Three Articles About AFM Published in JAMA Pediatrics

On November 30th, The Journal of the American Medical Association (JAMA) Pediatrics published three articles about acute flaccid myelitis (AFM). One article, “A Parental Perspective on Strengthening Knowledge After Acute Flaccid Myelitis,” was written by three mothers of children with AFM, Dr. Riley Bove, Heather Werdal, and Erin Olivera.1 They discuss their experiences caring for their children, as well as supporting other parents faced with this diagnosis through a Facebook group for parents of children with AFM. They explained that when they brought their children to a physician for evaluation of weakness, the physicians often did not perform a neurological examination that would have revealed the limb weakness. Often, they dismissed this weakness as insignificant, which led to delays in diagnostic tests and treatment “…The delay in evaluation represented the first of a series of schisms between us and the health care system that eroded our trust that our children’s cases were taken seriously, reported to the CDC adequately, and followed up with care.” They also note their ongoing role as caregivers for their children and the need to deal with complications, such as scoliosis and pain. They urge medical providers to advocate for greater insurance allowances for rehabilitation, and a greater willingness to work with their children’s schools and therapists. The authors write, “We share this perspective with the hope that early awareness, intervention, and advocacy will prevent AFM from becoming more common and will help our affected children achieve a future where they are not defined by their AFM.”

Earlier this fall, several clinicians and health care providers established the AFM Working Group. The Group consists of medical professionals and researchers from approximately 25 institutions and is under the leadership of Dr. Carlos Pardo from the Johns Hopkins Transverse Myelitis Center. The TMA is a member of this working group, and is committed to advancing the knowledge, research and education regarding AFM.  Dr. Sarah Hopkins, Dr. Matthew J. Elrick, and Dr. Kevin Messacar, in partnership with the working group, wrote an article about the diagnosis, treatment, and future directions for AFM.2 They discuss key diagnostic features found through lumbar puncture and magnetic resonance imaging (MRI) of the spinal cord. They discuss the identification of infections associated with AFM, such as enterovirus D68 and enterovirus A71. They argue that when AFM is suspected, patients should be hospitalized with a concern for the progression of weakness or loss of the ability to breathe. They discuss potential treatment options and note that intravenous immunoglobulin (IVIG) has been widely used, but that there are mixed opinions about the use of steroids or plasma exchange. They argue that “this is an area in urgent need of further research” and note the importance of early and continued rehabilitation.

Following outbreaks of AFM in 2012 and 2014, the U.S. Centers for Disease Control and Prevention (CDC) and the Council of State and Territorial Epidemiologists created a standardized case definition for this illness which could be used for epidemiological surveillance.3 This definition has been used by clinicians to diagnose and treat children presenting with this illness and by scientists to define research cohorts. While the CDC’s definition has been used to identify cases for the purpose of surveillance, it may need to be refined so as not to encompass other rare neuro-immune disorders, such as transverse myelitis, Guillain-Barre syndrome, spinal cord stroke, acute disseminated encephalomyelitis, MOG antibody-associated disease, and other myelopathies.

Researchers, many of whom are part of the AFM working group, conducted a retrospective analysis which included the cases of 45 children younger than 18 who were diagnosed with AFM in the United States and Canada between 2012 and 2016. The records came from patients who self-referred or were referred by their physicians for a study of genetic susceptibility to AFM, and patients presenting with suspected AFM to the Johns Hopkins Transverse Myelitis Center between 2014 and 2017. The two goals of the study were to determine whether the CDC case definition of AFM includes patients with different diagnoses and to identify clinical characteristics that differentiate AFM from other diagnoses. Neurologists reviewed the medical records and MRIs (when available) of all patients and categorized them as either patients with “AFM with possible alternative diagnosis” (AFM-ad) or patients who met only the CDC case definition for AFM and no other alternative diagnosis, which they called “restrictively defined AFM”, or rAFM. The researchers then compared each clinical variable in the patients’ medical records to generate a description of rAFM; those characteristics that were present in all patients in the rAFM group. None of these characteristics were present in patients in the AFM-ad group. To further refine the rAFM case description, a blinded independent neurologist reviewed randomly selected cases, and the description was updated based on this review.

The researchers found that 34 patients had a diagnosis consistent with rAFM while 11 patients had a diagnosis classified as AFM-ad. The most common alternative diagnoses for the AFM-ad patients were transverse myelitis and spinal cord ischemia (spinal cord stroke). The researchers identified four major characteristics shared by all rAFM patients. They also identified several key differences between rAFM and AFM-ad. These included differences in the pattern of limb involvement (rAFM cases were more likely to have an asymmetric onset and less likely to have both legs affected). rAFM cases were more likely to have decreased muscle tone, and less likely to have bladder and bowel issues, or sensory issues. AFM-ad cases were more likely to have an onset that reached its peak in less than an hour. rAFM cases were more likely to have an infection prior to the onset of symptoms. The researchers also found differing diagnostic and imaging characteristics between the groups. For example, rAFM cases were more likely to have gray matter predominant lesions in the spinal cord than AFM-ad cases.

The researchers suggest that their findings lend to a more well-defined case definition for AFM that should be used as a starting point for inclusion and exclusion criteria in research. Additionally, their findings may be used in the clinical setting to more quickly and accurately diagnose AFM, so that treatment can be administered immediately, and patients can be monitored for respiratory issues. Early diagnosis of AFM enables a better chance of identifying a pathogen in biological samples, and it may also provide prognostic information to guide long-term treatment and rehabilitation. While the researchers’ case definition of AFM may be useful in the clinical setting, it may be problematic for a small number of cases and should not automatically exclude all cases that don’t meet these criteria.

The authors of the study acknowledge that a major limitation of this study is the inability to independently validate the use of the proposed description of rAFM. Such validation would require a separate and prospectively defined cohort of children presenting with acute weakness including other pathologies, such as ischemic myelopathies. They also state that the criteria described is provisional and expect that an iterative process of refinements can better serve the research needs of the AFM community.

[1] Bove R, Werdal H, Olivera E. A Parental Perspective on Strengthening Knowledge After Acute Flaccid Myelitis. JAMA Pediatr. 2018 Nov 30.

[2] Hopkins SE, Elrick MJ, Messacar K. Acute Flaccid Myelitis-Keys to Diagnosis, Questions About Treatment, and Future Directions. JAMA Pediatr. 2018 Nov 30.

[3] Elrick MJ, Gordon-Lipkin E, Crawford TO et al. Clinical Subpopulations in a Sample of North American Children Diagnosed With Acute Flaccid Myelitis, 2012-2016. JAMA Pediatr. 2018 Nov 30.

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