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Zusammenfassung Die Multiple Sklerose (MS) führt häufig zu vorzeitiger Erwerbsunfähigkeit, allerdings sind die hierfür verantwortlichen Faktoren zumindest für Deutschland nur unzureichend bekannt, und oftmals werden relevante Symptome bei der Leistungsbeurteilung und der Rehabilitationsplanung nicht ausreichend beachtet. Daher identifizierten wir in einem zweiteiligen Forschungsprojekt zunächst die relevanten Einflussgrößen, die die berufliche Leistungsfähigkeit bei MS-Betroffenen determinieren, und entwickelten darauf basierend MS-spezifische Assessment-Instrumente. Im ersten Teil wurde nach einer literaturrecherche ein umfangreicher Fragebogen entwickelt, der u. a. standardisierte und validierte Instrumente zu Schwierigkeiten im Beruf (»Würzburger Screening für berufliche Problemlagen«, »MS Work Difficulties Questionnaire (MSWDQ)« und Fragen zur Symptombelastung beinhaltete. Damit wurden nach einem Vortest bei 20 MS-Patienten insgesamt 279 (189 erwerbstätige, 90 berentete) MS-Patienten befragt, die zu einer stationären Rehabilitationsmaßnahme im Neurologischen Rehabilitationszentrum Quellenhof aufgenommen worden waren. In beiden Gruppen beurteilten 81 % bzw. 74 % der Rehabilitanden ihre berufliche Tätigkeit als sehr wichtig. Als Prädiktoren für eine Erwerbstätigkeit erwiesen sich Alter, Krankheitsdauer, Behinderungsgrad (EDSS) und Bildungsniveau. Mithilfe einer Regressionsanalyse waren berufliche Schwierigkeiten (Würzburger Screening und MSWDQ) mit den Symptomen kognitive Störungen, depressive Verstimmung, Schmerzen, Mobilitätseinschränkungen bzw. Gangstörungen, Gleichgewichtsstörungen, Fatigue und Sehstörungen assoziiert. Im zweiten Teil wurden zu jedem dieser Symptome anhand einer erneuten Literaturrecherche standardisierte und validierte, patientenbasierte Assessment-Instrumente ausgewählt. Diese wurden zusammen mit dem Fragebogen des ersten Teils bei einer zweiten Stichprobe von weiteren 102 berufstätigen Rehabilitanden mit MS eingesetzt, von denen 76 (75 %) an der postalischen Nachbefragung 6 Monate nach Entlassung teilnahmen. Mithilfe einer erneuten Regressionsanalyse, den Summenwerten der Symptomskalen und dem Vergleich zwischen mittlerweile berenteten (n = 9) und weiterhin berufstätigen (n = 62) Patienten konnten die im vorherigen Teil erhobenen Befunde bestätigt werden. Damit steht nun ein Set von Assessment-Instrumenten zur Verfügung, mit dem bei MS-Betroffenen berufliche Problemlagen identifiziert und das berufliche Leistungsvermögen detailliert und standardisiert erfasst und zuverlässig beurteilt werden kann. Schlüsselwörter: Multiple Sklerose, Erwerbsfähigkeit, Rehabilitation, Assessment Abstract Multiple sclerosis (MS) is a common cause of unemployment, but the influencing factors are not well understood, at least in Germany, and disabling symptoms are often neglected. We therefore attempted (1) to identify relevant factors that predict employment, and (2) to develop assessment instruments specifically designed for work difficulties and symptoms that impact work ability. In the first part of the study, 279 MS patients admitted to inpatient neurological rehabilitation (189 employed, 90 unemployed) were evaluated with a comprehensive questionnaire that included standardized instruments dealing (among others) with work difficulties (“Würzburger Screening für berufliche Problemlagen”,“MS Work Difficulties Questionnaire [MSWDQ]”) and symptom burden. Most patients in both groups (81 % and 74 %) stated that working was very important for them. Age, disease duration, disability (EDSS) and education were predictive for employment. By means of regression analysis, work difficulties were associated with the following symptoms: cognitive dysfunction, depression, pain, mobility restrictions and gait disorders, balance problems, fatigue and visual disturbances. In the second part of the study, patient-oriented outcomes were identified for each of these symptoms and applied to another sample of 102 MS patients admitted to rehabilitation, of whom 76 (75 %) were evaluated at follow-up after 6 months. Regression analysis, sum scores of symptom scales and comparison between retired (n = 9) and still employed (n = 62) patients confirmed our previous results. With the findings of this study, a set of assessment instruments is available that may help to identify work difficulties and to properly evaluate the ability to work in patients with MS. Keywords: multiple sclerosis, employment, rehabilitation, assessment

