Faculty Bibliography

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.

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) 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: Fatigue is the most commonly reported symptom in multiple sclerosis (MS). Purpose: This brief narrative review addresses the clinical features, pathophysiology, and management of MS fatigue, as well as the varied approaches to its definition and measurement. Methods: A literature search was conducted through Medline of studies published since 1984, with a focus on findings reported since 2008. Results: Studies of MS fatigue have primarily relied on the definition of fatigue as a subjective sense of tiredness measured through self-report. Additional studies have measured fatigability in MS, as demonstrated by a decline in cognitive or motor performance over time. The pathogenesis of fatigue remains poorly understood but disease characteristics, including structural and physiologic cerebral alterations as well as immune, endocrine, and psychological factors, may all contribute to its expression. Fatigue therapy has included pharmacologic approaches which have had either methodological limitations (e.g., small sample sizes) or inconclusive results and non-pharmacologic interventions, some of which have been effective in reducing fatigue. Conclusions: Fatigue remains a challenging symptom in MS. The most effective measurement approaches will likely be multidimensional and include both subjective and objective indicators, whereas therapy will likely require more than one type of intervention