jessica

AU - Muñoz, Laura S.

AU - Gorman, Mark P.

AU - Benson, Leslie A.

AU - Thomas, David L

AU - Pardo-Villamizar, Carlos A

AU - Milstone, Aaron

AU - Duggal, Priya

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N2 - Importance: Acute flaccid myelitis (AFM) is an emerging poliolike illness of children whose clinical spectrum and associated pathogens are only partially described. The case definition is intentionally encompassing for epidemiologic surveillance to capture all potential AFM cases. Defining a restrictive, homogenous subpopulation may aid our understanding of this emerging disease. Objective: To evaluate the extent to which the US Centers for Disease Control and Prevention (CDC) case definition of AFM incorporates possible alternative diagnoses and to assess the plausibility of a case definition that enriches the biological homogeneity of AFM for inclusion in research studies. Design, Setting, and Participants: Retrospective case analysis of children younger than 18 years diagnosed as having AFM between 2012 and 2016 using the CDC case definition. Group 1 included patients recruited from the United States and Canada based on the CDC case definition of AFM. Group 2 included patients referred to the Johns Hopkins Transverse Myelitis Center for evaluation of suspected AFM. Patients' records and imaging data were critically reviewed by 3 neurologists to identify those cases with definable alternative diagnoses, and the remaining patients were categorized as having restrictively defined AFM (rAFM). Clinical characteristics were compared between patients with rAFM (cases) and those with alternative diagnoses, and a case description distinguishing these AFM groups was identified. Interrater reliability of this description was confirmed for a subset of cases by a fourth neurologist. Data were analyzed between May 2017 and November 2018. Main Outcomes and Measures: Proportion of patients with possible alternative diagnosis. Results: Of the 45 patients who met the CDC AFM case definition and were included, the mean age was 6.1 years; 27 were boys (60%); and 37 were white (82%), 3 were Asian (7%), 1 was Hispanic (2%), and 4 were mixed race/ethnicity (9%). Of the included patients, 34 were classified as having rAFM, and 11 had alternate diagnoses (including transverse myelitis, other demyelinating syndromes, spinal cord stroke, Guillain-Barre syndrome, Chiari I myelopathy, and meningitis). Factors differing between groups were primarily asymmetry of weakness, lower motor neuron signs, preceding viral syndrome, symptoms evolving over hours to days, absence of sensory deficits, and magnetic resonance imaging findings. A case description was able to reliably define the rAFM group. Conclusions and Relevance: We present an approach for defining a homogeneous research population that may more accurately reflect the pathogenesis of the prototypical poliomyelitis-like subgroup of AFM. The definition of rAFM forms a blueprint for inclusion criteria in future research efforts, but more work is required for refinement and external validation.

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