Search

The Wellbeing Game uses game design elements to promote wellbeing. Players document their daily activities in the game and categorize them to one or more of five wellbeing-related factors. The users join teams and can create team events to work together and improve their wellbeing status. The present study aims to review the application and the theoretical base of 'TheWellbeing Game', to adapt it to the German context, and to evaluate its health effects in different settings. Additional aims are to analyze the current state of research regarding the links between health, wellbeing, and gamification and to identify crucial game design elements that have to be implemented in the application in order to address the needs of competence, autonomy, and social relatedness according to the self-determination theory. The Wellbeing Game uses game design elements to promote wellbeing. Players document their daily activities in the game and categorize them to one or more of five wellbeing-related factors. The users join teams and can create team events to work together and improve their wellbeing status. The present study aims to review the application and the theoretical base of ‘The Wellbeing Game’, to adapt it to the German context, and to evaluate its health effects in different settings. Additional aims are to analyze the current state of research regarding the links between health, wellbeing, and gamification and to identify crucial game design elements that have to be implemented in the application in order to address the needs of competence, autonomy, and social relatedness according to the self-determination theory.

Work competencies can be defined as learned abilities to adequately perform a task, role or mission (Roe 2002). In the workplace context, work-integrated learning approaches are particularly promising approaches for developing work competencies while ensuring transfer and relevance for practice (Sonntag and Stegmaier 2007). However, apart from developing competencies, it is also important that newly acquired competencies are actually applied in the workplace. Hereby motivation plays an essential role. Work environments, which support feelings of competence, autonomy and relatedness, are the foundation for maintaining motivation (Ryan and Deci 2000).

Gamification, as opposed to serious gaming, focuses on the integration of certain elements and mechanics from the field of gaming and game design into an existing (nongaming) environment. Typical game design models do not meet the requirements of implementing a gamification application in total because they focus on the development of a holistic game. An implementation model for the gamification of business processes should focus on the integration of game elements and mechanics into an existing work context instead. An implementation model was designed to fulfill these demands and will be presented in this paper. The so-called GameLog Model can be divided into three major phases: the analysis and exploration phase, the design and realization phase, and the evaluation and reflection phase. Within the analysis and exploration phase, the context that should be gamified is described on a granular level to find integration points for the game elements that do not change the process. In the design and realization phase, the gamification application is developed and implemented in the nongaming context. During the evaluation and reflection phase, the success of the application, as well as the acceptance of the employees, is measured. Results lead to a possible redesign. The model was evaluated by designing and testing a gamification application for the field of material handling. The gamification prototype was created for the process of manual order picking. Significant results could be achieved in fostering motivation and improving performance among workers in this process. Hence, the introduced model does work to successfully implement a gamification application into a business process. Gamification can also be seen as a useful approach to foster motivation and increase the performance of employees.

Im Rahmen dieses Kapitels werden theoretische Modelle zur Erklarung der Wirkung von Gamification auf Motivation beschrieben. Zunachst werden unterschiedliche motivationstheoretische Ansatze kurz miteinander verglichen (4.1). Im Anschluss erfolgt die Darstellung der Selbstbestimmungstheorie der Motivation, die als Rahmenkonzept in dieser Arbeit verwendet wird (4.2).

Im Rahmen dieses Kapitels wird die Wirkung von Gamification auf Leistung diskutiert. Zunachst wird der Leistungsbegriff naher betrachtet (5.1), im Anschluss erfolgt die Betrachtung von Moglichkeiten zur Leistungsforderung (5.2). Auch im Rahmen dieses Kapitels dient die Selbstbestimmungstheorie der Motivation nach Deci und Ryan (1985) als theoretische Grundlage und wird fur die Betrachtung eines moglichen Zusammenhangs von Leistung und Bedurfnisbefriedigung herangezogen (5.2.1).

