Reliability of a cognitive endpoint for use in a multiple sclerosis pharmaceutical trial.

OBJECTIVE: Determine reliability and basic psychometric properties of a composite cognitive endpoint, MS-COG, for monitoring change in cognitive function in MS drug trials. BACKGROUND: 50% of MS patients have cognitive impairment that impacts ability to work and quality of life. We selected neuropsychological tests based on sensitivity to MS cognitive impairment, availability of alternate forms, cross-cultural utility, and feasibility for multicenter trials, and assessed the reliability and validity of a composite endpoint, MS-COG. DESIGN/METHODS: Administered SRT, BVMT-R, PASAT, and SDMT to 60 MS patients at 4 US centers twice over 45days, along with symptom inventories by patients and informants. RESULTS: The MS-COG had test-retest reliability of 0.91. Processing Speed and Memory indices had reliabilities of 0.89 and 0.86, with modest practice effects. Reliability was high for the RR MS and SP MS subgroups as well, with correlations of .90 and .93, respectively for MS-COG. Overall, 42% of subjects obtained MS-COG scores in the impaired range, with SP MS subjects performing 0.8 SD below RR MS subjects. Impairment correlated well (r=0.37 to 0.40) with informant reports but was inconsistent with patient report, with the least reliable assessments by those with greater symptom severity. CONCLUSIONS: The MS-COG is a reliable, repeatable measure of MS cognitive functioning that is sensitive to cognitive impairment in SP MS and RR MS patients and feasible for multicenter clinical trials. Further development is warranted.

Rehabilitation of intimacy and sexual dysfunction in couples with multiple sclerosis.

Sexual dysfunction is a highly prevalent symptom of multiple sclerosis (MS), with little published research on effective treatments. This pilot study tested the efficacy of a counseling intervention in nine couples utilizing a quasi-experimental research design. The intervention consisted of 12 counseling sessions, communication with the MS medical treatment team, education, and tailoring symptomatic treatments so they interfere less with sexual function. Repeated measures analysis of variance indicated significant improvements in affective and problem-solving communication, marital satisfaction, and sexual satisfaction during the treatment vs. the waiting list phase of the study (F=1.7, P<.001). MS patients and their spouses reported similar levels of improvement.

Stress and course of disease in multiple sclerosis.

In this prospective study, 96 healthy controls and 101 multiple sclerosis patients were followed up for as many as 6 years, and self-reported stressful events and health status were assessed. The authors evaluated (a) whether patients reported more stressful life events than healthy controls and (b) the bidirectional relationship between stress and functional deterioration among patients. Healthy controls reported more life events than patients, Odds ratio (OR) = 1.13, p < .0001; and this relationship was attributable to healthy controls' reporting more neutral/positive events than patients. A bidirectional relationship was confirmed between stress and illness: there was an increased risk of disease progression when rate of reported stressful events was higher, OR = 1.13, p < .0003, and an increased risk of reported stressful events when rate of disease progression was higher, OR = 2.13, p < .0001. There were no differences in reported stress by level of baseline disability. The authors concluded that multiple sclerosis patients demonstrate a vicious cycle between stress and disease progression.

Helplessness, self-efficacy, cognitive distortions, and depression in multiple sclerosis and spinal cord injury.

The aim of this study was to determine if learned helplessness, self-efficacy, and cognitive distortions would predict depression in a sample of 80 individuals with multiple sclerosis (MS) and 80 individuals with a spinal cord injury (SCI). As MS and SCI usually present with disparate disease courses and etiologies, a secondary objective was to determine if individuals with MS would exhibit greater levels of helplessness, cognitive distortions, and depression and lower levels of self-efficacy than those with SCI. Results indicated that helplessness and self-efficacy significantly predicted depression for both the MS and SCI groups after controlling for confounding variables. Cognitive distortions had no independent effect, indicating that cognitive distortions may have caused feelings of helplessness and low self-efficacy and, in this way, had indirect effects on depression. The MS group exhibited significantly greater levels of depression and helplessness and significantly lower levels of self-efficacy than the SCI group. It was hypothesized that it may have been the combination of an unpredictable course of disease activity and the possibility of being affected by MS in many different ways that produced greater feelings of depression, helplessness, and low self-efficacy in the MS group.

Psychosocial, Affective, and Behavioral Consequences of Multiple SclerosisTreatment of the "Whole" Patient.

Multiple sclerosis (MS) challenges the individual, the family, and society because (1) it can produce wide-ranging functional losses; (2) it is generally progressive with functional losses increasing over time; and (3) its course is unpredictable. Persons affected by MS respond by (1) experiencing changes in their perception of themselves and their world; (2) altering their social roles; and (3) undergoing a variety of emotional responses, especially depression and grief over the losses caused by the illness. Psychosocial interventions that address MS challenges include (1) educational interventions such as lectures, workshops, and books; (2) supportive interventions such as counseling and support groups; (3) psychoeducational interventions such as communication skills training; and (4) somatic therapies such as antidepressants. The unpredictable and progressive course of MS means that affected individuals face a lifetime of periodic challenge. Comprehensive care in MS must address the psychosocial challenges of the illness on a long-term basis. In this way MS care can address the whole patient.

Stress, Multiple Sclerosis, and Everyday FunctioningA Review of the Literature with Implications for Intervention.

Numerous studies have described an association between stress and the onset or exacerbation of multiple sclerosis (MS). Most of the studies that have been conducted to date, however, have had methodological flaws including: (1) retrospective designs, (2) inadequate or absent control groups, (3) small sample sizes, (4) clinical measures that are insensitive to underlying disease activity, and (5) wide variation in the measurement of stress. Animal models of MS have enabled researchers to examine the effects of stress directly in the central nervous system. Stress affects three biological systems that may be dysregulated in MS: the neuroendocrine system, the sympathetic nervous system, and the serotonergic neurotransmitter system. Future stress-MS research should evaluate the relationship between stress and these systems.

A prospective study of depression and immune dysregulation in multiple sclerosis.

This study examined psychologic distress and immune function in patients with chronic-progressive multiple sclerosis participating in a placebo-control trial of cyclosporine. Immune measures included percentages and absolute numbers of CD2+, CD4+, CD8+, Leu-11-b+, HLA-DR (IA+), and transferrin-receptor-positive cells, which were evaluated by immunofluorescence using monoclonal antibodies. Distress was measured with self-report scales. The Expanded Disability Status Scale assessed neurologic disability. Subjects were followed up for 2 years, and their high-depressed and low-depressed times were compared. Times of greater depression were associated with lower CD8+ cell numbers and CD8+%, and a higher CD4/CD8 ratio. CD4+ cell numbers and percent were also higher when subjects were depressed, but only in the placebo group. There were no differences in Expanded Disability Status Scale when subjects were more depressed. Evaluation of a single subject revealed that Ia+ and transferrin-receptor-positive lymphocytes increased 3 months before distress increased. It was concluded that distress is associated with immune dysregulation in multiple sclerosis, although the mechanisms of this association have yet to be delineated.