Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases

Original Publication: Lotan I, Romanow G, Levy M. Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases. Mult Scler Relat Disord. 2021 Oct;55:103189. doi:

In response to the COVID-19 pandemic, several vaccines were developed and distributed across the world. Some of these vaccines received FDA approval in the United States (Pfizer, Moderna, and Johnson & Johnson), and another vaccine was approved by the European Union (AstraZeneca). These vaccines were recommended by several expert committees for people with autoimmune diseases and for people who are immunocompromised; however, the clinical trials excluded most people with rare neuroimmune disorders, which was cause for uncertainty among many people with one of these disorders and physicians.

Researchers Dr. Michael Levy, Dr. Itay Lotan, and Gabriela Romanow conducted an anonymous survey to report real-world safety data of the COVID-19 vaccine in persons with rare neuroimmune disorders. Participants were recruited from a closed Facebook group called “The NMO Clinic”. Of the 438 respondents, 55.3% had a diagnosis of neuromyelitis optica spectrum disorder (NMOSD), 22.6% had MOG antibody disease (MOGAD), 18% had transverse myelitis (TM), 2.5% had recurrent optic neuritis, 1.4% had acute disseminated encephalomyelitis (ADEM), and 0.3% had isolated optic neuritis. 27.4% of participants had associated comorbidities, and 80.1% of participants were being treated with immunotherapies, the most common of which was Rituximab.

Participants were asked whether they experienced immediate adverse events, like injection reactions, fever, or chills, following vaccination. 31.5% of respondents reported immediate adverse events, the most common of which were reactions at the injection site, including pain, redness, and swelling, followed by headache, muscle pain, fatigue, fever, chills, and dizziness. Of those who reported immediate adverse events, the majority were less than 55 years old. Of the participants who were being treated with immunotherapies, 35.3% reported immediate adverse events, in comparison to 32.1% of participants who were not being treated with immunotherapies, and this difference was not statistically significant. 51.4% of the participants on immunotherapies were on B-cell depleting agents including rituximab, ocrelizumab, and inebilizumab, and 33.5% of these participants experienced immediate adverse reactions. Comparatively, 67.5% of participants receiving other immunotherapies reported immediate adverse reactions.

Participants were also asked whether they experienced new or worsening neurological symptoms following vaccination. 16.7% of participants reported new or worsening neurological symptoms after receiving the COVID-19 vaccine. Of these, the majority were women (80.8%) and were being treated with immunotherapies (72.6%). The most common neurological symptoms were sensory disturbances such as numbness, tingling, and itching sensations; increased pain; muscle weakness; gait instability; visual symptoms; and sphincteric problems. Of participants who experienced new or worsening neurological symptoms, 82.2% did not require any additional treatment, while 12.4% received corticosteroids (1 in conjunction with IVIG), 4.2% were treated with additional painkillers, and 1.4% were treated with anti-nausea medication. The majority (52.1%) of respondents with new or worsening neurological symptoms reported that their symptoms resolved within 1-3 days. No participants reported having an MRI-confirmed relapse following vaccination.

The researchers compared the safety data from Pfizer’s clinical study of the COVID-19 vaccine in the general population and found that the rate of adverse events was higher in the general population than in the rare neuroimmune population who participated in this study. A possible explanation for this is that the majority of participants in this study were being treated with immunotherapies, which may blunt the effect of the vaccine, in turn causing less severe adverse events. This was especially prevalent in participants who were being treated with B-cell depleting therapies such as Rituximab. This observation should be evaluated in further studies.

The low rate of new or worsening neurological symptoms following COVID-19 vaccination is similar to data from existing (non-live-attenuated) vaccines that were not associated with a higher risk of relapse in autoimmune diseases. The researchers note that data reported in this study may help to alleviate hesitancy in the rare neuroimmune population to receive the COVID-19 vaccine.

A limitation of this study was that the data were reported anonymously and could not be confirmed by reviewing medical records. Also, participants did not undergo a medical examination to evaluate their symptoms, and all data were patient-reported. Finally, the study may not be representative of the rare neuroimmune population as a whole, because factors such as socioeconomic status, ethnic background, and physical disability can affect access to social media and internet; however, characteristics such as majority female, age, and immunotherapy treatments are similar to other groups of participants of NMOSD studies that have been published.

The researchers conclude that the safety of COVID-19 vaccines in the rare neuroimmune disorder community seems favorable. The rate of adverse events following vaccination is similar to that of the general population, and the rate of new or worsening neurological symptoms is relatively low with most symptoms being mild, resolving quickly, and not requiring additional treatment. The data should be evaluated in further studies.

Pediatric NMOSD Observational Study Opportunity

A Pediatric NMOSD Observational Study opportunity is open for enrollment to any pediatric patient, age 2 to 17 years, that has tested positive for the AQP4 antibody, regardless of their location. The study, led by Dr. Sean Pittock of Mayo Clinic along with Alexion Pharmaceuticals, is being done to collect information to develop a database on the natural history of NMOSD in pediatric patients who test positive for AQP4-IgG.

