Acute Flaccid Myelitis: Cause, Diagnosis, and Management


Since 2012, there has been an alarming bi-annual pattern of increases in the number of acute flaccid myelitis (AFM) cases. Although the disorder that we now know of as AFM is not new, the bi-annual spikes, linked to an ordinarily innocuous enterovirus, have raised questions and alarm from a public health perspective. Following the increase in cases in 2018, a group of clinicians and researchers around the United States established The AFM Working Group (AFMWG). This multicentric and multidisciplinary group, led by Dr. Carlos A. Pardo from Johns Hopkins University, was formed and included health care providers, clinicians, and researchers from more than 25 institutions, and patient advocacy groups (such as the Siegel Rare Neuroimmune Association) to address the clinical needs of patients, families, and to support further research. The group began to outline consensus guidelines for improving diagnosis, developing management strategies of clinical concerns found in AFM, coordinating research efforts, and prioritizing research needs. This multi-disciplinary approach of clinicians, scientists, public health agencies, advocacy groups, and families was necessary and innovative. Building consensus from various yet shared experiences of this rare disorder, which at first had no clinical trials or treatment protocols available, has led to a collaborative and comprehensive effort.

This effort has resulted in the first consensus publication of clinical guidance on AFM in the medical journal, The Lancet. Dr. Olwen Murphy, a former James T. Lubin Fellow of the Siegel Rare Neuroimmune Association, led the publication of “Acute flaccid myelitis: cause, diagnosis, and management.” This paper summarizes the critical and substantial work of the AFMWG. From definite to uncertain diagnosis, the authors provide a detailed and comprehensive clinical perspective necessary for medical professionals and families to recognize the symptoms, accurately diagnose, establish acute treatment protocols, as well as near and long-term rehabilitation and recovery strategies for those with AFM.

It is the clinical definition of AFM that this paper sets forth that treating physicians and families should seek to understand when establishing whether or not a child has AFM. The paper breaks down the timeline of an AFM diagnosis from recognition to recovery, outlining recommended protocols for each stage of the diagnosis, and underscores the importance of further studies to aid our understanding of the precise and various disease mechanisms by which an individual ends up with AFM.

It is only through consistent and widely used clinical diagnostic guidelines, treatment plans, and the collection of essential specimens and data that we can begin to understand who will develop AFM after a viral infection and how we can stop it from developing. We can continue to increase awareness, improve on ensuring patients get an accurate diagnosis, and swiftly implement appropriate treatment and rehabilitation strategies to enhance recovery and quality of life of those with AFM.

As the COVID-19 pandemic introduced several emergency public health measures around the world including physical distancing, lockdowns and quarantines, the circulation of other viruses including enteroviruses, the viruses involved as a cause of AFM, decreased dramatically. However, it is expected that once the public health measures around COVID-19 are relaxed and children return to normal school activities in 2021 and 2022, new outbreaks of AFM will emerge. This paper sets up preparedness for such possible outbreaks and focuses on education and awareness for healthcare providers to improve diagnosis and management of AFM.

Members of the AFMWG, including Drs. Carlos Pardo and others, will be presenting about this paper during a Town Hall webinar in January 2021, details will be announced on the SRNA website. They’ll be discussing various details of the paper, their work as a collaborative group, and why the approach they’ve taken to work collaboratively was necessary. They’ll be available to clinicians and families alike to answer questions on the clinical diagnosis and treatment plans for AFM and help advance understanding and research of AFM.

What we now call AFM today was previously considered under the umbrella of transverse myelitis (TM), specifically as a subtype of this disorder. The similarities between the two can be vast, but the two often overlap, from treatment options to long-term management strategies. The more we understand about AFM, the better we will understand other rare neuroimmune disorders like TM, acute disseminated encephalomyelitis (ADEM), MOG antibody disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and optic neuritis (ON).

About The AFM Working Group

The AFM Working Group was established in North America in September 2018 in response to the emergence of AFM as a disabling disease representing a significant public health threat. With a total of 131 group members, it encompasses a wide range of relevant specialties including neurology, pediatrics, infectious diseases, critical care medicine, surgery, and physical medicine & rehabilitation, as well as scientists with expertise in epidemiology, genetics, virology and immunology, and representatives from the patient community. The mission of The AFM Working group is to develop, generate consensus, and share knowledge about the disease for the welfare of individuals diagnosed with AFM in the United States and around the world.