Objective: The objective of this study was to assess the effect of treatment with interferon (IFN) β-1a, 44 µg subcutaneously (sc) three times weekly (tiw), on clinical and magnetic resonance imaging (MRI) outcomes in patients with relapsing multiple sclerosis (MS) following mitoxantrone therapy. Methods: This was an open-label, randomized, multicentre, rater-blinded, 96-week observational study conducted in Germany. Clinically stable patients with relapsing forms of MS, who had discontinued mitoxantrone treatment 1–6 months before study entry, were randomized to IFN β-1a sc 44 µg tiw, or no treatment. The primary endpoint was time to first relapse. Secondary endpoints included the number of relapse-free patients, disease activity assessed by MRI and time to 3-month confirmed Expanded Disability Status Scale (EDSS) progression, all at week 96. Results: A total of 30 patients were randomized (intent-to-treat population: 14 IFN β-1a, 15 untreated; one patient from the safety population discontinued the study after 25 days owing to an adverse event and without providing any postbaseline efficacy data, and was thus excluded from the intent-to-treat population). Overall, 71.4% (10/14) of patients in the IFN β-1a group remained relapse free over 96 weeks, versus 46.7% (7/15) in the untreated group ( p = 0.26). IFN β-1a delayed the time to first relapse versus no treatment ( p = 0.14); time to first relapse (25th percentile) was 95.4 (IFN β-1a) versus 46.0 weeks (no treatment). Confirmed EDSS progression was observed in five patients in each treatment group. Mean change in EDSS score was 0.3 in both groups ( p = 0.79). Changes in the number or volume of T1 and T2 lesions at week 96 were not significantly different between treatment groups ( p > 0.05). There were no new or unexpected adverse events related to IFN β-1a treatment. Conclusions: Several endpoints appeared to show a benefit of IFN β-1a treatment, but no significant differences could be detected owing to the small sample. Therefore, these data only permit, at best, tentative conclusions about the disease course in patients with MS after de-escalation from mitoxantrone and continuation with or without IFN β-1a. Larger confirmatory studies are required.

Background: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. Objectives: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. Methods: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20–60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. Results: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently ( p Conclusions: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Multiple sclerosis (MS) is an inflammatory disease the central nervous system. Its first manifestation and clinical course of the disease is highly heterogeneous. The diagnosis is based on the verification of neurological deficits, the development of the clinical course and the magnetic resonance imaging (MRI) of the head and spine. The therapy comprises disease modifying drugs (DMD), therapy for acute relapses and escalation therapy according the German MS-Therapy-Consensus-Group (MSTKG). An early therapy initiation and a systematic therapy of acute relapses and symptoms determine the modern MS-management.

In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS ( n = 34) and SPMS ( n = 197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group ( P = 0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks ( P = 0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group ( P = 0.028). The difference was significant in PPMS ( P = 0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance ( P = 0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS. Multiple Sclerosis 2007; 13: 1107—1117. http://msj.sagepub.com

We studied two adult patients with myalgia and muscular fatigability during prolonged physical exercise. Serum creatine kinase was increased and muscle biopsy revealed a lipid storage myopathy affecting predominantly the type I fibres. Skeletal muscle carnitine content was reduced to 15% and 21% of the normal mean values, while serum carnitine levels were either normal or decreased. Four months of oral therapy with L-carnitine (3 g per day) resolved the clinical symptoms completely in both patients, and a subsequent muscle biopsy confirmed a marked reduction of lipid storage, along with increased muscle carnitine levels. The analysis of renal carnitine excretion and the exclusion of possible secondary carnitine deficiencies in both patients are compatible with mild defects of the carnitine transporter in one patient and of carnitine biosynthesis in the other. Since myalgia and muscular fatigue are frequent but unspecified complaints of otherwise clinically unremarkable adult patients, it is important to identify myopathies associated with primary carnitine deficiency because they may be amenable to treatment.

To assess whether TGF-beta isoforms are significantly increased after intravenous immunoglobulin (i.v.IG) infusion in the plasma of patients with multiple sclerosis (MS), 19 patients with clinically definite MS were enrolled in a double blind placebo controlled i.v.IG study. TGF-beta1, TGF-beta2, TGF-beta3 plasma concentrations were measured prior and directly after i.v.IG infusions by specific ELISA. Compared to the placebo group, we found a significant increase in the plasma levels of all three TGF-beta isoforms in patients treated with i.v.IG. The significantly increased TGF-beta plasma concentrations in treated patients suggest an additional, immediate mechanism of action that may accompany the molecular effects of i.v.IG therapy in MS. The variable amount of the potent anti-inflammatory TGF-beta isoforms within the i.v.IG preparations may exert a differentiated view regarding the manifold indications of i.v.IG therapy.

Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo , the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T2 hyper‐intense and T1 hypo‐intense lesion volumes. High‐resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age‐matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject’s entire brain and computed cross‐subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t ‐tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] brain regions was observed, even early in the course of the disease or in patients with mild disability. Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the motor cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in vivo measurement of cortical thickness is feasible in patients suffering from multiple sclerosis. The data provide new insight into the cortical pathology in multiple sclerosis patients, revealing focal cortical thinning beside an overall reduction of the cortical thickness with disease progression. Received October 24, 2002. Revised February 24, 2003. Second revision March 27, 2003. Accepted March 28, 2003

Facioscapulohumeral muscular dystrophy (FSHD) is associated with the deletion of a variable number of 3.3-kb subunits of a tandemly arranged repeat (D4Z4) on chromosome 4q35. EcoRI/BlnI fragments in the range of 10-35 kb are currently defined as disease-associated. Diagnosis of FSHD is frequently complicated by interchromosomal exchange with a homologous locus on 10q26. We present clinical and laboratory data of six subjects from two unrelated families with a marked FSHD phenotype and EcoRI/BlnI fragments of 39 and 33 kb, respectively. Origin on chromosome 4q35 was confirmed by haplotype analysis in the first family and was supported by pulsed field gel electrophoresis data in the second family. Our data further confirm the existence of a region of overlap of normal and pathological fragments. Fragments from this region can obviously be associated with marked FSHD phenotypes. Furthermore, application of linked markers and resolution of all EcoRI/BlnI fragments by pulsed field gel electrophoresis in addition to routine laboratory tests considerably augments the information obtained from molecular tests, upon which genetic counselling can then be based.

Nuclear power plants are operated in about 30 countries. The implementation of nuclear power plants in the future is being discussed in a similar number of other countries. Some of these plans are at an advanced stage; many others are at the stage of very preliminary considerations.

Logistics is concerned with effectively managing the flow of materials and supplies for production, commerce and other purposes (Christopher, 2003). Transport logistics deals with resource flows on a large scale level, as it involves transport by land, water, and air. A second domain of logistics is intralogistics, which is concerned with the internal handling of materials and supplies within specific production sites or intermediate storage facilities (Arnold, 2006). This paper focuses on intralogistics or, more specifically, on one of its central tasks, order picking.

Neurocognitive involvement in multiple sclerosis (MS) is heterogeneous with some authors suggesting a frontal pattern in patients with predominantly frontal lesions. To assess the relationship between the distribution of lesions and two cognitive components (visual N2, auditory P3a) of the event-related brain potential (ERP) receiving contributions from frontal lobe structures, we performed a combined ERP and magnetic resonance imaging (MRI) study. Thirty-four MS patients were assigned to “low lesion volume, (LLV)”(n = 12), “high lesion volume, (HLV)” (n = 12) and “frontal lesion volume, (FLV)” (n = 10) groups according to lesion volume and distribution on T2-weighted MRI-scans of the brain. ERPs in visual and auditory classification tasks as well as neuropsychological tests were carried out in patients and control subjects (n = 15). The index for automatic feature registration, the N2 component with its mainly frontal contribution in the visual task, was significantly reduced in amplitude in the FLV and HLV groups (both p < 0.01 vs. controls). Moreover its amplitude correlated with lesion volume (r=0.64, p < 0.001). In contrast neither P3a nor P3b subcomponents with a multiple generator nature in the auditory task varied systematically with lesion volume or distribution. Total lesion volume rather than predominant lesion arrangement appears to be the most important factor in neurocognitive changes in MS. This is most consistent with the view that MS lesions lead to partial disconnections within widespread cortical networks which in turn produce a pattern of neuropsychological deficits that reflect total lesion load more than lesion distribution.

Mitochondrial pathology is an early observation in motor neurons and skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). To clarify the relevance of this finding, we determined the effects of a 1-month oral administration of creatine on (1)H NMR-visible metabolites in the motor cortices of 15 controls and 15 patients with sporadic ALS, most of whom had mitochondrial pathology in skeletal muscle. In the motor cortex of the ALS group the N-acetylaspartate (NAA)/creatine (Cr(t)) metabolite ratio was lower than in our control group, indicating NAA loss. Upon creatine supplementation we observed in the controls a decline in the NAA/Cr(t), NAA/choline (Cho), glutamate + glutamine (Glx)/Cr(t), and Glx/Cho metabolite ratios. In contrast, in the ALS patient group the NAA/Cr(t) and the NAA/Cho metabolite ratios remained unchanged, while the Glx/Cr(t) and Glx/Cho metabolite ratios decreased. These data are compatible with the interpretation that creatine supplementation causes an increase in the diminished NAA levels in ALS motor cortex as well as an increase of choline levels in both ALS and control motor cortices. Because NAA is synthesized by mitochondria in an energy-dependent manner and the NAA/Cho metabolite ratios in the ALS motor cortices were found to be correlated to the degree of mitochondrial pathology in ALS skeletal muscle, our results can be explained by a deficiency of enzymes of mitochondrial respiratory chain in the ALS motor cortex which might affect motor neuron survival.