The lack of information on the course and natural history of NMOSD in children is a limiting factor in performing drug studies for children with this disorder. Participation in the study will allow for the collection of clinical information over a one-year period to help inform on the natural history of NMOSD and to build a repository of pediatric patients. A repository or database of information will allow the rare disease community, and medical and scientific researchers, to increase knowledge of NMOSD. It will also identify appropriate individuals for specific drug studies and may also help serve as a control group for future research.

This is an observational, prospective study, and information (e.g., baseline data, self-report assessments, etc.) is collected over the course of one year: at enrollment, 3 months, 6 months, 9 months, and 12 months (+/- 1 month for each time point). Travel to Mayo Clinic is not necessary for participation!

A full description of data collected, self-reporting assessments used, and timepoints for data collection can be found here.

Inclusion Criteria include the following:

  1. AQP4 positive.
  2. Ability to give informed consent by patient or caregiver.

Exclusion Criteria:

Inability to complete required forms via phone, mail, or email.

If you or your child have questions or are interested in participating, please contact Cara L Thomas, AA, at 507-722-5563, or via email [email protected], or Katie Dunlay, BA, at 507-538-5418, or via email at [email protected].

It is through your active consideration and participation in research that assists our medical and scientific community with identifying and carrying out research priorities for our children diagnosed with NMOSD. Thank you for your thoughtful consideration!

Visit the study informational page on SRNA.

Visit the study informational page on

Patient Attitudes Toward NMOSD

By Sheryl Lapidus, Senior Director of Patient Advocacy, HORIZON Therapeutics

What can the experiences of those with NMOSD tell us?

Today, there are over 7,000 known rare diseases, creating a vast community of individuals connected by a common thread. However, each of these individuals is on their own journey, with unique experiences and support systems. This is very much the case for those with neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disorder that causes recurrent inflammatory attacks of the optic nerve, spinal cord and brain. Throughout my time as a patient advocate, I’ve had the opportunity to talk with numerous individuals living with NMOSD who have expressed the frustration and confusion that come from living with a rare disease. From misdiagnosis to navigating education and resources to the struggles of finding the best treatment option, the NMOSD journey is a complicated one that must be better understood in order to ensure that we are doing all that we can to improve the lives of those who are living with this disease and their families.

With that goal in mind, myself and a team of NMOSD researchers from the Instituto Nacional de Neurología y Neurocirugía, Massachusetts General Hospital and Harvard Medical School set out on our own journey to understand the experiences and feelings of those living with NMOSD. We began this exploration by surveying 151 participants, asking them questions on a wide range of topics including symptoms, diagnosis and, more importantly, how individuals felt throughout the course of their NMOSD. Survey responses were representative from people of all ages (<10 to >70 years), ethnicities (86% not Hispanic/Latinx, 8% Hispanic/Latinx, 6% NA), education levels and genders (83% female, 12% male, 5% other). Their backgrounds and responses demonstrated how diverse this community is and helped to set us on the path of determining the common challenges and victories these individuals face every day.

As diverse and unique as everyone’s experience with NMOSD is, common triumphs and struggles became apparent from the survey results. Around initial diagnosis, many of those surveyed felt scared (57%), frustrated (40%) and bewildered (37%). These emotions occur among many people with NMOSD because they may have previously been misdiagnosed and continued to feel an uncertainty with how their lives would unfold following diagnosis. One survey participant shared how their struggles made them feel, stating: “It was hard being diagnosed. I was a month and a half away from getting married. I had always been healthy up until I wasn’t. I had no real medical history. I was so scared of what the future would hold.”

For those with NMOSD, the survey results showed that the journey doesn’t stop at diagnosis, but it does mark an important milestone on the road to improving their daily lives. One of the pivotal moments, according to the survey results, was the transition from a general physician to an NMOSD specialist, with 77% of the respondents feeling relieved after meeting with their specialist. This turning point is not only an important step in improving the physical health of those living with NMOSD, but also their mental and emotional health.

As I look back on these survey responses, it’s clear that a lot of progress has been made in supporting the NMOSD community. As a patient advocate, I’ve seen the great efforts to further NMOSD education among health care professionals, the NMOSD community and the public with the SRNA podcast series, ABCs of NMOSD, and the Let’s NMOwn the Path Forward community, to name a few examples. The community’s efforts, resource centers and social media platforms have already allowed many to find a new way to connect, feel less alone and reduce the uncertainty around what NMOSD means for their future. As we raise awareness of this rare disease, we aim to close the gap between a person’s initial symptoms and their diagnosis, allowing for earlier identification of disease and quicker access to treatments, but more can still be done. That’s why our team at Horizon Therapeutics is working diligently to improve the lives of those with NMOSD every day by going beyond science to work with the community. The path to improving the lives of those with NMOSD is a complicated one, but to follow the words of one of the survey respondents, “I am trying my best every day,” so we will continue to do our best, too, to support the NMOSD community.

