2021 Research Updates
While 2021 continued to be a challenge for our community due to COVID-19, we continued to work on various research projects and supported the work of several research publications. We know how important research is for improving the quality of life of our community, and it remains a top commitment for us as an organization. We continue to do this work through The Pauline H. Siegel Eclipse Fund for research.
We share some of the research advances here with you.
SRNA maintains our commitment to advancing the scientific understanding of ADEM, AFM, MOGAD, NMOSD, ON, and TM to help improve diagnostic speed and accuracy. Some of this SRNA-supported research was conducted by former SRNA James T. Lubin Fellows, Drs. Kyle Blackburn and Jonathan Galli, who published three research articles in 2021.
Antibody Testing in Rare Neuroimmune Disorders
The field of autoimmune neurology is rapidly evolving, and we are still learning what the best practices are for neurological antibody testing. Dr. Blackburn and colleagues published a study looking at the frequency of overlapping and repeat antibody testing in patients at the University of Texas Southwestern Medical Center (UTSW). They also looked at how these practices informed clinical decision-making and management. They found that overlapping and repeat evaluations for suspected autoimmune and paraneoplastic disorders occurred in 15.9% of patients with testing in 2017, and that these tests did not impact clinical management and repeat testing rarely differed from initial testing. They give suggestions for future practice and argue that there needs to be development and standardization of neurological autoimmune and paraneoplastic autoantibody testing practice standards.
Dr. Galli and colleagues published a study looking at the use of cell-based and ELISA assays to detect the aquaporin-4 antibody (AQP4), which is found in those with neuromyelitis optica spectrum disorder (NMOSD). Studies have shown that cell-based assays are better than ELISA assays, but ELISA testing is still commonly ordered by physicians. They found that using the AQP4 ELISA to diagnose suspected NMOSD has the potential to come back with low positive results that are unlikely to be due to NMOSD but actually multiple sclerosis (MS). Moderate positive ELISA results were associated with NMOSD but could also be seen in other diagnoses, like MS and Lyme disease. A high positive result was consistent with NMOSD. They state that physicians, if they continue to order the AQP4 ELISA, should interpret the results with caution, especially for those who do not fit in the NMOSD criteria.
TM in US Veterans Health Administration Medical Records*
A recent study was published on the characterization of transverse myelitis (TM). The researchers (including two former SRNA James T. Lubin Fellows, Drs. Sweeney and Galli) looked at data from the Veteran Health Administration’s (VHA) electronic medical records from 1999 to 2015. This national cohort analysis provided a modern point prevalence (meaning the number of cases in a population) of TM and stressed that the diagnosis of TM continues to be challenging for providers.
The study population consisted of all patients seeking care in the VHA system, including inpatient and outpatient visits. Then all TM cases were identified by reviewing each individual patient chart to ensure they met the diagnostic criteria for an accurate TM diagnosis.
961 patients out of 12,212,061 were identified with TM, including disease-related (related to multiple sclerosis, infection, or other demyelinating diseases) and idiopathic TM. The point prevalence of this group was 7.86 cases per 100,000 people, which was higher than previously reported in other studies but was similar to the most recent county-based study in the United States. This point prevalence includes those with TM of no known cause (i.e., idiopathic) and disease-associated TM. The population of patients was 67.8% Caucasian, 18.3% African American, 3.1% Hispanic/Latino, and 2.0% Pacific Islander/Asian. Like other studies that use VHA medical records, the study population was mostly older males (90.7%) with a median age of 64.2 years.
They found that those with TM had moderate to severe deficits at the time of diagnosis. Most spinal cord lesions were in the thoracic spinal cord (42.6%), while approximately a third (35.5%) were in the cervical spinal cord, and 4.2% were in the lumbar spinal cord. The remaining TM attacks occurred in both the cervical and thoracic spinal cord. About one-quarter had lesions that were longer in length than three vertebrae. Of the patients who had MRI reports of their brain, 17.2% were reported as abnormal.
68.2% of cases were diagnosed as idiopathic TM. Among all TM cases, the most common event before their diagnosis was an infection (9.7%) or vaccination (3.3%). Multiple sclerosis was the most frequent final diagnosis (16.7%). Of the 172 patients who had abnormal brain MRIs, 50.6% were eventually diagnosed with multiple sclerosis.
Spinal fluid results were available in 424 patients. An elevated protein was found in 68.4% of cases, while around half had an elevated white blood cell count. Oligoclonal bands were found in 25.6% of patients, and more than half of those with oligoclonal bands had a final diagnosis of MS.
Among those for whom it was known whether they got acute treatments, 79.4% received an acute treatment. Corticosteroids were the most common treatment, and only 4.9% received plasma exchange. 71.7% of patients who received first-line immunotherapies such as corticosteroids, IVIg, or plasma exchange had some improvement in functional outcomes, and 22.6% were stable.
The authors note that their findings indicate a lack of adequate diagnostic testing: over half (57.6%) of cases did not include CSF testing. Only 1/3 of cases were assigned a final diagnosis other than TM. The recent discovery of autoantibodies such as AQP-4 and MOG were not able to be included in this analysis because the study period was before there was widespread availability of this testing, and it was not available at all VA centers. Also, this study was not set up to evaluate the efficacy of steroids, plasma exchange, or IVIg, so this should be looked at in future studies. However, this study does give a point prevalence using a large dataset and demonstrates the importance of prompt and accurate diagnosis at symptom onset as there is potential for intervention and prevention of disease progression.
