Fatigue symptoms are reported by a majority of patients with multiple sclerosis (MS). Reliable assessment, however, is a demanding issue as the symptoms are experienced subjectively and as objective assessment strategies are missing. The objective of this study was to develop and validate a new tool, the Fatigue Scale for Motor and Cognitive Functions (FSMC), for the assessment of MS-related cognitive and motor fatigue. A total of 309 MS patients and 147 healthy controls were included into the validation study. The FSMC was tested against several external criteria (e.g. cognition, motivation, personality and other fatigue scales). The item-analysis and validation procedure showed that the FSMC is highly sensitive and specific in detecting fatigued MS patients, that both subscales significantly differentiated between patients and controls (p < 0.01), and that internal consistency (Cronbach's alpha alpha > 0.91) as well as test-retest reliability (r > 0.80) were high. Cut-off values were determined to classify patients as mildly, moderately or severely fatigued. In conclusion, the FSMC is a new scale that has undergone validation based on a large sample of patients and that provides differential quantification and graduation of cognitive and motor fatigue.

Although fatigue is one of the most common symptoms of multiple sclerosis, it is yet poorly understood and therefore difficult to manage. To clarify the nature of fatigue we investigated its relationship to depression, physical impairment, personality and action control and compared these variables between a sample of 41 MS patients and 41 healthy controls. Physical impairment was assessed by the EDSS and all other dimensions, using questionnaires. Stepwise linear regression analyses revealed that physical impairment was related to physical fatigue in MS patients. Depression was the main factor influencing fatigue among both, MS patients and controls. What clearly differentiated the two groups was the correlation between fatigue and action control. Decreased levels of action control imply attentional and motivational deficits and were only found in fatigued MS patients. Our study indicates that motivational disturbances might be specific for MS related fatigue.

As attention, processing speed, and working memory seem to be fundamental for a broad range of cognitive performance, the present study on patients with mild forms of relapsing-remitting multiple sclerosis (RR-MS) focused on these domains. To explore subtle neuropsychological changes in either the clinical or fMRI domain, we applied a multistep experimental design with increasing task complexity to investigate global brain activity, functional adaptation, and behavioral responses to typical cognitive processes related to attention and working memory. Fifteen patients with RR-MS (mean age 38 years, 22-49 years, 9 females, mean disease duration 5.9 years (SD = 3.6 years), mean Expanded Disability Status Scale score, 2.3 (SD = 1.3) but without reported cognitive impairment), and 15 age-matched healthy controls (HC; mean age, 34 years, 23-50 years, 6 women) participated. After a comprehensive neuropsychological assessment, participants performed different fMRI experiments testing attention and working memory. In the neuropsychological assessment, patients showed only subtle reduction in learning and memory abilities. In the fMRI experiments, both groups activated the brain areas typically involved in attention and working memory. HC showed a linear in- or decrease in activation paralleling the changing task complexity. Patients showed stronger activation change at the level of the simple tasks and a subsequent saturation effect of (de-)activation at the highest task load. These group/task interaction differences were found in the right parahippocampal cortex and in the middle and medial frontal regions. Our results indicate that, in MS, functional adaptation patterns can be found which precede clinical evidence of apparent cognitive decline.

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To test markers from conventional and diffusion Magnetic Resonance Imaging (MRI) as possible predictors of cognitive outcome following rehabilitation therapy in children with acquired brain injury (ABI). Methods: Twenty-one children (10 boys, mean age 11.6 years, range 7.1-19.4) with stroke or traumatic brain injury underwent MRI including Diffusion Tensor Imaging (DTI) before admission to the rehabilitation centre. The conventional images were scored according to a standardised injury scoring system, and mean Fractional Anisotropy (FA) was determined within the Corpus Callosum (CC), as this structure is hypothesised to play an important role in cognition. Both conventional MRI injury scores and mean FA of the CC and its sub-regions were compared with standard functional cognitive outcome scores. Relationships between MRI indices and cognitive outcome scores were assessed using multiple regression and receiver operating characteristic (ROC) analyses. Results: A backwards regression analysis revealed that the mean FA of the CC body and genu and the supratentorial injury score appear to represent the best predictors of outcome, together with the age at rehabilitation and time in rehabilitation. In the ROC analysis, the mean FA values of the CC body and genu and the infratentorial injury score provided the highest sensitivity, while the mean FA of the CC splenium showed the highest specificity for outcome. Conclusions: The conventional MRI injury scores and DTI metrics from the CC reflect cognitive outcomes following rehabilitation. Neuroimaging methods such as MRI with DTI may therefore provide important markers for cognitive recovery after brain injury.