OBJECTIVE—To assess the quality of life (QoL) of patients with multiple sclerosis in France, Germany, and the United Kingdom with a cross sectional study. METHODS—Patients were classified into three severity groups according to the expanded disability severity scale (EDSS); stage I, II, and III, corresponding to mild (EDSS 1.0-3.5), moderate (EDSS 4.0-6.0), or severe (EDSS 6.5-8.0) multiple sclerosis respectively. Ninety patients with multiple sclerosis and 30 control patients without multiple sclerosis were recruited in each country. Control patients were matched to the patients with multiple sclerosis according to age and sex. Quality of life was assessed using the functional status questionnaire (FSQ). RESULTS—The aspects of QoL that were mostly affected in the three countries under study were physical function and general wellbeing. Social role function decreased with increased severity of disease in France and in particular in Germany. Multiple sclerosis did not seem to have an impact on psychological function. The QoL of control patients was systematically higher than that of patients with multiple sclerosis. CONCLUSIONS—Use of such a generic scale showed that progression of multiple sclerosis is accompanied by a decrease in QoL and suggested that this could be a relevant measurement in assessing the effect of treatment and progression of disease. Variation between countries, however, may be important.

We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point: (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.

Neurodegeneration following inflammatory injury is considered to be a pathological correlate of irreversible disability in patients with multiple sclerosis. The availability of neurotrophins could influence the probability or rate of disease progression and the time of onset. The BDNF-Val66Met-polymorphism leads to altered intracellular transport and secretion of BDNF, and is thus a logical candidate for a gene that influences susceptibility and, more specifically, the clinical course of multiple sclerosis. In order to test this hypothesis we genotyped the polymorphism in 951 UK multiple sclerosis trio families, but found no evidence for association before (p=0.63) or after stratification for clinical course (p=0.73).

Background Prevalence rates of cognitive impairment (CI) in multiple sclerosis (MS) vary between 40% and 80%. Differences in classification criteria for CI may explain this variance. Objective This study reviewed and compared classification criteria for CI in patients with early and late MS. Methods The paper consists of two parts: a systematic review of published classification criteria and the presentation of new data. Criteria were reviewed in respect to percentage of abnormal parameters and cut-offs concerning standard deviations. Thereafter, criteria were applied to cognitive data of 25 patients with early MS (duration ≤ 2 y), 52 matched patients with late MS (≥ 12 y), and 75 matched controls. The test battery assessed alertness, divided attention, mental flexibility, verbal and visual learning, memory, and visuospatial abilities. Results Seventy classification criteria were revealed and grouped into 20 distinct approaches that can be subdivided into three basic classification strategies. Most commonly, CI was defined as performing 1.5 SD or 2 SD below the normative mean in 18–30% of test parameters (n = 42). Other criteria utilized cognitive domains (n = 6), composite indices (n = 8), or combinations of cut-offs and strategies. The stringency of the criteria was correlated with the prevalence rate of CI (r = − .43) and disease duration (r = .48). In the new data, a substantial effect of classification criteria was found with a prevalence rate ranging from 0 to 68% in early and 4 to 81% in late MS. Increased rates of CI in patients vs. controls were found following 18 out of 20 criteria in the sample of late MS. In early MS, an increased rate of CI was only found following a liberal 1.5 SD cut-off criterion. Inter-rater reliability between all criteria was moderate. However, between criteria of comparable stringency the inter-rater reliability was found to be strong. Conclusion Classification based on different published criteria is not fully comparable and criteria need to be better homogenized.

