The five parts of the symposium covered a breadth of topics on AFM diagnosis and acute management, critical care management, understanding pathogenesis, viruses and immunity, long-term management of AFM, and orthopedic and surgical treatments for AFM. We summarize and highlight some of the key lessons we have learned from leaders in the community who have dedicated their careers to understanding AFM and helping families and children. All sessions were recorded and are available here.
Dr. Kevin Messacar from Children’s Hospital Colorado commenced the first session and offered an overview of our current understanding of AFM. He was followed by Rachel Scott, co-founder of the Acute Flaccid Myelitis Association (AFMA), who shared her powerful story and experience with her son Braden’s AFM diagnosis, who was diagnosed in July 2016. Dr. Janell Routh from CDC shared that the last six years of surveillance data have showed us that although we have a consistent low baseline level of AFM cases every year, something definitely changed in 2014 and we started seeing a peak of AFM cases every 2 years, mostly during late summer/early fall. This change seems to be related to the circulation of enterovirus-D68 (EV-D68). Dr. Charles Chiu at University of California San Francisco spoke about the connection between AFM and EV-D68 and EV-A71, which are viruses that were identified from respiratory secretions prior to the onset of the weakness from samples of children diagnosed with AFM. He reminded us that diagnosis in AFM is challenging, especially if we want to be able to identify the viruses in blood or other samples, as most of the time we are not able to find it in these samples. He expressed the importance of creating and investing in new methods of diagnosis that are faster and more accurate. Then, the impact of social distancing measures of the COVID-19 pandemic on AFM was discussed by Dr. Bryan Grenfell and Daniel Park. It will likely delay and perhaps even increase the susceptibility of the population to the virus, with the possibility of a larger outbreak in the future.
Drs. Elizabeth Wells (Children’s National), Sarah Hopkins (Children Hospital of Philadelphia), and Leslie Benson (Boston Children’s Hospital) all reiterated for pediatricians and emergency room (ER) doctors across the country to think about AFM when they see a child with weakness and emphasized for parents that if a child starts to develop any type of weakness to seek help at a major hospital ER immediately, even with the fear of the COVID pandemic. Abnormalities in the images of the spinal cord in AFM are sometimes very subtle, especially in the early phase, which could pose a challenge in getting a diagnosis. Dr. Olwen Murphy from Johns Hopkins University discussed research findings and enumerated what to look for radiologically when making a diagnosis. Dr. Roberta DeBiasi from Children’s National Medical Center highlighted key aspects for differentiating AFM from other infectious causes of flaccid weakness like Guillain-Barre and Botulism.
Dr. Jessica Carpenter from Children’s National Hospital in Washington D.C. and Dr. Rebecca Riggs from The Johns Hopkins Pediatric Intensive Care Unit shared about critical management and respiratory management of AFM. More than half of those diagnosed with AFM will require support in the intensive care unit (ICU) during the acute part of the disease, especially those who have weakness of both arms, their neck or face muscles. However, most of them also are able to quickly transition out of the ICU to a general floor. Acute respiratory failure (when the lungs cannot get enough oxygen into the blood) happens in AFM mostly due to weakness of the muscles that help us breathe and treating this should always be a priority when AFM is suspected. While at present no medical therapies have been proven to be efficacious in AFM, Dr. Leslie Benson from Boston Children’s Hospital shared that all treatments we currently use are off-label and based on anecdotal experience. This also means that there is a lot of room for learning, with very exciting animal experiments currently being conducted. Dr. Cristina Sadowsky, one of the symposium organizers and Clinical Director of the International Center for Spinal Cord Injury at the Kennedy Krieger Institute, shared a key message that appropriate rehabilitation is the best treatment for individuals affected by AFM and early and sustained rehabilitative interventions, done safely under medical management, are essential in resuming mobility and independence. Nerve conduction and muscle studies (recordings of how electricity travels through a nerve and how a muscle responds) can be a very useful tool in AFM for diagnosis, both in telling us which muscles are likely to recover, and in pre-surgical evaluations before a nerve or tendon transfer. Dr. Matthew Elrick shared more about the neurophysiology of AFM. Meghan Moore, and Amy Bayliss, from the Johns Hopkins Pediatric Intensive Care Unit emphasized the need to engage parents in the rehabilitation process of their child very early on, starting from the ICU setting. We must never forget about the families, especially in the acute phase of the disease, where there is little control and a lot of anxiousness. Communication with families and understanding their situation is critical to success in the continued process of outpatient rehabilitation.
Dr. Richard Scheuermann at J. Craig Venter Institute at La Jolla, California delved into explaining more about EV-D68. Thanks to his research and that of many others, we now have clues pointing towards the idea that the virus has “evolved” in recent years and has acquired the ability to “attack” the spinal cord and cause AFM. Dr. William Jackson from the University of Maryland showed us how and what happens when EV-D68 infects our cells, and Dr. Amy Rosenfeld from Columbia University explained how EV-D68 is able to infect our nervous system. Understanding how the virus works inside our cells is the foundation for identifying potential therapeutic targets that could reduce the infectivity of the virus.