For more information, please visit

About SRNA

Siegel Rare Neuroimmune Association was founded 25 years ago by families of loved ones affected by rare neuroimmune disorders. We advocate for, support and educate individuals and their families diagnosed with rare neuroimmune disorders – acute disseminated encephalomyelitis, acute flaccid myelitis, MOG antibody disease, neuromyelitis optica spectrum disorder, optic neuritis and transverse myelitis. We invest in scientific research, therapy development and training of clinician-scientists dedicated to these disorders. We have over 15,000 members and are active in 121 countries. We offer an up-to-date accurate website, resource library of over 300 publications, a patient registry, “Ask the Expert” podcasts, education symposia, the Myelitis Helpline, Quality of Life Family camps, clinician-scientist training Fellowship and a support group network. SRNA is a registered nonprofit organization recognized by the U.S. Internal Revenue Service as a 501(c)(3) non-profit organization with a Guidestar Silver Seal of Transparency.

For more information, please visit

Other links:

From the CDC

SRNA AFM Hope Ambassadors


Carlos A. Pardo, MD ([email protected])

Andrea Salazar, MD ([email protected])

Evidence Related to COVID-19 in People Living with Spinal Cord Injury

Recently, the North American Spinal Cord Injury Consortium (NASCIC) published a summary of several studies regarding COVID-19 and people living with spinal cord injury (SCI). Although our community members may have additional concerns due to their rare neuroimmune diagnosis, the findings can still be helpful to our community members who have non-traumatic spinal cord injury. We are still learning the effects that COVID-19 may have on our community, and studies such as the these are helpful in creating a clearer picture. Below is the conclusion of the NASCIC’s summary of the studies on COVID-19 and SCI. The full summary of the NASCIC’s findings, including take home messages and additional resources, can be found here.

“Since the onset of the COVID-19 pandemic, the unknown has caused significant impact in the community living with spinal cord injury (SCI). At the same time, there has been much learning, creation, and gathering of knowledge and resources about this disease to begin to understand the SCI community’s health risks in relation to COVID-19. The North American Spinal Cord Injury Consortium (NASCIC) took the initiative to gather and present all current evidence-based information and knowledge about COVID-19 related to those living with SCI. NASCIC collaboratively assessed various resources to provide those living with SCI and the community a thorough understanding of the current situation and, hopefully, quell fears of the unknown related to COVID-19. The evidence that NASCIC has compiled and has included in this report covers:

  • the concerns about the pandemic from people with SCI,
  • case studies with SCI who have contracted COVID-19, and
  • impacts of nationwide lockdowns due to COVID-19.

NASCIC additionally highlights preliminary best-practices people with SCI can take to stay safe and healthy (physically, mentally, and emotionally) as they live through the pandemic. Research involving COVID-19 and its effect on the community are on-going and NASCIC hopes that this report will help bring awareness and open doors for further conversation and advocacy about the concerns/needs of the SCI community to researchers, policy makers, healthcare providers, and other stakeholders with interest in spinal injury. This report and take-home points will be updated as new, peer-reviewed evidence becomes available.

Based on the review presented of the evidence available at the time of publishing, it is fair to say that so far, the SCI community does not necessarily experience more severe symptoms and mortality if COVID-19 is contracted compared to the rest of the population.

However, due to the SCI community’s need for personal care, they do face an added risk in being exposed to the virus. Personal care attendants may not be able to socially distance themselves when assisting individuals, and thus create an added risk in transmitting or contracting the virus. This added risk can be reduced through appropriate usage of personal protective equipment (PPE). Hand washing and personal safety with PPE are an absolute priority, as it can help lower risk of spread. Lastly, like everyone experiencing the pandemic, mental and emotional health are impacted. Hence, it is a great time to virtually connect with one’s family and friends and find new support groups online to help cope with isolation.

Further conversation and continuous advocacy for the SCI community is NASCIC’s focus during this unprecedented time. NASCIC encourages meaningful engagement and further education as we endure this pandemic. We look forward to sharing the results of ongoing and future studies that are being conducted that address the impact of COVID-19 on the SCI community.”

