The psychosocial consequences of pediatric multiple sclerosis.

Although psychological distress and cognitive dysfunction are well documented in adults with multiple sclerosis (MS), they are poorly understood in children with the disease. Psychosocial difficulty experienced by children and adolescents with MS involves factors common to all chronic illnesses in children, as well as MS-specific factors. The psychosocial manifestations of the disease may affect the patient's self-image, role functioning, mood, and cognition to adversely affect schooling, interpersonal relationships, and treatment compliance. Furthermore, the impact of having a family member with MS may affect overall family functioning. Assessment and interventions for psychosocial and cognitive problems in pediatric MS should be multidisciplinary in nature and address the child's functioning at home, school, and among peers, as well as the effect on the family.

Cognitive functioning in children and adolescents with multiple sclerosis.

OBJECTIVE: To examine cognitive functioning in children with multiple sclerosis (MS). METHODS: The authors examined the neuropsychological profile of 37 children with a diagnosis of clinically definite MS and assessed the associations between cognitive function and clinical features. RESULTS: Of 37 children and adolescents evaluated, 35% demonstrated significant cognitive impairment. Cognitive functioning was strongly related to several clinical variables, including current Expanded Disability Status Scale, total number of relapses, and total disease length. The consequences of MS adversely affected academic functioning in over a third of the children. CONCLUSIONS: Cognitive deficits occur in children with multiple sclerosis. Comprehensive treatment planning should involve recognition that they may require academic accommodations for their education.

Donepezil improved memory in multiple sclerosis in a randomized clinical trial.

OBJECTIVE: To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS). METHODS: This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change. RESULTS: Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010). CONCLUSIONS: Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.

Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients.

OBJECTIVE: To relate neuropsychological performance to measures of cerebral injury in persons with MS selected for cognitive impairment. METHODS: Participants were 37 individuals with relapsing-remitting (59.5%) and secondary progressive (40.5%) MS. They were tested at baseline as part of a clinical trial to enhance cognition with an acetylcholinesterase inhibitor. Eligibility criteria included at least mild cognitive impairment on a verbal learning and memory task. A modified Brief Repeatable Battery of Neuropsychological Tests formed the core of the behavioral protocol. Neuroimaging measures were central (ventricular) cerebral atrophy, lesion volume, and ratios of N-acetyl aspartate (NAA) to both creatine and choline. RESULTS: A clear, consistent relation was found between cognitive and MR measures. Among neuroimaging measures, central atrophy displayed the highest correlations with cognition, accounting for approximately half the variance in overall cognitive performance. NAA ratios in right hemisphere sites displayed larger correlations than those on the left. Multiple regression models combining the MR measures accounted for well over half the variance in overall cognitive performance. The Symbol Digit Modalities Test was the neuropsychological task most strongly associated with the neuroimaging variables. CONCLUSIONS: If a strong and stable association can be firmly established between cognitive and MR variables in appropriate subsets of MS patients, it might aid in the investigation of interventions to enhance cognition and modify the course of the disease.