On the research front, several researchers shared their incredible work both in basic and clinical sciences. Dr. Kenneth Tyler from University of Colorado Anschutz Medical Campus has developed a mouse model of EV-D68 AFM. This has allowed his research team to successfully test the effect of different treatments like antiviral drugs, IVIG, and steroids on mice that have leg weakness because of EV-D68. Good animal models are an essential step in the development of treatments for any disease. Dr. Priya Duggal from Johns Hopkins Bloomberg School of Public Health has led a very important effort for the past 8 years in collecting samples and information from families across the country with the goal to better understand the genetics of the disease and find out if we are able to identify who might be at a higher risk of being affected. Dr. Cristina Cassetti from the National Institute of Allergy and Infectious Diseases gave us an overview of where we are with the development of a vaccine against EV-D68 that is currently in process at NIAID Vaccine Research Center. Dr. Matthew Vogt from Vanderbilt University shared with us his exciting research on immunity of AFM. Dr. Vogt reminded us that although almost every adult has been exposed to EV-D68, and therefore has developed immunity against the virus (through a “neutralizing antibody”), children in the age range in which AFM is most common do not seem to possess this immunity. He is researching the possibility of being able to protect children from the disease by giving them an immune response (an antibody) against the virus. So far, he has been able to prove this in mice and is looking forward to developing it for use in humans. Dr. David Kimberlin from the University of Alabama at Birmingham spoke about the Natural History Study of AFM, a national and international effort to learn as much about AFM as fast as we can.
Drs. Benjamin Greenberg from UTSW and Ann Yeh from The Hospital for Sick Children gave inspiring talks on the importance of harmonizing all of the incredible research efforts with the reality in our hospitals and with the families, so that we can provide safe treatments and improve the care of these children. They helped us put all the pieces together from what we learned during the talks, leaving us with a very important message: we all have to adapt to the situation, but never accept it. We all need to continue working together, including the basic scientist, the physicians, the advocacy organizations and families, to improve our knowledge and the care we give to our children.
Sarah Todd Hammer, an author, dancer, and activist, started the fourth part of the symposium on management of long-term consequences of AFM with her perspective as a person with AFM. She was initially diagnosed with TM in 2010 at the age of 8 and was later re-diagnosed with AFM. She continues to dance after her diagnosis and has written three books as well. Dr. Joyce Oleszek from University of Colorado/Children’s Hospital Colorado then presented about the management of chronic medical conditions, such as respiratory dysfunction, bladder and bowel dysfunction, and functional problems associated with AFM, including but not limited to pain, fatigue and contractures.
Medical professionals from Kennedy Krieger Institute presented key information about treatment and recovery from AFM. Dr. Michelle Melicosta and Kofi Anoh discussed respiratory health in AFM, including commonly seen respiratory issues, the goals of respiratory interventions, and their institutional experience with 19 inpatient cases of AFM. Dr. Courtney Porter discussed activity based restorative therapy and its role in treating those with AFM. This type of therapy involves functional electrical stimulation, weight bearing, locomotor training, task specific practice, and massed practice. Janet Dean added to the information about rehabilitation by discussing the difference between habilitation and rehabilitation, how to determine therapy benefits with an insurer, and strategies for maximizing a limited therapy benefit. Drs. Mahim Jain and Cristina Sadowsky, discussed that individuals with AFM develop secondary loss in bone mineral density, which can increase risk of fractures or other orthopedic consequences. While at the moment there is limited evidence on the best treatment modalities for AFM, the clinical goal of treatment is to prevent fractures and other orthopedic complications and facilitate continued recovery from time of AFM diagnosis.
Drs. Sarah Kidd and Alexandra Hess from the Centers for Disease Control and Prevention (CDC) gave CDC program updates, including preparing for a spike in cases in 2020, the activities they have conducted so far and plans for additional activities in 2020. Rebecca Whitney and GG deFiebre from SRNA discussed what SRNA has done for AFM advocacy, including our education programs, support, research, and training.
Dr. Margaret Tunney from the Kennedy Krieger Institute discussed coping and adjustment for children with AFM, and how to keep kids motivated. Dr. Lana Harder from UT Southwestern and Children’s Health gave parents tips on how to advocate for their child at school, including how to understand the law and students’ rights, the process for accessing support services, and identifying resources.
The fifth and final part of the symposium was about orthopedic and surgical treatments in AFM. Dr. Riley Bove from University of California San Francisco, both a physician and a parent of a child with AFM, started the day with a discussion about unmet needs in treatment and recovery of those with AFM. Dr. Bove explained that unmet needs start at onset, with difficulties getting a prompt diagnosis, include navigating rehabilitation trade-offs, the emotional impact, and access to ongoing therapy to continue recovery.
The rest of the day involved discussions on surgical options for AFM. Dr. Andrea Bauer from Boston Children’s Hospital discussed tendon transfers, the indications and contraindications for tendon transfers, and their potential role in AFM. Dr. Paul Sponseller from Johns Hopkins School of Medicine discussed how to manage the neck, shoulders, and spine through orthopedic strategies. Dr. Colyn Watkins from Boston Children’s Hospital Management gave a talk on joint contracture, hip subluxation and limb length inequality in AFM, with a focus on bracing and surgical options. Dr. Allan Belzberg from Johns Hopkins School of Medicine continued the discussion by addressing nerve transfers in the upper extremities, while Dr. Amy Moore from Ohio State University School of Medicine discussed nerve transfers in the lower extremities, and Dr. Dan Zlotolow from Shriners Hospitals for Children discussed nerve transfers for the phrenic nerve. Dr. Belzberg gave an overview about nerve transfers and how they work and gave examples of some cases of upper extremity nerve transfers. Dr. Moore continued the discussion by describing how she applies principles of nerve transfers in the upper extremities to the lower extremities. To close the talks, Dr. Zlotolow talked about phrenic reinnervation in AFM and the need for additional research.
As a reminder, all sessions were recorded and are available along with their transcripts.