North American Spinal Cord Injury Consortium, Evidence Related to COVID-19 in People Living With Spinal Injury. Niagara Falls, NY. 2020.

Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders

Many individuals with rare neuroimmune disorders may be concerned about their risk of COVID-19 and whether they are at higher risk of severe disease than those without a rare neuroimmune disorder. Louapre and colleagues conducted a study with those with neuromyelitis optica spectrum disorders (NMOSD) and MOG antibody disease (MOGAD) who had a confirmed diagnosis of COVID-19 or a highly suspected diagnosis of COVID-19. They included 15 patients from 11 centers in France.

5 patients were aquaporin-4 antibody positive, 5 were MOG antibody positive, and 5 were negative for both antibodies. All 15 patients were on some medication to reduce the risk of relapses, which included 9 patients on rituximab, 1 on ofatumumab, 2 on azathioprine, and 3 on mycophenolate mofetil.

The most common COVID-19 symptoms they experienced were weakness/lack of energy (80%), fever (66.7%), cough (46.7%), loss of smell or taste (46.7%) headache (40%), difficulty breathing (40%), and digestive issues (40%). 5 of the 15 patients required hospitalization, with 2 needing oxygen support. All 5 of those who were hospitalized were on rituximab. One patient, a 24-year-old who was on rituximab, was on mechanical ventilation in the ICU for 44 days, and their only reported potential risk factor for severe disease was a BMI of 40. Overall, those who were treated as outpatients were younger, had a lower disability score, and had a longer disease duration than those who needed to be hospitalized. Those who were hospitalized had received a rituximab infusion more recently (median time from last infusion was 3 months) than those who were not hospitalized (5 months).

Dr. Benjamin Greenberg, a member of SRNA’s Board of Directors and Medical and Scientific Council noted: “This paper adds to our understanding of the impact of COVID on our rare disease patient population. While we cannot draw firm conclusions about the relative risk for developing complications from COVID-19, there are trends in the literature associating higher rates of hospitalizations with anti-CD20 therapies (like rituximab). Further research is required to determine if this association is real and if there is a cause for concern in patients taking these medications.” 

You can find more information on COVID-19 and rare neuroimmune disorders on our information page here.

Preliminary Findings from The SRNA Registry

In 2017, SRNA created a patient registry. The purpose of the registry is to help advance research about rare neuroimmune disorders, collaborate with researchers from around the world, and identify participants for clinical trials. Many of our members have shared information about their diagnosis, treatment, and outcomes over the years.  The information our community has shared continues to help us guide our programs and research, and we are grateful to all who have participated.

The SRNA registry has been designed to learn more about the natural history of rare neuroimmune disorders, treatments, and outcomes using standardized tools. In June of this year, we reviewed the data from the registry to analyze trends and identify points for follow-up examination and research. Below are some of the preliminary findings.

As of June 2020, there were 496 participants in the registry. 74% of respondents were diagnosed with transverse myelitis, 9% were diagnosed with neuromyelitis optica spectrum disorder, 5% were diagnosed with acute disseminated encephalomyelitis, 4% were diagnosed with acute flaccid myelitis, 4% were diagnosed with MOG antibody disease, and 2% were diagnosed with another disease or have yet to receive a diagnosis.

40% of participants in the registry were diagnosed less than one week after symptom onset, 22% were diagnosed within 1-3 weeks, and 7% were diagnosed within 4-6 weeks. 30% of participants received a diagnosis more than six weeks after symptom onset. 1% were unsure or did not know how long it took to receive a diagnosis.

84% of participants received treatment after their first acute attack. However, only 30% of participants received a second treatment that was different than the first, and 11% of participants were unsure or did not know if they received a second treatment. Most (80%) participants received rehabilitative therapy.

For current symptoms, 82% of participants currently have weakness or paralysis, 81% of participants currently have numbness or loss of sensation, and 64% of participants have spasticity or uncontrolled muscle spasms. 54% experience neck or back pain, 77% of participants experience neuropathic pain, and 71% of participants have bladder and/or bowel symptoms.

