Meaningful Cognitive Gains in Pediatric MS Captured Using Pencil-Paper Test

A computer-based training program that exercises distinct components of attention and working memory can improve cognition in young people with pediatric-onset multiple sclerosis (POMS), a new study indicates.

Findings also support a common pencil-and-paper measure of cognition, called the Symbol Digit Modalities Test (SDMT), in detecting clinically meaningful changes in thinking abilities and concentration among these children.

This finding was particularly important because SDMT is widely used in clinical care of adult and pediatric patients “due to its short duration and ease of administration, [and] high sensitivity in detecting subtle changes in cognitive functioning in MS,” and is increasingly part of clinical trials in this disease, the researchers wrote.

Their study, “A Randomized Computer-Assisted Rehabilitation Trial of Attention in Pediatric Multiple Sclerosis: A Post Hoc Analysis,” was published in Brain Sciences.

Cognitive deficits are common to POMS patients; between 30% and 50% of all children with POMS experience at least mild cognitive impairment. In caring for these young people, and in conducting clinical trials of investigational treatments, it is useful to have standardized measurements that assess cognitive abilities.

One such tool is the SDMT. In this relatively simple assessment, a person substitutes digits for abstract symbols using a reference key. Performance is affected by a person’s ability to hold sustained attention, as well as working memory and cognitive flexibility.

Prior research has indicated that a change of at least four points on the SDMT is clinically significant (that is, reflective of changes that would be noticeable to an individual in their day-to-day life) in adults with MS. However, whether this same cut-off for clinical significance is applicable to children with POMS is unclear.

Scientists at the University of Bari in Italy conducted a post hoc analysis of clinical trial data, meaning an analysis undertaken after the trial is finished and all data collected.

The team used data from a randomized clinical trial that enrolled 16 children with POMS. Half underwent specific training that generally consisted of exercises aiming to improve cognitive abilities, done at the home in two one-hour sessions each week for three months. The other half undertook non-specific training.

Before and after the three months of training, the participants underwent a battery of cognitive tests, including the SDMT.

Previously reported trial findings showed that children in the specific training group had significant improvements in cognition, as assessed using the Cognitive Impaired Index (CII) test. In this post hoc analysis, the researchers examined whether any of the trial’s participants achieved a clinically significant four-point improvement in SDMT scores.

All eight children given the three months of training showed a clinically significant four-point improvement in SDMT. Among the eight children without this training, in contrast, two showed clinically significant SDMT improvements, two experienced clinically significant worsening, and the remaining four had no clinically significant change.

“In this post hoc analysis of a randomized trial, we showed, for the first time in a pediatric cohort, that an increase of at least four points in the SDMT could also indicate a clinically meaningful improvement” in cognitive skills, the researchers concluded.

“This is based on the observation that all the patients with an increase in the SDMT score of at least four points also reported an improvement in their overall cognitive functioning as measured by the CII,” they added.

Limitations of the trial, according to the researchers, include its relatively small size, and the fact that it was conducted at a single center, so it’s unclear whether the results are generalizable to everyone with POMS. They also noted that other assessments of real-world cognitive abilities — such as school performance — were not analyzed.

“Further studies on larger populations are needed to confirm the clinical validity of [the four-point cut-off for clinical significance on the SDMT] and its applicability in the routine clinical practice setting,” the researchers wrote.