The Cognitive Impact of Pediatric-Onset Multiple Sclerosis: Cross-Sectional and Longitudinal Insights

Pediatric-onset Multiple Sclerosis (POMS) is an inflammatory demyelinating disease of the central nervous system (CNS). Next to physical symptoms, possible cognitive consequences of this disease have been increasingly recognized, although the literature remains scarce. This study was the first to assess cognitive impairment (CI) in a Dutch POMS cohort and aimed to examine the prevalence, course, and affected cognitive domains of CI using cross-sectional and longitudinal approaches. Neuropsychological assessments (NPAs) were performed 3-12 months after symptom onset (T1; N = 31) and again 3 years after symptom onset (T2; N = 17). NPAs encompassed a total of 14 measures, including measures from the Wechsler Intelligence Scales and additional neurocognitive measures, of which performances were compared to published age-based norms. The study hypothesized POMS patients to exhibit lower overall cognitive performance, and the proportions of patients meeting the criteria for CI,...Show morePediatric-onset Multiple Sclerosis (POMS) is an inflammatory demyelinating disease of the central nervous system (CNS). Next to physical symptoms, possible cognitive consequences of this disease have been increasingly recognized, although the literature remains scarce. This study was the first to assess cognitive impairment (CI) in a Dutch POMS cohort and aimed to examine the prevalence, course, and affected cognitive domains of CI using cross-sectional and longitudinal approaches. Neuropsychological assessments (NPAs) were performed 3-12 months after symptom onset (T1; N = 31) and again 3 years after symptom onset (T2; N = 17). NPAs encompassed a total of 14 measures, including measures from the Wechsler Intelligence Scales and additional neurocognitive measures, of which performances were compared to published age-based norms. The study hypothesized POMS patients to exhibit lower overall cognitive performance, and the proportions of patients meeting the criteria for CI, categorized as Mild Cognitive Impairment (MCI) or Severe Cognitive Impairment (SCI), to be significant at both time points, with domain-specific impairments in information processing speed (IPS), verbal abilities, attention, memory, executive functioning (EF), and visuospatial cognition. Additionally, significant overall cognitive decline and domain-specific decline were expected to occur between T1 and T2. At both time points, one-sample t-tests showed overall cognitive performances to be significantly below normative expectations (T1: t(30) = -2.69, p = .01, d = -0.48, 95% CI [-0.7, -0.1]; T2: t(16) = -2.50, p = .02, d = -0.60, 95% CI [-0.7, -0.1]). At T1, 64.5% met criteria for MCI, and 54.8% also experienced SCI, with both proportions significantly higher (p < .001) than expected according to binomial testing based on Test Proportions. At T2, 52.9% met MCI criteria, and 47.1% also met SCI criteria, again significantly above expected rates (p = .004 and p < .001, respectively), aligning with our hypothesis and possibly explained by known vulnerabilities in POMS associated with myelin disruption. Domain-specific impairments were observed in measures of attention (t(30) = -4.12, p < .001, d = -0.47, 95% CI [-2.2, -0.7]) and IPS (t(30) = -3.3, p = .003, d = -0.59, 95% CI [-1.3, -0.3]) at T1, but only IPS (t(16) = -3.41, p = .004, d = -0.83, 95% CI [-1.3, -0.3]) showed significant at T2, only partly aligning with our hypothesis. Contrary to our expectations, a repeated-measures MANOVA showed no significant overall cognitive decline over the 2.5-year interval (Wilks’ Λ = .39, F(6, 9) = 2.40, p = .12, η² = .62), although there was a univariate decline in verbal abilities (F(1, 14) = 10.84, p = .005, η² = .44). However, this finding should be interpreted with caution due to the absence of a multivariate effect and the small sample size. These findings underscore that CI is common and persistent in POMS, particularly affecting attention and IPS, although no group-level decline was observed. These findings underscore the need for targeted cognitive interventions and emphasize the importance of conducting further research using standardized, comprehensive assessment batteries.Show less

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The Cognitive Impact of Pediatric-Onset Multiple Sclerosis: Cross-Sectional and Longitudinal Insights