These results show that the majority of patients did not receive a quick diagnosis (less than a week) after their onset of symptoms, which can delay the administration of acute treatments. Time is critical in the early stages of a rare neuroimmune inflammatory attack, so quicker diagnoses are needed to start acute treatments and prevent damage to the central nervous system. Further, less than one third of participants in the registry received a second acute treatment during their initial inflammatory attack. While more research is needed to determine the effectiveness of a second form of acute treatments, steroids, plasmapheresis (PLEX), IVIG, and cyclophosphamide have all been used during the onset of these disorders.

Rehabilitation is important for restoring function following a rare neuroimmune diagnosis. While 80% of the participants received rehabilitative therapy, 20% of participants did not receive any rehabilitation following their diagnosis. Further advocacy is needed to educate physicians and medical professionals on the importance of rehabilitation following these disorders.

The majority of participants experience lasting symptoms following their diagnosis of a rare neuroimmune disorder, including weakness, paralysis, numbness, pain, spasticity, bladder dysfunction, and bowel dysfunction. While there are currently a variety of methods for treating these symptoms, more research is needed to improve the quality of life for these individuals and find stronger solutions for symptom management.

If you would like to participate in the SRNA Registry, please visit the study page to learn more and fill out this form to sign up.

Cytokine biomarkers associated with acute flaccid myelitis

Original publication: William C. Weldon, Kun Zhao, Heather A. Jost, Kimbell Hetzler, Jessica Ciomperlik-Patton, Jennifer L. Konopka-Anstadt, M. Steven Oberste. Cytokine biomarkers associated with clinical cases of acute flaccid myelitis. Journal of Clinical Virology 131 (2020) 104591.

Acute Flaccid Myelitis (AFM) is a neurological condition characterized by a rapid onset of flaccid muscle weakness, with associated abnormalities on imaging of the spinal cord (MRI). This disease predominantly affects the gray matter of the spinal cord in children and is usually preceded by a febrile illness which has been linked to an infectious disease produced by a respiratory virus, enterovirus D-68. Weldon and his colleagues recently published in the Journal of Clinical Virology, an analysis of the expression of immune proteins called cytokines and chemokines in patients affected by AFM. Cytokine and chemokines are mediators of inflammation as they regulate the function and trafficking of immune cells in the body and are particularly important during stages of inflammation or response to infections. They are particularly important for the understanding of AFM as they may play a role in the process of inflammation that targets the spinal cord.

The investigators tested paired samples of cerebrospinal fluid (CSF) and serum obtained from 70 confirmed AFM patients as defined by the CDC criteria and 47 non-AFM control subjects with other diseases. The goal of the study was to determine if there are any specific signals that distinguish the cytokine and chemokine response observed in patients with AFM as compared with controls, responses which may provide clues about the pathogenesis of AFM. All cases of AFM were defined as ’confirmed’ when magnetic resonance imaging (MRI) showed predominantly gray matter lesions spanning at least one or more segments of the spinal cord –, and

The study analyzed the levels of these cytokines and chemokines in confirmed AFM and non-AFM patients, and also compared between limb weakness vs. no limb weakness and those who were positive for enterovirus and not. The study found several cytokines that were observed to be increased in the CSF of AFM-positive patients compared to non-AFM cases which were unique to those samples positive for enterovirus and limb weakness.  Two pro-inflammatory cytokines/chemokines called IP- 10 and IL-6 were significantly elevated in AFM patients compared to non-AFM patients.

In the central nervous system, IP-10 has been associated with other illnesses induced by viral infections, and elevated IL-6 is expressed in neuroimmune conditions such as neuromyelitis optica spectrum disorder and also has been shown to be high in viral infections of the CNS such as Zika virus. The findings of the study by Weldon and collaborators add further evidence of the active and aggressive inflammatory damage the spinal cord suffers in patients affected by AFM. While there were limitations in the study sampling and unmatched controls were used, the results of the study reveal the need for further examination of the pathogenic mechanisms leading to the extensive damage of motor neurons that affect AFM patients. Future prospective natural history studies of AFM may need to confirm these preliminary observations to determine if the modulation of these specific cytokines/chemokines may be of therapeutic value and also to investigate with more detail the role that cytokines and chemokines may play in the mechanisms that lead to spinal cord damage in AFM.

This summary of the peer-reviewed publication in Journal of Clinical Virology was reviewed by Dr. Carlos A. Pardo, Professor of Neurology at Johns Hopkins University and Director of the Johns Hopkins Myelitis and Myelopathy Center and includes his views on the importance of this study.

