The extent and pattern of demyelination in the cerebral cortex was determined in 78 tissue blocks from the brains of 20 multiple sclerosis (MS) patients and 28 tissue blocks from 7 patients without neurological disease. Tissue blocks from 4 predetermined areas (cingulate gyrus, frontal, parietal, and temporal lobe) were studied, irrespective of macroscopically evident MS plaques. All tissue blocks contained cerebral cortex and periventricular and/or subcortical white matter. One hundred and nine demyelinating lesions were detected in the cerebral cortex, of which 92 (84.4%) were purely intracortical and 17 (15.6%) were lesions extending through both white and gray matter areas. In 5 of the 20 MS brains, subpial demyelination was extensive in the 4 widely spaced cortical areas studied, thus considered to represent a general cortical subpial demyelination. The percentage of demyelinated area was significantly higher in the cerebral cortex (mean 26.5%, median 14.1%) than in white matter (mean 6.5%, median 0%) (p = 0.001). Both gray and white matter demyelination was more prominent in the cingulate gyrus than in the other areas examined (p < 0.05). These results indicate that the cerebral cortex is likely to be a predilection site for MS lesions and identify general cortical subpial demyelination as a distinct pattern occurring in a significant subpopulation of MS patients.

The SF-36 captures the broad effects of MS, and the results showed that patients also are bothered frequently with health problems such as bodily pain and low vitality. These problems, which are not reflected in the Expanded Disability Status Scale, should be given more attention in the treatment of MS and when evaluating interventions.

Most multiple sclerosis (MS) patients experience some sexual, bladder and/or bowel dysfunction during the course of the disease--one of MS most disabling features. This study estimated the frequency of these problems among patients, two to five years after diagnosis, and investigated how these problems are associated with health-related quality of life (using the Multiple Sclerosis Quality of Life-54 questionnaire). The study population comprised a cohort of patients (n = 56), diagnosed in a three-year period, in Hordaland County, Norway. The patients were examined clinically, including scoring of the Expanded Disability Status Scale (EDSS), and completed questionnaires related to bowel and bladder dysfunction, sexual problems and health-related quality of life. More than half the patients had bladder and sexual problems. The frequency of self-reported bladder problems corresponded to the relatively high levels of residual urine found. The presence of these problems was associated with lower scores on the quality of life scales. Further, the bowel problems reported were markedly associated with the quality of life scores. Since treatments and preventive strategies can manage many of these problems, we suggest increasing the focus on these aspects of the disease when consulting patients, including at early stages.

The present study examined the extent and distribution of lymphocyte infiltration in demyelinated lesions in the cerebral cortex of multiple sclerosis (MS) patients. Tissue sections from the brain of 10 MS patients and five patients without neurological disease were double labeled for myelin basic protein and the lymphocyte markers CD3, CD4, CD8, CD45RO, and CD20. The highest density of CD3-positive T cells was found in MS white matter lesions (40.4/10 high power fields (hpf)). Fewer T cells were detected in cortical lesions that extended through both white and gray matter (12.1/10 hpf; P < 0.001). The lowest number of T cells was detected in intracortical demyelinated lesions (1.1/10 hpf). This was equal to the lymphocyte density in nondemyelinated cerebral cortex within the same tissue block (1.1/10 hpf) or cerebral cortex in control brains (1.8/10 hpf). A similar distribution was found using the CD4, CD8, and CD45RO markers. CD20-positive B cells were scarce in all specimens examined. These data indicate that areas of intracortical demyelination in chronic MS are not associated with an increased number of lymphocytes, or an altered distribution of lymphocyte subsets, when compared with control areas in MS and control patients. This finding indicates that the extent of lymphocyte infiltration in MS lesions is dependent on lesion location.

