Faculty Bibliography

BACKGROUND: Pediatric multiple sclerosis (MS) represents approximately 5% of the MS population; information regarding clinical features is slowly accumulating. Cognitive and psychiatric impairments frequently occur, but remain poorly understood. OBJECTIVES: To describe psychiatric diagnoses among children with MS referred for psychiatric assessment and their relation to cognitive impairment. METHODS: Forty-five pediatric MS patients (aged 8 to 17 years) were referred for outpatient psychiatric evaluation including a psychiatric interview (K-SADS), a clinician-based global assessment of functioning (Children's Global Assessment Scale, CGAS), a neurologic examination including the Expanded Disability Status Scale (EDSS), and a neuropsychological test battery. RESULTS: The most common categories of psychiatric diagnoses were anxiety disorders (n=15), attention deficit hyperactivity disorder (ADHD, n=12), and mood disorders (n=11). Cognitive impairment was classified in 20/25 (80%) of patients meeting criteria for a psychiatric disorder versus 11/20 (55%) of those without psychiatric disorder (p=0.08). Those diagnosed with anxiety or mood disorder had the highest frequency of cognitive impairment, with a significantly higher rate when compared with those with psychiatric diagnoses in other categories (p=0.05). CONCLUSIONS: A variety of psychiatric diagnoses can occur in children with pediatric MS. Many of these children also had cognitive impairment, particularly those in the mood and anxiety groups.

BACKGROUND: Approximately one-third of those with pediatric-onset multiple sclerosis (MS) experience cognitive impairment. Less is known concerning their change in cognitive functioning over time. OBJECTIVE: Changes in cognitive function over time were measured in the largest pediatric cohort to date through the US Network of Pediatric MS Centers. METHODS: A total of 67 individuals with pediatric MS (n=62) or clinically isolated syndrome (CIS, n=5), ranging from 8-17 years of age (mean age +/- standard deviation (SD)=14.37 +/- 2.02) completed initial and follow-up neuropsychological testing after an average of 1.64 +/- 0.63 years apart. The nine tests administered measure general intellect, attention and working memory, verbal memory, visuomotor integration, language, and executive functioning. RESULTS: Rate of impairment (having one-third or more scores in the impaired range) was 37% at baseline and 33% at follow-up. Tests commonly impaired were measures of visuomotor integration, speeded processing, and attention. Most tested did not decline over two years. There was no clear pattern of change on any specific measure. CONCLUSION: Findings suggest that, over short timeframes, stable or even improved performances on measures of cognitive ability can occur. Pediatric MS may instead prevent expected age-related cognitive gains.

BACKGROUND: Pediatric-onset multiple sclerosis (MS) patients represent a subpopulation who are diagnosed during the course of development. Social cognitive deficits have recently been recognized in adults with MS. It is critical to identify whether these youngest patients with the disorder are also at risk. OBJECTIVE: To determine whether pediatric-onset MS is associated with social cognitive deficits. METHODS: Consecutively-recruited participants with pediatric-onset MS were compared to a group of age- and gender-matched healthy controls on Theory of Mind (ToM) task performance. Tasks measured facial affect recognition (Reading the Mind in the Eyes Test), detecting social faux pas (Faux Pas Test), and understanding the perspective of another (False Beliefs Task). RESULTS: Twenty-eight (28) pediatric-onset MS participants (median age 17 years) and 32 healthy controls (median age 16 years) completed the study. The MS participants performed worse than controls on all three ToM tasks: Reading the Mind in the Eyes Test (p = 0.008), the Faux Pas Test (p = 0.009), and the False Beliefs Task (p = 0.06). While more MS than control participants were impaired on a measure of information processing speed (the Symbol Digit Modalities Test; 38% versus 6%), it did not account for the differences in ToM performance. CONCLUSIONS: Social cognition may represent an area of cognitive functioning affected by MS in the pediatric-onset population. These processes are especially important to study in younger patients as they may have long range implications for social adjustment, employment, and well-being.

OBJECTIVE: To evaluate the Symbol Digit Modalities Test (SDMT) as a tool for identifying pediatric-onset MS patients at risk for cognitive impairment. BACKGROUND: The SDMT is a brief measure of cognitive processing speed that is often used in adult MS patients. Approximately one-third of pediatric-onset MS patients have cognitive impairment and there is a need for an effective screening instrument. DESIGN/METHODS: Seventy (70) consecutive outpatients with pediatric-onset MS underwent clinical evaluations including the SDMT and were compared to those with other pediatric neurological diagnoses (OND, n=40) and healthy controls (HC, n=32). A subset of the MS group and all healthy controls completed neuropsychological evaluation within one year of SDMT administration. RESULTS: The MS group performed worse on the SDMT compared to the HC group (p=0.02). Thirty-seven percent (37%) of the MS, 20% of the OND, and 9% of HC groups scored in the impaired range. For MS participants who underwent neuropsychological testing (n=31), the SDMT showed 77% sensitivity and 81% specificity for detecting neuropsychological impairment when administered within one year and reached 100% sensitivity when the interval was under two months (n=17). Overall, older age and increased disability predicted poorer SDMT performance (age r=-0.26, p=0.03) and the Expanded Disability Status Scale score or EDSS (r=-0.47, p<0.001), while a history of optic neuritis predicted better performance (p=0.04). Optical coherence tomography measures were not related to SDMT performance. CONCLUSION: In this preliminary study, the SDMT was an effective brief screen for detecting cognitive impairment in pediatric-onset MS.

BACKGROUND: Pediatric multiple sclerosis (MS) is a rare disorder with significant consequences. Quantitative MRI measurements may provide significant insights, however multicenter collaborative studies are needed given the small numbers of subjects. The goal of this study is to demonstrate feasibility and evaluate lesion volume (LV) characteristics in a multicenter cohort of children with MS. METHODS: A common MRI-scanning guideline was implemented at six member sites of the U.S. Network of Pediatric MS Centers of Excellence. We included in this study the first ten scans performed at each site on patients meeting the following inclusion criteria: pediatric RRMS within 3 years of disease onset, examination within 1 month of MRI and no steroids 1 month prior to MRI. We quantified T2 number, T2-LV and individual lesion size in a total of 53 MRIs passing quality control procedures and assessed gadolinium-enhancing lesion number and LV in 55 scans. We studied MRI measures according to demographic features including age, race, ethnicity and disability scores, controlling for disease duration and treatment duration using negative binomial regression and linear regression. RESULTS: The mean number of T2 lesions was 24.30 +/- 19.68 (range:1-113) and mean gadolinium-enhancing lesion count was 1.85 +/- 5.84, (range:0-32). Individual lesion size ranged from 14.31 to 55750.60 mm3. Non-white subjects had higher T2-LV (unadjusted pT2-LV = 0.028; adjusted pT2-LV = 0.044), and maximal individual T2-LV (unadjusted pMax = 0.007; adjusted pMax = 0.011) than white patients. We also found a trend toward larger mean lesion size in males than females (p = 0.07). CONCLUSION: Assessment of MRI lesion LV characteristics is feasible in a multicenter cohort of children with MS.