Background and purpose The trend towards a shorter stay in rehabilitation clinic has implications for future language therapy. Constraint-induced aphasia therapy (CIAT) is administered 3 h per day for a total of 30 h of treatment. It was evaluated for patients with chronic aphasia. In the present study we investigated the efficacy of a modified CIAT schedule and included patients with sub-acute stroke. We conducted a randomised, single-blind, parallel-group study. The results were compared to those of patients who received identically intensive treatment focusing on conventional aphasia therapy. Methods Fifty patients were treated with our modified version of CIAT and 50 received a standard aphasia therapy at the same intensity and duration. Inclusion criteria were clinical diagnosis of first-ever stroke, aphasia in the sub-acute stage and German speakers. Language function was evaluated using the Aachen Aphasia Test and the Communicative Activity Log directly before therapy onset, after the training period and at 8-week and 1-year follow-ups. Results Patients of both groups improved significantly in all sub-tests of the Aachen Aphasia Test Battery. The improvements remained stable over a 1-year follow-up period. Patients and relatives of both groups rated daily communication as significantly improved after therapy. Conclusions Both CIAT and conventional therapy performed with equal intensity are efficacious methods for patients with sub-acute aphasia. The modified CIAT schedule is practical in an everyday therapeutic setting. Our results indicate that a short-term intensive therapy schedule in the early aphasia stage leads to substantial improvements in language functions. Clinical Trial Registration Information Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01625676

Objective: To report the clinical and immunological response to immunosuppressive treatment with cyclophosphamide in two patients with paraneoplastic cerebellar degeneration. Design: Case reports. Clinical and immunological follow-up data were available for 4½ years in the first patient and for 2 years in the second patient. Setting: A 1500-bed university hospital and a 1200-bed university teaching hospital. Intervention: Cyclophosphamide intermittent treatment. Main Outcome Measure: Clinical disability. Results: One of the patients, who was treated from an early stage, recovered completely. The other patient showed a partial clinical response. While the two patients were receiving a maintenance regimen with cyclophosphamide, the conditions of both patients remained stable for at least 2 years. In both patients, intrathecal antibody synthesis declined considerably. Conclusion: Early induction of immunosuppressive therapy with cyclophosphamide should be tried in treating patients with paraneoplastic cerebellar degeneration.

Background: In multiple sclerosis inflammation is primarily injurious to the central nervous system, but its therapeutic suppression might inhibit repair-promoting factors. Objectives: We aimed at better describing the complexity of biological effects during an acute relapse and analysed the effects of intervention with high-dose i.v. glucocorticoids and immunomodulatory treatment with interferon-beta (IFNβ). Methods: We studied the intracellular expression levels of the pro-inflammatory mediators tumour necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) together with the neurotrophins ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in freshly isolated peripheral blood mononuclear cells of multiple sclerosis patients during an acute relapse, after intervention with i.v. methylprednisolone and at baseline, using a highly quantitative flow-cytometric approach. Results: We demonstrated the expression of CNTF in human leucocytes. We showed that CNTF levels differed in acutely relapsing multiple sclerosis patients compared with controls and increased after corticosteroid treatment. CNTF can counteract the toxicity of TNFα towards oligodendrocytes and we found TNFα increased during acute relapses. Following corticosteroids, neither TNFα nor iNOS expression was reduced. Levels of BDNF were not affected by glucocorticoids, but increased during IFNβ therapy. However, IFNβ also increased the expression of iNOS and major histocompatibility complex class I (MHC-I), underlining its immunomodulatory potential. Conclusions: Multiple sclerosis patients might benefit from reparative, and not solely from anti-inflammatory, effects of glucocorticoids. Interactive effects of glucocorticoid- and IFNβ-treatment need to be considered to improve neuroprotection and remyelination resulting from immunomodulatory treatment.

Multiple sclerosis (MS) is an inflammatory disease the central nervous system. Its first manifestation and clinical course of the disease is highly heterogeneous. The diagnosis is based on the verification of neurological deficits, the development of the clinical course and the magnetic resonance imaging (MRI) of the head and spine. The therapy comprises disease modifying drugs (DMD), therapy for acute relapses and escalation therapy according the German MS-Therapy-Consensus-Group (MSTKG). An early therapy initiation and a systematic therapy of acute relapses and symptoms determine the modern MS-management.