BackgroundChronic fatigue syndrome (CFS) is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.Methods and FindingsIn this double-blind, placebo-controlled phase II study (NCT00848692), 30 CFS patients were randomised to either Rituximab 500 mg/m2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV) was not detected in any of the patients.The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003). Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8–44). Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed), with differences between the Rituximab and Placebo groups between 6–10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.ConclusionThe delayed responses starting from 2–7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact future research efforts in CFS.Trial registrationClinicalTrials.gov NCT00848692

Background: To study the impact of fatigue in young ischaemic stroke patients. Methods: The Fatigue Severity Scale score was obtained in 192 patients (mean time 6.0 years after the stroke) and 212 controls. Results: Fatigue was associated with cerebral infarction in a multivariate analysis of patients and controls (p = 0.002). Fatigue was independently associated with unfavourable functional outcome (p = 0.001), depression (p < 0.001), and basilar artery infarction through interaction with the modified Rankin Scale score (p = 0.047) in patients. Conclusion: Fatigue is frequent in young adults with cerebral infarction. Stroke-related factors independently associated with fatigue include functional outcome. Stroke location may influence fatigue.

Objectives To identify MRI biomarkers associated with long-term disability progression in patients with multiple sclerosis (MS), and to define the rate of evolution of global, tissue-specific and regional atrophy in patients with MS over long-term. Methods MRI of the brain and clinical neurological assessment was performed in 81 patients at time of first visit and after 5 and 10 years of follow-up. MRI was acquired on 1.5 T scanners. T1-lesion and T2-lesion volumes (LVs) were calculated. Global and tissue-specific atrophy changes were longitudinally assessed, using a direct measurement approach, by calculating percentage volume changes between different time points. Regional tissue volumes for the subcortical deep grey matter (SDGM) structures were also obtained. Disability progression was defined as an increase in Expanded Disability Status Scale of ≥1.0 compared to baseline at 5-year and 10-year follow-up. Results Over 5 years, patients with disability progression showed significantly increased loss of whole brain (−3.8% vs −2.0%, p<0.001), cortical (−3.4% vs −1.8%, p=0.009) and putamen volume changes (−10.6% vs −3.8%, p=0.003) compared to patients with no disability progression. No significant change in white matter (WM) volume was observed when comparing progressing and non-progressing patients. Over 10 years, there was a trend for greater decrease in whole brain volume (−5.5% vs −3.7%, p=0.015) in the progressing patients. No significant changes in LV measures were detected between the patients with and without disability progression. Conclusion This long-term study shows that whole brain, cortical and putamen atrophy occurs throughout the 10-year follow-up of this MS cohort and is more pronounced in the group that showed disability progression at 5, but not at 10 years of follow-up. Overall, GM atrophy showed better association with disease progression than WM atrophy over 5-year and 10-year follow-up.

Background and Purpose— We sought to compare health-related quality of life (HRQoL) in young adults with ischemic stroke on long-term follow-up with controls and to evaluate HRQoL in clinically relevant patient subgroups. Methods— HRQoL was determined with the use of the 8 subscales of the Short-Form General Health Survey (SF-36). Subgroups of patients were defined by sex, age, functional status (modified Rankin Scale), marital status, education, depression (Montgomery-Åsberg Depression Rating Scale), and fatigue (Fatigue Severity Scale). SF-36 scores among patients were compared with SF-36 scores among age- and sex-matched controls and SF-36 scores available from the general Norwegian population. Results— SF-36 scores were obtained after a mean follow-up of 6.0 years among 190 young adults with ischemic stroke during 1988–1997 and among 215 responding controls (55%). The difference in HRQoL between patients, controls, and the general Norwegian population was restricted mainly to the 3 subscales physical functioning, general health, and social functioning ( P <0.001). Subgroup analysis showed significantly reduced scores for all SF-36 items among patients who were depressed, suffered from fatigue, or unemployed. Linear regression analysis showed that fatigue and depression were major independent variables correlated with low HRQoL. Conclusions— Compared with controls and the general Norwegian population, low level of HRQoL among young adults with ischemic stroke was most pronounced in regard to physical functioning. Early identification and treatment of depression, fatigue, and physical disability may potentially improve HRQoL among stroke patients.