Alexion to Begin Soliris Trial for Pediatric Patients with NMOSD

Alexion Pharmaceuticals is conducting a Phase 2/3 study to evaluate the safety and efficacy of eculizumab (Soliris) specifically in pediatric participants with relapsing neuromyelitis optica spectrum disorder (NMOSD).

This study is an interventional, open-label, single-arm trial for pediatric individuals aged 2 to 17 years with anti-aquaporin-4 antibody-positive NMOSD. It is open to participants in Japan, Korea, Spain, and the United States. All locations are currently recruiting except Korea at the time of this writing.

Dosing of eculizumab will be based on the participant’s body weight, and as such, as weight may change, so may the participant’s weight cohort and dosing. Beginning with a weight-based weekly dose of eculizumab during an induction phase, participants will receive intravenous infusion every two weeks during the Primary Treatment Period for a total of 52/53 weeks. After completing the Primary Treatment Period, participants may continue to receive eculizumab in the Extension Treatment Period for 104 weeks.

Notable inclusion criteria in addition to the anti-AQP4 antibody positivity and a confirmed NMOSD diagnosis, participants must be age 2 to 17 years (must be less than 18 years) and with a bodyweight greater than or equal to 10 kilograms (or 22.0462 pounds). Participants should have experienced at least two relapses in the past two years, with at least 1 of the relapses occurring in the past year before screening. Those who participate in the study and also receive supportive immunosuppressive therapies to prevent relapse, whether in combination or as a single therapy, must be on a stable dosing regimen for a long enough amount of time.

Exclusion criteria include those with unresolved or chronic infections that have not been appropriately treated with antibiotics, or prior to screening have used rituximab or other biologicals within six months, mitoxantrone within three months, IVIG or plasma exchange (PLEX) within three weeks, or immunomodulatory therapies for multiple sclerosis (MS) within three months.

Those interested in this study may find the full inclusion/exclusion criteria here and here and should contact Alexion Pharmaceuticals by phone, +1 855-752-2356, or by email at [email protected].

Ignition Survey for MOGAD Results

In Spring 2020, The MOG Project partnered with the Siegel Rare Neuroimmune Association and The Sumaira Foundation for NMO to understand treatment practices among those with MOG antibody disease (MOGAD). The intention of the survey was to learn from the MOGAD community experience and share results with physicians and each other.

267 individuals with MOGAD and their caregivers completed a survey asking a range of questions regarding acute and preventive treatments and their associated side effects. 89% of respondents had been prescribed an acute treatment during their most recent attack/relapse, the most commonly prescribed being IV Steroids (86%) followed by Oral Steroids (50%). Nearly 70% of those diagnosed with MOGAD are currently on a preventive treatment. Rituximab (45%), Mycophenolate Mofetil (25%) and IVIG (25%) were cited as commonly prescribed preventive treatments. Side effects were common, with 66% of respondents reporting side effects from their acute treatments. 49% of those on Rituximab, 32% on Mycophenolate Mofetil, and 53% on IVIG reported side effects from their treatments.

It is important to note that this respondent pool may skew towards patients with more severe cases of MOGAD, as these people may have been more likely to respond to the survey. You can view the detailed survey results here. Special thanks to the members of the MOGAD community and their caregivers for participating in this survey. It is our hope that these survey results help those affected by MOGAD know they are not alone; ours is a shared experience as a community.

Update on UT Southwestern Q Cell Stem Cell Trial in Transverse Myelitis

During these unprecedented times of COVID-19 we have fielded many questions about the impact of the pandemic on our clinics, health care systems and patients. I hope everyone has been able to stay safe during these days of isolation and social distancing. While I am confident that a solution to the COVID-19 pandemic will be found, the impact of these events will be felt for years.

Beyond the personal health impacts, economic impacts and changes to our medical system, the pandemic has dramatically impacted basic science and clinical research efforts across the world. The UT Southwestern Q Cell Stem Cell trial is included. Since the mandates to enact social distancing were put into effect, basic science labs and clinical trials were paused. Thus, we have been unable to proceed with our first surgery as planned. Based on the number of questions received, we wanted to provide this update to our community.

