2021 Research Updates

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.