1477-0970 (Electronic) 1352-4585 (Linking) Journal Article; This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing-remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion burden, and the sample sizes needed to demonstrate a treatment effect on MTR metrics in placebo-controlled MS trials were also investigated. Bimonthly brain conventional and MT MRI scans were acquired from 42 patients with RRMS enrolled in the placebo arm of a 14-month, double-blind trial. Longitudinal MRI changes were evaluated using a random effect linear model accounting for repeated measures, and adjusted for centre effects. The Expanded Disability Status Scale (EDSS) score remained stable over the study period. A weak, but not statistically significant, decrease over time was detected for normal-appearing brain tissue (NABT) average MTR (-0.02% per visit; p = 0.14), and MTR peak height (-0.15 per visit; p = 0.17), while average lesion MTR showed a significant decrease over the study period (-0.07% per visit; p = 0.03). At each visit, all MTR variables were significantly correlated with T2 lesion volume (LV) (average coefficients of correlation ranging from -0.54 to -0.28, and p-values from

MOTOR IMPAIRMENTS ARE COMMON AFTER STROKE but efficacious therapies for these dysfunctions are scarce. Extending an earlier study on the effects of music-supported training (MST), behavioral indices of motor function were obtained before and after a series of training sessions to assess whether this new treatment leads to improved motor functions. Furthermore, music-supported training was contrasted to functional motor training according to the principles of constraint-induced therapy (CIT). In addition to conventional physiotherapy, 32 stroke patients with moderately impaired motor function and no previous musical experience received 15 sessions of MST over a period of three weeks, using a manualized, step-bystep approach. A control group consisting of 15 patients received 15 sessions of CIT in addition to conventional physiotherapy. A third group of 30 patients received exclusively conventional physiotherapy and served as a control group for the other three groups. Fine as well as gross motor skills were trained by using either a MIDI-piano or electronic drum pads programmed to emit piano tones. Motor functions were assessed by an extensive test battery. MST yielded significant improvement in fine as well as gross motor skills with respect to speed, precision, and smoothness of movements. These improvements were greater than after CIT or conventional physiotherapy. In conclusion, with equal treatment intensity, MST leads to more pronounced improvements of motor functions after stroke than CIT.

Background Detecting malingering or exaggeration of impairments in brain function after traumatic brain injury is of increasing importance in neuropsychological assessment. Lawyers involved in brain injury litigation cases routinely coach their clients how to approach neuropsychological testing to their advantage. Thus, it is important to know how robust assessment methods are with respect to symptom malingering or exaggeration. Methods The influence of different coaching methods on the simulated malingering of memory impairments is investigated in neurologically healthy participants using the Short-Term-Memory Test from the Bremer Symptom-Validierung (STM-BSV). Cut-offs were derived from patients with mild to severe traumatic brain injury. For comparison purposes, the German adaptation of the Rey Auditory Verbal Learning Test (AVLT), and the Rey 15 Items Test (FIT) were additionally administered. Four groups of neurologically healthy subjects were instructed to (1) perform as best as they can, (2) simulate brain injury, (3) simulate brain injury and received additional information about the sequelae of head trauma, (4) simulate brain injury and received additional information on how to avoid detection. Furthermore, a group of patients with mild to severe closed head injury performed the tests with best effort. Results The naïve simulator and the symptom coached groups were the easiest to detect, whereas the symptom plus test coached group was the hardest to detect. The AVLT and the FIT were not suited to detect simulators (sensitivities from 0% to 50.8% at 75% specificity) whereas the STM-BSV detected simulators with 67% – 88% sensitivity at a specificity of 73%. However, the STM-BSV was not robust to coaching. Conclusion The present investigation shows that symptom validity testing as implemented in the BSV-STM is one clinically useful element in the detection of memory malingering. However, clinicians have to be aware that coaching influences performance in the test.

Background: Chronic immune-mediated demyelinating polyneuropathy (CIP) represents a heterogeneous pool of motor, sensory, sensorimotor, symmetric, or asymmetric syndromes. Objective: To evaluate published diagnostic classifications and characterize predictors of treatment response. Methods: One hundred two of 158 patients with a working diagnosis of CIP were included and clinically characterized because they had electrophysiologic and/or histologic evidence of demyelination. The biostatistical profile of patients with symmetric clinical manifestation was analyzed using three proposed classifications (American Academy of Neurology [AAN] criteria, modified AAN criteria, European Federation of Neurological Societies/Peripheral Nerve Society [EFNS/PNS] criteria). Treatment responses to IV immunoglobulins (IVIg) and their positive predictors were investigated. Results: Sensitivities (0.52 [AAN] vs 0.83 [modified AAN] vs 0.95 [EFNS/PNS]) and negative predictive values (0.68 vs 0.85 vs 0.92) differed markedly, whereas specificities (0.94 vs 0.90 vs 0.96) and positive predictive values (0.89 vs 0.89 vs 0.97) were similar. In CIP patients treated with IVIg, a positive response was found in 62 of 76 (82%). Patients with a monophasic or relapsing–remitting course or a more than twofold CSF protein increase had the highest probability to respond to IVIg, most evident when using the modified AAN criteria. Conclusions: The European Federation of Neurological Societies/Peripheral Nerve Society criteria for chronic inflammatory demyelinating polyneuropathy improve treatment of patients with chronic immune-mediated demyelinating polyneuropathy, particularly with respect to diagnostic issues. To predict IV immunoglobulin treatment response, the modified American Academy of Neurology criteria are the most valuable classification provided an increased CSF protein level.