We have received FDA clearance to proceed with this phase one trial in paralyzed TM patients. The trial currently plans to enroll nine patients for the surgical implantation of Q Cells. This is a safety study with many regulatory requirements, including a requirement focused on training the surgical team to perform the procedure with novel technology. As we worked during the year to get complete licensing and credentialing requirements for the team, the COVID-19 pandemic began, halting plans for first enrollment and surgery.

Nevertheless, we are preparing to reopen for research at UT Southwestern. As such, we continue to work to identify the nine candidates for this clinical trial. Those interested can find information on the SRNA website. We appreciate your support during these difficult times and remain excited about what lies ahead.

Benjamin M. Greenberg, MD, MHS, FANA, FAAN
Director, Perot Foundation Neurosciences Translational Research Center
O’Donnell Brain Institute
University of Texas Southwestern
Board of Directors, Siegel Rare Neuroimmune Association (Formerly the Transverse Myelitis Association)

Dr. Greenberg has received funding from the SRNA and serves as an unpaid member of the board of the SRNA.

Case Report: Transverse Myelitis following COVID-19

A case report was recently published of a 60-year-old man who received a diagnosis of transverse myelitis after infection with SARS-CoV2, which is the coronavirus that has been spreading throughout the world. He was admitted to the hospital with respiratory symptoms and was given a throat swab test that showed he was positive for the virus. He recovered from COVID-19 pneumonia and was sent home after five days. Three days later, he was unable to urinate and had weakness in his legs. The man was unable to walk unassisted and had other signs of spinal cord dysfunction. An MRI of his spine showed a lesion at T9 consistent with myelitis. He had no lesions in the brain. He had a spinal tap which showed that his cerebrospinal fluid had an increased cell count and protein levels, also consistent with myelitis. The coronavirus (SARS-CoV2) was not found in his cerebrospinal fluid, and all other testing for other bacteria and viruses was negative.

He was treated with an intravenous antiviral medication and an antibiotic, but this treatment was stopped after 8 days when no infectious agents were found in his cerebrospinal fluid. He improved slightly after three days. On the 7th day, he was given a lower dose of steroids than is typically given in transverse myelitis because of the known prior infection with the virus. He then improved rapidly. He was discharged after 13 days with some sensation impairments, but he had normal bladder function and was able to walk independently. The authors of the report believe this was not the case of a direct infection of SARS-CoV-2 into the spinal cord, but an overreaction of the immune system to the virus (i.e., post-infectious myelitis).

We will continue to monitor cases of neuroimmune issues after COVID-19 and will share with our community as we hear about them. For additional information, please visit our COVID-19 page.

Munz M, Wessendorf S, Koretsis G, et al. Acute transverse myelitis after COVID-19 pneumonia. J Neurol. 2020 May 26;1-2.

Survey about Disability Identity Development

Over the past five years, Anjali Forber-Pratt, PhD, has been working to develop and validate a measure of disability identity development. While the study has made a lot of progress, it is in need of another sample of approximately 1,000 individuals with disabilities to complete the reduced set of items. This is a one-time email as we would like to invite you to participate in the study by taking the following survey, which contains a significantly reduced set of questions:

The survey will take no more than 20 minutes to complete and contains basic questions about yourself, your disability, your interactions with others, your involvement with the disability community and perceptions about your identity. If you choose to participate, you may enter your contact information (or you may opt out by not entering it) to enter a drawing for a $100 Amazon gift card. Three gift cards will be drawn. Your participation in this study is voluntary. In order to be eligible to participate in this study, you must be:

  • 18 years of age or older
  • Identify as having a disability (visible or hidden)
  • Able to reliably complete self-report measures in English
  • Living or residing in the United States

Thank you for your consideration! Feel free to share with others who may be eligible to participate. Email [email protected] with any questions.

Anjali J. Forber-Pratt, Ph.D. is an Assistant Professor at the Department of Human & Organizational Development at Vanderbilt University. Her research agenda adopts a social-ecological framework and looks at issues surrounding identity, equity and empowerment through methodology for individuals who are different in some way, with a large focus on disability. She completed her degrees at the University of Illinois. Dr. Forber-Pratt is a Paralympic medalist and currently serves as a member of the Board of Directors of SRNA.