*This was written in part by Heather Peterson, a volunteer for the Siegel Rare Neuroimmune Association.
Beyond the personal health impacts, economic impacts, and changes to our medical system, the COVID-19 pandemic has dramatically impacted basic science and clinical research efforts worldwide. The Study to Investigate the Safety of the Transplantation of Human Glial Restricted Progenitor Cells Into Subjects With Transverse Myelitis at UTSW Medical Center in Dallas was impacted in 2020 and 2021. After submitting data to ensure cell viability, we are now cleared to proceed with our planned 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. We are preparing to do the first surgery in the summer of 2022, are still screening for additional participants, and will keep the community informed about the trial’s progress.
Progress Grant for NMOSD
SRNA would like to congratulate the 2021 recipient of the Progress Grant for NMOSD, Dr. Sammita Satyanarayan. The Progress Grant funds research aimed to improve the 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, those who are Black or Asian seem to be younger at onset and have more brain symptoms or MRI abnormalities than those who are White.
The Progress Grant for NMOSD aims to help the broader NMOSD community understand how to improve the diagnosis, treatment, and quality of life of people with NMOSD. Dr. Sammita Satyanarayan is conducting research on “Assessing the impact of social disparities of health on disability and access to care in NMOSD patients.” She is a neuroimmunology fellow at the Mt. Sinai Hospital in New York City, NY. Her study is focused on evaluating how the factors of people’s lives, called social determinants of health, impact their access to care, disability, and disease process in people with NMOSD.
Some of the social determinants of health Dr. Satyanarayan is studying include education access and quality, health care access and quality, neighborhood and built environment, social and community context, and economic stability. Differences in these factors can lead to differences in the disease process, which are called disparities. A better understanding of these factors can help medical professionals address disparities while providing care to their patients.
In her research, Dr. Satyanarayan is measuring how social determinants of health affect access to care and disability. Access to care can be measured by the time between symptom onset to diagnosis, the time it takes to receive the first disease-modifying treatment, and the type of disease-modifying therapy received. Disability, on the other hand, is measured by patient reported outcomes, such as ambulation status and activities of daily living; physician reported status, such as ambulation status; standardized and validated disability scores, such as the Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk; and examination of vision and visual acuity. Dr. Satyanarayan’s study will include both prospective and retrospective data and will include data from three academic medical centers – Mt. Sinai Hospital, University of Southern California, and Massachusetts General Hospital. You can learn more about the research study by viewing Dr. Satyanarayan’s presentation at the 2021 Rare Neuroimmune Disorders Symposium (RNDS).
We look forward to learning more about health disparities in people with NMOSD from Dr. Satyanarayan’s research, and we are hopeful that it will lead to better care for those in the NMOSD community. The Progress Grant for NMOSD is made possible by a grant from Horizon Therapeutics.
SRNA James T. Lubin Fellows
In addition to some of the research described above, we remain committed to funding Fellowships to train clinician-scientists in rare neuroimmune disorders. In 2021, SRNA opened our applications for our 2023-2025 Fellowship cohort. Our Fellowship program is a crucial piece of our mission to advance research on rare neuroimmune disorders.
SRNA also continues to collect data for our patient Registry. The purpose of this registry is to help advance research about rare neuroimmune disorders, collaborate with researchers from around the world, and identify participants for clinical trials. In total, 621 people have participated in the registry.
As of May 2022, 70% of respondents were diagnosed with transverse myelitis, 10% with neuromyelitis optica spectrum disorder, 7% with MOG antibody disease, 5% with acute disseminated encephalomyelitis, 4% with acute flaccid myelitis, and 4% with another disease or have yet to receive a diagnosis.
37% were diagnosed less than one week after symptom onset, but for 32% of respondents it took longer than six weeks to be diagnosed.
83% of participants received treatment after their first acute attack. However, of those who received a first acute treatment, only 32% of participants received a second treatment that was different than the first. 80% of participants received rehabilitative therapy.
80% of participants currently have weakness or paralysis, 79% of participants currently have numbness or loss of sensation, and 62% of participants have spasticity or uncontrolled muscle spasms. 54% experience neck or back pain, 76% of participants experience neuropathic pain, and 70% of participants have bladder and/or bowel symptoms.
In response to the COVID-19 pandemic, SRNA was interested in how the pandemic impacted our community, which led us to launch our COVID-19 study. The goal of the study is to understand and learn from the SRNA member community about their experiences with COVID-19, experiences accessing care during the pandemic, and other potential social challenges (e.g., job loss, issues accessing medication or other supplies). Some of those with rare neuroimmune disorders are considered high risk for severe COVID-19 disease, are on medications that suppress the immune system, or have complex, ongoing medical needs. Understanding these issues for our community during this pandemic helped us to create relevant programming and inform the medical community about the effects of this pandemic on those with rare neuroimmune disorders. The study involved participation in an interviewer-guided survey administered over the phone using Surveymonkey. Of the 100 participants in the study, 13.7% were let go from their jobs due to the pandemic, while 54.7% were not employed before the pandemic. Half of the participants had issues accessing medical care, and 80% had visits that were shifted to virtual visits. 5.3% of respondents had a COVID-19 diagnosis, but none were hospitalized.