Defining tools in magnetic resonance imaging (MRI) representing specific pathological processes is needed to understand the complex relationship between inflammation, myelin breakdown, axonal injury and clinical symptoms in multiple sclerosis (MS) and its variants. Here, we describe a case of histologically-defined MS, in which the radiological appearance of the lesion and clinical course support the diagnosis of Balo's concentric sclerosis. Serial magnetization transfer, diffusion tensor imaging and 1H-magnetic resonance spectroscopy, from 14 days to 13 months after biopsy, allow the contextual interpretation of specific pathological changes. In our case, acute inflammation was sensitively traced by fractional anisotropy and increased lactate in spectroscopy. In contrast, magnetization transfer ratio and the apparent diffusion coefficient monitor the sequential loss of tissue in selected rings of the lesion. The delay from the peak of symptoms in a dramatic clinical course to the maximum tissue destruction indicated through MRI suggests that compromise of axonal function may be decisive for the acute clinical situation. This is the first report comparing 1Hmagnetic resonance spectroscopy, magnetization transfer and diffusion tensor imaging with histopathology in a patient with Balo's concentric sclerosis. Multiple Sclerosis 2007; 13: 471-482. http://msj.sagepub.com

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogenous disease of probably autoimmune origin. Recently published criteria give consideration to its clinical heterogeneity as well as to the impact of positive treatment response in making the diagnosis ex iuvantibus. Beyond intravenous immunoglobulins (IVIg), steroids, azathioprine, mycophenolate, ciclosporine, cyclophosphamide or plasma exchange are accepted as standard or escalating treatment options. Objective: To define the positive predictive value for treatment response of elevated cerebrospinal fluid (CSF) protein in CIDP patients. Patients and methods: CSF protein pre-treatment levels at time of diagnosis of 72 patients with positive EFNS criteria for CIDP were analysed retrospectively. CSF protein up to 420mg/l was assessed to be normal. For statistical analysis total positive rate (TPR); total negative rate (TNR), positive and negative preditive values (PPV, NPV), and finally likelihood ratios (LHR) were calculated to evaluate positive tretament prediction. Results: The LHR of patients with a more than than two-fold increase in CSF protein (i.e. >840mg/l) and IVIg application was 2.5 and their PPV 91% (TPR 0.55, TNR 0.78, NPV 0.29). Other immune therapies did not show higher LHR in these patients. Conclusion: The odds for a positive treatment response to IVIg is 2.5-fold higher in CIDP patients with CSF protein elevation >840mg/l than in patients with lower CSF values. Prospective data should be collected to prove the clinical validity and usefulness of CSF protein elevation as a predictive marker in CIDP.

Recently, several in vitro studies have demonstrated production of the potent immunosuppressive cytokine transforming growth factor beta (TGF-beta)2 in glioblastoma cell lines. Systematic studies of the concentration of TGF-beta isoforms in the plasma of patients harboring intracerebral tumors do not exist. In the present study, the concentrations of TGF-beta1 and TGF-beta2 in platelet-poor plasma of 21 patients with glioblastoma before and after extensive resection were measured by specific ELISA systems and related to survival. The plasma concentrations of latent TGF-beta1 of patients with glioblastoma prior to surgery were significantly higher in comparison to healthy control probands, but not to patients with multiple sclerosis (MS). Furthermore, latent TGF-beta2 was found to be significantly increased in the plasma of patients with glioblastoma in comparison to healthy control probands and patients with MS. After extensive resection of the tumor, the value of latent TGF-beta2 evidently decreased. Interestingly, the concentration of latent TGF-beta2 prior to surgery was correlated with survival and a strong relationship was found between the survival and the difference of latent TGF-beta2 levels prior to surgery minus the TGF-beta2 concentrations 7 days after surgery. A higher difference in these plasma concentrations >6 ng/ml vs.