In order to investigate the associations between fatigue and depression, disability, and disease subtype, 207 individuals with clinically definite Multiple Sclerosis (MS) were administered the Fatigue Severity Scale and the Zung Self-rating Depression Scale during a regular clinic appointment. Their current level of disability was established using the Expanded Disability Status Scale. Fatigue and depression were highly correlated (r=0.58), even when the depression measure was corrected for items overlapping with fatigue and other symptoms or consequences of MS (r=0.44). Fatigue and disability were also correlated (r=0.33). Multiple regression revealed that both depressed mood and disability were significant predictors of fatigue, together accounting for approximately 23% of the variance in patients' self-reported fatigue. The combined groups of primary progressive (n=45) and secondary progressive patients (n=25) appeared to have higher fatigue scores than relapsing-remitting patients (n=137). However, an analysis of covariance revealed that this apparent difference was in fact attributable almost exclusively to differences in disability among the three subtypes of MS. Other reports of differences in fatigue between subtypes of MS should be re-examined in light of this finding.

Patients with relapsing, primary progressive, and secondary progressive MS were administered the Tower of London and the Stroop Color-Word Interference Test, yielding several measures of executive function and speeded information processing. MS patients' performance was compared with healthy controls and with a clinical control group consisting of patients with rheumatoid arthritis. The MS patients performed the tests more slowly, but did not differ from either group of controls on measures of executive function. Slowing in the speed of information processing was characteristic of MS patients across two basic tasks differing in terms of controlled versus automatic processing and in terms of whether or not rapid responding was an explicit feature of successful performance. Although evident in all subtypes, this slowing was more pronounced in secondary progressive patients and somewhat less pronounced in primary progressive patients. Furthermore, the slowing was unrelated to patients' disability status or level of depression.

The relationship between perceived cognitive functioning and objective cognitive functioning was studied in 221 patients with multiple sclerosis. Perceptions of global cognitive functioning as well as perceptions of performance on specific cognitive tests were assessed. Patients' perceptions of global cognitive functioning in their daily lives were unrelated to their objective performance on the full cognitive test battery. However, patients' perceptions of their performance on specific tasks correlated with their objective performance on those tasks, even though they underestimated their performance on these tasks. The present study also evaluated predictors of patients' perceived cognitive functioning. Depression, anxiety, fatigue, and level of disability predicted perceptions of global cognitive functioning, whereas objective cognitive performance did not. These results add to our understanding of patients' expressed concerns regarding their cognitive functioning in the wake of multiple sclerosis, suggesting that such concerns should be interpreted with caution by clinicians.

Based on the assumption that cognitive impairment in MS is consistent with subcortical dementia, a battery of neuropsychological tests was assembled that included measures of executive function (Tower of London and Wisconsin Card Sorting Test), verbal learning and memory (a paired associates learning test), and speeded information processing (Stroop Color Word Interference Test). The battery was administered to patients with relapsing and primary progressive MS and to healthy controls. Differences between patients and controls occurred on several of the measures. However, when differences with respect to fatigue and depression were statistically controlled, the only differences that remained significant involved measures relating to the speed of information processing. Patients performed more slowly than controls, with the disparity being greater for relapsing patients than for those with primary progressive disease. The slowing was evident on measures of automatic as well as controlled processing and regardless of whether speed was an explicit feature of successful performance or recorded unobstrusively while the patient concentrated on planning a correct solution to a problem. Parallels were noted between cognitive slowing associated with MS and that of normal aging. (JINS, 2004, 10, 948–956.)

The relationship between disability and depression was studied in 188 patients with clinically definite multiple sclerosis (MS). Patients were administered the Zung Self-Rating Depression Scale, Ways of Coping, Uncertainty of Illness Scale, and Hope Scale during their regular clinic appointments. Their current level of disability was rated by the attending physician using the Expanded Disability Status Scale. Even when the depression measure was corrected for items overlapping with other symptoms or consequences of MS, depression was correlated with disability. Depression was also correlated with an array of psychological variables, including uncertainty concerning ones illness, hope, and the use of various emotion-centered, though not problem-centered coping strategies. Multiple regression analyses revealed that none of these psychological correlates mediated or moderated the relationship between disability and depression. Instead, disability, uncertainty, hope, and emotion-centered coping were significant independent predictors of depression, together accounting for approximately 40% of the variance in patients' self-reported depression. The relationship between disability and depression in MS is usually interpreted as evidence that depression is psychogenic and reactive to the demands and limitations of this disease. The demonstration that this relationship is not diminished when an array of potentially intervening psychological variables are included in the analysis raises questions concerning the validity of this interpretation.

Cognitive impairment is more closely associated with physical disability than most previous studies indicate. This relationship appears to be stable throughout the duration of MS, although this conclusion is qualified by the cross-sectional design of the study. Further attention should be paid to cognitive impairment as a possible predictor of the rate of patients' physical decline.

Background Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T2 lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. Objective To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. Methods Seventeen patients with SPMS (Expanded Disability Status Scale = 4.0–7.0; length of MS diagnosis = 19.4±7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. Results The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region (p=0.001). Conclusion The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS.

Deficits in multiple sclerosis (MS) patients' performance on the Stroop Test have been attributed to problems with processing speed and selective attention. Data for 248 MS patients and 178 controls on all three trials of the Stroop were combined using various scoring formulas proposed for assessing processing speed, color difficulty, and interference. The greatest differences between patients and controls involved processing speed. Formulas purporting to measure interference yielded highly inconsistent results: Significant differences between groups were found on two of the most common measures but were in opposite directions. This contradiction stems from the failure of both measures to effectively control for processing speed when assessing interference. Three alternative measures, using relative, ratio, and residualized scores, offer much better indices of interference. When assessed with these alternative measures, interference increased with age, but no differences between patients and controls were found. Difficulties that MS patients have with the Stroop Test are confined to processing speed.