Iris-Katharina Penner

Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)

Background: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. Objective: To recommend a brief cognitive assessment for multiple sclerosis (MS) that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use. Methods: An expert committee of twelve members representing the main cultural groups that have so far contributed considerable data about MS cognitive dysfunction was convened. Following exhaustive literature review, peer-reviewed articles were selected to cover a broad spectrum of cultures and scales that targeted cognitive domains vulnerable to MS. Each was rated by two committee members and candidates scales were rated on psychometric qualities (reliability, validity, and sensitivity), international application, ease of administration, feasibility in the specified context, and acceptability to patients. Results: The committee recommended the Symbol Digit Modalities Test, if only 5 minutes was available, with the addition of the California Verbal Learning Test – Second Edition and the Brief Visuospatial Memory Test – Revised learning trials if a further 10 minutes could be allocated for testing. Conclusions: A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.

MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial.

Objective: Health-related quality of life (HRQOL) is often much reduced among individuals with multiple sclerosis (MS), and incidences of depression, fatigue, and anxiety are high. We examined effects of a mindfulness-based intervention (MBI) compared to usual care (UC) upon HRQOL, depression, and fatigue among adults with relapsing-remitting or secondary progressive MS. Methods: A total of 150 patients were randomly assigned to the intervention (n = 76) or to UC (n = 74). MBI consisted of a structured 8-week program of mindfulness training. Assessments were made at baseline, postintervention, and 6 months follow-up. Primary outcomes included disease-specific and disease-aspecific HRQOL, depression, and fatigue. Anxiety, personal goal attainment, and adherence to homework were secondary outcomes. Results: Attrition was low in the intervention group (5%) and attendance rate high (92%). Employing intention-to-treat analysis, MBI, compared with UC, improved nonphysical dimensions of primary outcomes at postintervention and follow-up (p < 0.002); effect sizes, 0.4–0.9 posttreatment and 0.3–0.5 at follow-up. When analyses were repeated among subgroups with clinically relevant levels of preintervention depression, fatigue, or anxiety, postintervention and follow-up effects remained significant and effect sizes were larger than for the total sample. Conclusions: In addition to evidence of improved HRQOL and well-being, these findings demonstrate broad feasibility and acceptance of, as well as satisfaction and adherence with, a program of mindfulness training for patients with MS. The results may also have treatment implications for other chronic disorders that diminish HRQOL. Classification of evidence: This trial provides Class III evidence that MBI compared with UC improved HRQOL, fatigue, and depression up to 6 months postintervention.

The fatigue scale for motor and cognitive functions (FSMC) : validation of a new instrument to assess multiple sclerosis-related fatigue

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 α > 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.

Analysis of Impairment Related Functional Architecture in MS Patients during Performance of Different Attention Tasks

Abstract. More than 50 % of patients with multiple sclerosis (MS) suffer from cognitive deficits. Attention is one of the most frequently affected cognitive functions. It has been shown that MS patients suffer from a specific but not necessarily from a generalized decrease in performance and that different severity grades of impaired attentional processing can be distinguished. Little is known about patterns of brain activation in MS patients with different grades of attentional deficits. The objective was to examine if different severity grades in attentional impairment are reflected by altered patterns of brain activation in specific attention tasks. In the present study cerebral activation induced by three attention tasks of different complexity was assessed in 14 MS patients and seven healthy controls by functional MRI (fMRI). Based on their performance on the tests recorded off-line with a computerized test battery and during the fMRI investigation, patients were classified as mildly and severely impaired. MS patients with mild impairment showed increased and additional activation of brain areas which were in part not activated in normal subjects. Those were located mainly in the frontal cortex and posterior parietal cortex. This effect decreased with increasing task complexity and was strongest for the alertness task. In MS patients with severe impairment no additional activation was found in prefrontal structures and activation in the premotor cortex was not significantly different from controls. These findings suggest that compensation in MS patients is in part achieved by functional integration of frontal and parietal association areas. The extent of compensation seems to depend on the brains capacity to access additional brain structures. Exhaustion of this capacity may finally lead to severe cognitive impairment.

Working memory training in patients with multiple sclerosis – comparison of two different training schedules

PURPOSE Evaluation of two different training schedules of a computer based working memory training (BrainStim) in patients with multiple sclerosis (MS). METHOD Forty-five MS outpatients were allocated to two different training groups and a control group without training. Patients with treatment received 16 training sessions scheduled either as a high intensity training (4 times per week for 4 weeks) or as a distributed training (2 times per week for 8 weeks). A neuropsychological test battery including self-report measures was applied at baseline and at retest. The baseline assessment was performed twice at an interval of two weeks to control for possible learning effects. RESULTS In the outcome measures training for both intervention groups led to significantly improved fatigue symptoms as well as working memory -, and mental speed performances. Log files recorded during training showed a similar increase in levels of difficulty for both intervention groups as training progressed. No effects were found on short term memory, quality of life or depression. CONCLUSIONS Since comparable improvements were observed in both training groups, BrainStim can be applied as a therapeutic intervention adjusted to the personal agenda of MS patients.

Structural and functional imaging approaches in attention deficit/hyperactivity disorder: Does the temporal lobe play a key role?