Sheryl Lapidus is Senior Director of Patient Advocacy at HORIZON Therapeutics. She is responsible for building partnerships with US and international patient advocacy organizations that support individuals living with NMOSD and other rare disease focused patient advocacy groups.

Prior to joining HORIZON, Sheryl spent more than thirty years focused on the oncology and hematology specialty area. Her experience includes field sales, account management, corporate affairs, and patient advocacy. Sheryl most recently served as Senior Director of Patient Engagement at Viela Bio where she was responsible for establishing the patient engagement department.

Sheryl holds a Bachelor of Arts degree in psychology from the California State University at Northridge and a Master of Arts degree in gerontology from the University of Southern California. She currently lives in Washington, DC. Her hobbies include travel, spending time with her three adult children and her two golden retrievers.

Apply to SRNA’s Progress Grant for NMOSD

The Siegel Rare Neuroimmune Association’s Eclipse Fund for research is excited to share the establishment of The Progress Grant for NMOSD, made possible by a research grant from Horizon Therapeutics.


The Eclipse Fund in memory of Pauline H. Siegel was established to support and accelerate research that will directly impact quality of life for the members of our community.

The aim of this grant is to fund research aimed to improve understanding of neuromyelitis optica spectrum disorder (NMOSD), focused on specifically Asian and African American populations. In studies on NMOSD, we see that this disorder disproportionately affects those who are Black or Asian, unlike MS, which is more common among those who are White. Also, Black and Asian patients seem to be younger at onset and have more brain symptoms or MRI abnormalities than White patients.

The purpose of the Progress Grant for NMOSD is to help the broader NMOSD community understand how to improve diagnosis, treatment and quality of life of people with NMOSD. Research projects may focus on access to care, mental and psychosocial aspects of living with NMOSD, clinical differences, improving diagnosis and clinical care, therapeutics, or basic science projects.


The Progress Grant for NMOSD will award one $25,000 grant award to conduct original research. All funds will be used to support the research directly. SRNA does not support indirect institutional costs.


Grants are made to organizations on behalf of a named Principal Investigator. Applicants must provide a research project consistent with the goals of the award that helps advance the field forward.

Application Dates:

Open Date – April 5, 2021
Closing Date – June 30, 2021
Review and Board approval – July-August 2021
Awards announced – September 2021

Application Process:

Proposals submitted through the online form should provide a detailed description of the research or clinical project that will be partially or fully supported by the grant and a budget providing details of the estimated costs. Proposals are reviewed by our basic and clinical scientists and experts on SRNA’s Medical and Scientific Council. Additional expertise may be sought from ad-hoc reviewers to ensure comprehensive scientific review. Applications will be reviewed based on innovation, scientific rigor and alignment with the goals of the grant. Potential conflicts of interest for reviewers and applicants must be mentioned in the application and declared prior to the review and will be recused from the review process.

Recommendations for funding are made to the Board of Directors of SRNA. The final approval for funding is provided by the Board.

Additional Guidelines:

Funding from SRNA may not be used to cover any indirect costs.

Publications and Reporting Requirements:

As reporting requirements, SRNA would require two articles (as six-month reports) for SRNA’s Magazine, which describe the progress and findings from the research. We also require a final report be submitted detailing the expenditure of the funds and a short summary that we will publish on the SRNA website. SRNA should be acknowledged in any publications of research results that were supported by the grant.

Public Access Policy:

The Siegel Rare Neuroimmune Association funds clinical and biomedical research in order to better understand the causes of Acute Disseminated Encephalomyelitis, Acute Flaccid Myelitis, MOG Antibody Disease, Neuromyelitis Optica Spectrum Disorder, Optic Neuritis, and Transverse Myelitis; and to advance early diagnosis, treatment, and cures. The main output of this research is new knowledge. To ensure this knowledge can be accessed, read, applied, and built upon in fulfillment of our goals, the Siegel Rare Neuroimmune Association expects its researchers to publish their findings in peer-reviewed journals.

In addition, it is a condition of the Siegel Rare Neuroimmune Association’s funding that a copy of all funded research outputs, in the form of final, peer-reviewed manuscripts, must be delivered to the Siegel Rare Neuroimmune Association upon acceptance.  These manuscripts will be made publicly available on the Siegel Rare Neuroimmune Association website no later than 12 months after the official date of publication.

This requirement applies to all Siegel Rare Neuroimmune Association grants awarded after January 1, 2012.

The policy is developed with the Scholarly Publishing and Academic Resources Coalition (SPARC) and is based on the policy developed by Autism Speaks, with that organization’s permission.


Please click here to apply.

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].