Results Summary
What was the research about?
Transverse myelitis, or TM, is a rare disease that causes inflammation of part of the spinal cord. TM can cause pain, numbness, muscle weakness, paralysis, and problems with bladder and bowel control. Because TM is a rare disease, few studies have looked at how well treatments for TM work.
In this study, the research team looked at whether a treatment called plasma exchange, or PLEX, helped improve physical function in children with TM. PLEX filters certain proteins out of a person’s blood and replaces the proteins with man-made protein or with plasma from a donor. The team wanted to compare children with TM who received PLEX with children who didn’t receive it.
What were the results?
Fewer children with TM joined the study than planned. As a result, the study couldn’t compare children with TM who received PLEX with children who didn’t receive it.
Among children with TM in the study, 11 received PLEX. In eight of these children, PLEX followed another treatment. Four had improved physical function one year after treatment. Three children with TM had PLEX alone. All three children had improved physical function one year after treatment.
During the study, the research team found a new type of TM called acute flaccid myelitis, or AFM. The original type of TM and AFM differ. As a result, the study looked at the children with TM and AFM separately. The study found that PLEX may help some children with AFM. But given the small number of children with AFM who received treatment, these findings aren’t certain.
Who was in the study?
The study included 39 children with TM and 51 children with AFM ages 0–18 who were diagnosed between 2014 and 2018. To take part in the study, children had to be diagnosed in the previous six months. Of the children, 79 percent were white, 6 percent were African American, 6 percent were Asian, 6 percent indicated more than one race, and 4 percent didn’t report race; 17 percent were Hispanic or Latino. The average age at diagnosis was 7, and 60 percent were boys.
What did the research team do?
The research team worked with a patient advocacy group called the Transverse Myelitis Association to recruit children with TM. The association recruited children online and from seven hospitals that treat TM in the United States.
The research team reviewed health records to see whether children received PLEX. At 6 and 12 months after the study began, doctors looked at physical function in children who were recruited from hospitals.
Adult patients with TM, families of children with TM, and the Transverse Myelitis Association helped design the study.
What were the limits of the study?
Fewer patients joined the study than planned. Also, the study couldn’t look at data for children with TM and AFM together. As a result, the study had too few children to compare treatments.
Future research could continue to look at treatments for TM and AFM.
How can people use the results?
Researchers can use the results when planning studies for children with TM and AFM.
Professional Abstract
Objective
To determine whether plasma exchange (PLEX) improves physical function in children with transverse myelitis (TM)
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | 90 children ages 0–18 who were diagnosed with TM within the previous 6 months, of whom 51 had a new variant of TM called AFM |
| Interventions/ Comparators |
|
| Outcomes |
Primary: clinician-assessed physical function score Secondary: family-reported ratings of children’s mobility and upper extremity function |
| Timeframe | 1-year follow-up for primary outcome |
This prospective observational cohort study examined the effect of PLEX versus other treatments on physical function, mobility, and upper extremity function in children with TM.
The study included 90 children with TM diagnosed between 2014 and 2018. The Transverse Myelitis Association referred patients ages 0–18 who had a diagnosis of TM within the previous six months to the research team. Referrals included an in-person cohort of children from seven hospitals across the United States and an online cohort of children not assessed in person during the study. Of the children, 79% were white, 6% were African American, 6% were Asian, 6% indicated more than one race, and 4% did not report race; 17% were Hispanic or Latino. The average age at diagnosis was 7, and 60% were male.
The research team reviewed medical records to determine whether children received PLEX when they first experienced symptoms of TM. At 6 and 12 months after study enrollment, clinicians assessed physical function scores for the in-person cohort, and the research team assessed scores from patient medical records for the online cohort. At the same time points, families of patients in both cohorts reported their ratings of mobility and upper extremity function in online surveys.
Adult patients with TM, families of children with TM, and the Transverse Myelitis Association helped create the study protocol.
Results
The study could not compare outcomes between children who received PLEX versus other treatments due to under-recruitment and missing follow-up data.
Only 11 children with TM in the study received PLEX. Three patients with TM who received PLEX had complete study data one year after symptoms. All three achieved a clinically significant increase in physical function. Eight patients received intravenous immunoglobulin (IVIG) as their first-line therapy at onset, followed by PLEX. Of these patients, four achieved a minimum clinically significant increase in physical function at one year.
During the study, an unexpected outbreak of a new variant of TM called acute flaccid myelitis (AFM) occurred. To account for potential differences between these two clinically and pathologically distinct TM subtypes, the study examined these populations separately. Exploratory analyses for patients with AFM did not show differences in physical function based on treatment type, but these results are not conclusive. Trends in the data support the effectiveness of using anti-inflammatory therapies in some children.
Limitations
This study had several significant limitations, including under-recruitment, missing follow-up data, and the emergence of a clinically and epidemiologically significant subtype of an already rare condition. These limitations prevented the research team from completing the planned primary analysis.
Conclusions and Relevance
Based on lower than expected recruitment and identification of the new TM variant, the study was not powered to determine statistically significant differences in treatment outcomes. In this small study, children with TM experienced some level of recovery after treatment.
Future Research Needs
Future studies could continue to examine treatments for TM using a larger sample size.
Final Research Report
View this project's final research report.
Journal Citations
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers noted that the original goals of this study, comparing different treatments for transverse myelitis (TM), could not be accomplished as planned because the researchers could not meet recruitment goals. However, the study did provide important information about a related disease, acute flaccid myelitis (AFM), that saw a surge in diagnoses during the study. The reviewers accepted the change in the study’s goal, from comparing treatments for TM to comparing AFM to two types of TM. The reviewers’ comments primarily asked the researchers to clarify how they conducted their analyses. The researchers also simplified some of the descriptions of diagnostic similarities and differences between AFM and TM.