Attention deficit/hyperactivity disorder (ADHD) is characterized by widespread structural and functional abnormalities in the brain. We applied different structural imaging techniques such as voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and magnetization transfer imaging (MTI) to study anatomical differences between boys with ADHD and healthy controls, as well as functional magnetic resonance imaging (fMRI) together with independent component analysis (ICA) to detect functional alterations. 14 boys with ADHD and 12 controls were included in our study. Results of DTI showed the expected differences in frontal and cerebellar white matter. VBM and MTI indicated group differences in the temporal lobe. Applying ICA to fMRI data, we extracted four components; two positively correlated to our working memory paradigm and two negatively correlated. Positive components included activation in frontal and parietal regions. Negative components showed activation in anterior and posterior cingulate cortex/precuneus and temporal regions, and were interpreted as forming part of the default mode network. Group differences in the inferior temporal lobe were detected. Applying different techniques, we found differences between boys with ADHD and controls mainly located in the temporal lobe. Therefore, we postulate that research on ADHD should broaden its scope by including the temporal lobe as a potentially important locus of abnormalities in ADHD.

Effects of methylphenidate on working memory functioning in children with attention deficit/hyperactivity disorder

BACKGROUND AND AIMS Children with attention deficit/hyperactivity disorder (ADHD) often show deficits in working memory performance. Methylphenidate (MPH) is an effective medication to improve these cognitive difficulties. This study aimed to clarify which effect MPH induces on the underlying functional networks of working memory. METHODS Fourteen boys diagnosed with ADHD and 12 healthy controls were investigated using functional magnetic resonance imaging (fMRI). Each patient was tested twice, once with medication and once without. The fMRI experiments consisted of three verbal N-back tasks with increasing difficulty. Functional images were acquired on a 3 Tesla head scanner. RESULTS On the behavioral level, medicated patients performed similar to healthy controls and significantly better than without medication. On the functional level, patients showed the expected frontal and parietal activations, which were more pronounced in the 2- and 3-back tasks. Healthy controls showed significantly more activation in these regions and additional activation in the cerebellum. Interestingly, patients showed an additional effect of laterality. Left-sided frontal and parietal activation in patients was significantly less pronounced than in controls. CONCLUSION Functional data indicate different activation patterns in verbal working memory tasks between healthy controls and patients with ADHD irrespective of medication condition. Intake of MPH led to a clear improvement on a behavioral level. However, this effect was not reflected by changes in functional brain organization. MPH-induced changes leading to better performance in verbal working memory tasks might be very subtle and therefore not detectable by fMRI.

Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis

Background: Cortical lesions (CLs) have been reported to be a better predictor for cognitive impairment than white matter (WM) lesions in relapsing–remitting multiple sclerosis (RRMS). Objectives: The objectives of this article are to investigate the contribution of CLs and WM lesions to cognitive impairment in 91 patients with MS and clinically isolated syndrome, and to test potential associations of CLs and WM lesions with fatigue and depression. Methods: Lesions were scored and segmented on 3D double inversion recovery sequences, according to their location (cortical, WM). Normalised grey matter volume was also determined. Cognitive performance was assessed with the SDMT and PASAT-3, fatigue with the FSMC and depression with the German version of the CES-D. Results: CL volume did not correlate with fatigue or depression, but correlated significantly with both neuropsychological outcome measures: PASAT-3 (r = −0.275, p = 0.009) and SDMT (r = −0.377, p < 0.001). Multiple regression analyses with age, WM lesions, CLs and GM volume as independent variables, however, did not reveal CL volume as a significant predictor of neuropsychological outcomes, whereas WM lesion volume significantly predicted SDMT and by trend PASAT performance. Conclusions: These findings suggest a role of WM lesions in the development of cognitive deficits, especially information-processing speed, which may be higher than previously assumed. Abbreviations: CES-D: Center for Epidemiologic Studies Depression scale (ADS-L: Allgemeine Depressions Skala-L, German version of CES-D), CIS: clinically isolated syndrome, CL: cortical lesion, DIR: double inversion recovery, EDSS: Expanded Disability Status Scale, FSMC: fatigue scale for motor and cognitive functions, GM: grey matter, MRI: magnetic resonance imaging, MS: multiple sclerosis, PASAT-3: paced auditory serial addition test 3s, PPMS: primary progressive multiple sclerosis, RRMS: relapsing–remitting multiple sclerosis, SDMT: symbol digit modalities test, SPM: statistical parametric mapping, SPMS: secondary progressive multiple sclerosis, WM: white matter

Fatigue in multiple sclerosis : relation to depression, physical impairment, personality and action control

Athough 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. Multiple Sclerosis 2007; 13: 1161—1167. http://msj.sagepub.com

Cognitive impairment and cortical reorganization in children with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is associated with mild cognitive deficits, especially language impairment. This study aimed to clarify whether children with BECTS with left‐ or right‐hemispheric, or bilateral focus have specific neuropsychological language deficits when compared to healthy controls, whether these deficits correlate functionally with language network organization (typical vs. atypical), and whether cofactors such as duration, handedness, and medication have a relevant impact on language reorganization processes.