Susan Jeffrey

September 11, 2014

BOSTON — A new study suggests no cognitive disadvantage in the long term for patients with multiple sclerosis (MS) that began in childhood vs those with adult-onset disease.

Researchers are reporting that overall, cognitive outcomes were similar between the groups and that there were actually fewer patients in the pediatric-onset group, matched with adult-onset patients for age and education, who were classified as cognitively impaired. However, the difference between groups was not statistically significant.

"Since disease onset in a period of active brain growth and maturation may render pediatric-onset subjects more vulnerable to cognitive issues, our findings suggest good compensatory/recovery abilities in these subjects, possibly related with enhanced brain plasticity in early life," the researchers, with lead author Bahia Hakiki, from the University of Florence, Italy, concluded.

Dr. Hakiki presented their findings here at MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS).

Brain Plasticity

Pediatric-onset MS represents 3% to 5% of the overall MS population and "poses unique diagnostic and therapeutic challenges," she noted. Compared with patients developing adult-onset disease, pediatric patients have relapsing-remitting disease course at onset in more than 90% of cases, have higher clinical and MRI disease activity, and have a slower rate of disability accumulation, although disability is still seen at a younger age.

Cognitive issues are "particularly relevant" in this population, she added, because disease occurs during key periods of brain growth, active primary myelination, maturation of neural networks, and key academic training years. "But on the other hand, brain plasticity and recovery may be more efficient in this group," Dr. Hakiki said. "For this reason, final outcome of cognitive performance can be evaluated only in the long term."

Previous studies suggest a prevalence of cognitive impairment in pediatric-onset disease of 30% to 50%, with a neuropsychological pattern similar to that seen in adult-onset MS, including particular involvement of attention, information-processing speed, learning and memory, executive function, and visuospatial abilities, she noted. "Moreover, it has some peculiar aspects of cognitive impairment," she said, with involvement of linguistic skills, which is spared in adult-onset MS, and sometimes an effect on genera intelligence.

The aim of this study, then, was to determine whether the cognitive effects in adulthood are worse among pediatric-onset vs adult-onset cases and, if so, to what extent. They also looked to see whether they could identify any predictors of compensatory abilities in the pediatric-onset patients.

To do this, they compared cognitive performance between 2 groups of adults with MS: 1 that had pediatric-onset disease and 1 with adult-onset disease. Patients were matched for age, education, relapsing-remitting disease course, and scores on the Expanded Disability Status Scale. Patients with a history of conditions that would be expected to interfere with cognition, such as head trauma, learning disability, or drug and alcohol abuse were excluded.

All participants underwent neuropsychological assessment using Rao's Brief Repeatable Battery (which assesses learning memory, visuospatial abilities, attention and information-processing speed, and verbal fluency) and the Stroop test (which gauges executive function). Depression was also assessed by using the Montgomery-Asberg Depression Rating Scale and fatigue by using the Fatigue Severity Scale. Significant cognitive impairment was defined as failure on more than 2 cognitive tests.

Ongoing analyses include basal IQ, assessment of leisure activities, and parental education, Dr. Hakiki noted, which should allow the investigators to estimate cognitive reserve in the participants.

In addition to cognitive testing, conventional MRI was done, assessing T1 and T2 lesion volume as well as brain volume, white matter volume, and cortical volume. Resting-state functional MRI is ongoing in these groups.

For this analysis, the authors compared 30 adult-onset patients (9 men and 21 women) with 14 pediatric-onset patients (8 men and 6 women), with an average age of 25 and 27 years, respectively. As expected, the duration of disease was longer in the pediatric-onset patients than the adult-onset patients: 9.8 years vs 3.7 years. They were well matched in terms of EDSS scores, disease course, and use of disease-modifying therapies, she noted.

Less Cognitive Impairment

No difference was found between the groups in terms of mean scores on the neuropsychological tests or in the number of tests failed, Dr. Hakiki reported. Interestingly, more patients in the adult-onset group than the pediatric-onset group met criteria for cognitive impairment: 27% vs 14%. No differences were found in measures of fatigue or depression.

The cognitive profile across tests was similar between the 2 groups, she said, "showing a prominent involvement of tests exploring information processing speed, followed by tests exploring executive function and memory."

In a subset of 22 patients who underwent MRI (11 pediatric and 11 adult-onset patients), the pediatric-onset patients showed a nonsignificant trend toward higher white-matter lesion load, but no differences were seen between the groups in terms of brain volumes.

"The comparable brain volumes, despite a longer disease duration and tendency to accumulate more lesions, may suggest a greater repair capability in these patients," Dr. Hakiki concluded.

Going forward, they hope to extend the study sample, complete the assessments of cognitive reserve as well as MRI analysis, and then integrate the cognitive and MRI data, she said.

Brenda L. Banwell, MD, chief of neurology at the Children's Hospital of Philadelphia, Pennsylvania, who comoderated the Young Investigators session where these results were presented, pointed out that the age at onset for the pediatric-onset patients was 15.6 ± 2.1 years.

"The resiliency to cognitive impairment may be very different of course in patients who start much younger," Dr. Banwell said. "Obviously you can't address that in this cohort, and you only had 14% cognitive impairment, which is what about half of studies that included younger kids have shown. Are you going to repeat this now with younger-onset patients?"

Dr. Hakiki noted they are planning to include younger-onset patients in the extended study sample to address this question.

Dr. Banwell told Medscape Medical News that both groups were relatively intact even though the pediatric-onset patients had a longer disease duration.

"The low proportion of impaired patients limits the ability to correlate with imaging," she noted. "Further work in a larger group whose MS onset occurred at a younger age — especially prepuberty — would be of great value."

 

MS Boston 2014: 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS). Abstract YI2.3. Presented September 10, 2014.

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