Influence of fatigue and cognitive impairment on the use of health services, work performance and quality of life (utility): A study with 5,475 patients with multiple sclerosis in Germany Introduction: People with multiple sclerosis (MS) experience a number of neurological problems beyond the general outcome measures of relapses and disability that can independently affect costs and quality of life. Objectives: To investigate the effect of self-assessed fatigue and subjective cognitive impairment on direct healthcare consumption, work participation and utility in Germany. Methods: The study included 5,475 participants and investigated – in addition to all resource consumption – fatigue, cognitive impairment and the effect of MS while at work using visual analogue scales (VAS 0–10). The analysis controlled for gender, age, disease duration, education, disability, and use of disease-modifying treatments. Results: The level of fatigue and cognitive impairment was significantly and independently correlated with all resource utilisation, workforce participation and utility (p

Die symptomatische Behandlung der multiplen Sklerose (MS) hat heutzutage neben der Immuntherapie einen hohen Stellenwert im umfassenden Therapiekonzept dieser chronischen Erkrankung, tragt sie doch erheblich zu einer Verringerung von Beeintrachtigungen im Alltag, sozialen und beruflichen Leben sowie zur Verbesserung der Lebensqualitat bei. Seit der letzten umfassenden Bestandsaufnahme 2004 in dieser Zeitschrift sowie den Leitlinien der DGN (Deutsche Gesellschaft fur Neurologie)/KKN-MS (Klinisches Kompetenznetz Multiple Sklerose) zu Diagnose und Therapie der MS 2014 haben sich Neuerungen und Erganzungen in den Bereichen Mobilitat, Blasenfunktion, Sexualfunktionen, Augen, Fatigue, Kognition und Rehabilitation ergeben. Diese sowie weitere Aspekte (Messmethoden des jeweiligen Symptoms, Therapieziele, Gesamtbehandlungsplan) werden in einer Reihe aus 6 Einzelbeitragen vorgestellt. Hier soll auf die Symptomatik von Blasenfunktionsstorungen eingegangen werden.

Die symptomatische Behandlung der multiplen Sklerose (MS) hat heutzutage neben der Immuntherapie einen hohen Stellenwert im umfassenden Therapiekonzept dieser chronischen Erkrankung, tragt sie doch erheblich zu einer Verringerung von Beeintrachtigungen im Alltag, sozialen und beruflichen Leben sowie zur Verbesserung der Lebensqualitat bei. Seit der letzten umfassenden Bestandsaufnahme 2004 in dieser Zeitschrift sowie den Leitlinien der DGN(Deutschen Gesellschaft fur Neurologie)/KKN-MS(Klinisches Kompetenznetz Multiple Sklerose) zu Diagnose und Therapie der MS 2014 haben sich Neuerungen und Erganzungen in den Bereichen Mobilitat, Blasenfunktion, Sexualfunktionen, Augen, Fatigue, Kognition und Rehabilitation ergeben. Diese sowie weitere Aspekte (Messmethoden des jeweiligen Symptoms, Therapieziele, Gesamtbehandlungsplan) werden in einer Reihe aus 6 Einzelbeitragen vorgestellt. Hier soll auf die Fatigue eingegangen werden.

Die symptomatische Behandlung der multiplen Sklerose (MS) hat heutzutage neben der Immuntherapie einen hohen Stellenwert im umfassenden Therapiekonzept dieser chronischen Erkrankung, tragt sie doch erheblich zu einer Verringerung von Beeintrachtigungen im Alltag, sozialen und beruflichen Leben sowie zur Verbesserung der Lebensqualitat bei. Seit der letzten umfassenden Bestandsaufnahme 2004 in dieser Zeitschrift sowie den Leitlinien der Deutschen Gesellschaft fur Neurologie (DGN)/Klinisches Kompetenznetz Multiple Sklerose (KKN-MS) zu Diagnose und Therapie der MS 2014 haben sich Neuerungen und Erganzungen in den Bereichen Mobilitat, Blasenfunktion, Sexualfunktionen, Augen, Fatigue, Kognition und Rehabilitation ergeben. Diese sowie weitere Aspekte (Messmethoden des jeweiligen Symptoms, Therapieziele, Gesamtbehandlungsplan) werden in mehreren Einzelbeitragen vorgestellt. In diesem Abschnitt wird auf die kognitiven Storungen und die wachsende Bedeutung der Rehabilitation eingegangen.

Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992–1995 and 2005–2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force aEuroProvision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

ZusammenfassungNeben den vielfältigen körperlichen Symptomen der Multiplen Sklerose (MS) verdient die erhöhte Erschöpfbarkeit (Fatigue) besondere Beachtung, da sie mit zu den häufigsten Beschwerden zählt und die Leistungsfähigkeit in Alltag und Beruf teilweise erheblich einschränken kann. Die Pathogenese ist letztendlich unbekannt; wahrscheinlich handelt es sich um ein Syndrom mit verschiedenen Ursachen. Sekundäre Mechanismen wie Schlafstörungen, eine Anämie oder eine Schilddrüsenfunktionsstörung, aber auch Depressionen und kognitive Störungen müssen von der Fatigue im engeren Sinn (primäre Fatigue) abgegrenzt werden. Die subjektive Dimension der Fatigue kann mit standardisierten Fragebogen erfasst werden. Da sich zumindest ein Teil der Symptomatik mit einer Aufmerksamkeitsstörung erklärt lässt, kann mittlerweile die Fatigue mit einer Aufmerksamkeitstestung (Subtest „Alertness” aus der Testbatterie zur Aufmerksamkeitsprüfung) objektiviert werden. Die medikamentöse Therapie mit z. B. Amantadin oder Modafinil stellt in Einzelfällen eine Option dar, ist aber oftmals nicht bzw. nicht anhaltend erfolgreich. Daher besteht das Behandlungskonzept vor allem aus nicht medikamentösen Maßnahmen wie Beratung von Patienten und Angehörigen, Strukturierung des Tagesablaufs mit der Möglichkeit zu ausreichenden Pausen, Vermittlung von

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKNMS) in 2014, several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in several individual contributions. In this article the symptoms of sexual dysfunction and eye movement disorders are discussed.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKNMS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of bladder dysfunction will be discussed.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in a series of 6 individual contributions. In this article the symptom of fatigue is discussed.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis ("Klinisches Kompetenznetz Multiple Sklerose", KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in several individual contributions. In this article the symptoms of cognitive disorders and the growing impact of rehabilitation are discussed.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN‑MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of gait disorders and spasticity will be discussed.

With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force "Provision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 ± 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS. Multiple Sclerosis 2008; 14: 219—230. http://msj.sagepub.com

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

The impact of spasticity induced by multiple sclerosis (MS) on patients and the applied treatment options have so far been insufficiently studied.This was a multicentre, retrospective, nationwide study of the care situation of MS spasticity in Germany from the perspective of both patients and physicians.In this study 414 patients (mean age 48.6 years, 64.3 % women) from 42 centres were analyzed: 27 % suffered from mild, 44 % from moderate and 29 % from severe spasticity. The most common comorbidities were depression and anxiety (25.6 %) and 94.9 % suffered from concomitant symptoms (e.g. fatigue and bladder disorders). The severity of spasticity and its consequences were assessed by both patients and physicians and 54.8 % of physicians were dissatisfied with available treatment options. The most frequently cited disadvantages of currently available antispastic treatment were adverse effects (95.2 %) und insufficient effectiveness (88.1 %) and one third of patients sought help by self-medication.This initial assessment of MS-induced spasticity in Germany showed that patients experienced severe impairment due to spasticity. Available treatment options were assessed as dissatisfying.

The existing health-related quality of life questionnaires on multiple sclerosis (MS) only partially reflect the patient's point of view on the reduction of activities of daily living. Their development and validation was not performed in different languages. That is what prompted the development of the Multiple Sclerosis International Quality of Life (MusiQoL) Questionnaire as an international multidimensional measurement instrument. This paper presents this new development and the results of the German subgroup versus the total international sample.A total of 1,992 MS patients from 15 countries, including 209 German patients, took part in the study between January 2004 and February 2005. The patients took the MusiQoL survey at baseline and at 21±7 days as well as completing a symptom-related checklist and the SF-36 short form survey. Demographics, history and MS classification data were also generated. Reproducibility, sensitivity, convergent and discriminant validity were analysed.Convergent and discriminant validity and reproducibility were satisfactory for all dimensions of the MusiQoL. The dimensional scores correlated moderately but significantly with the SF-36 scores, but showed a discriminant validity in terms of gender, socioeconomic status and health status that was more pronounced in the overall population than in the German subpopulation. The highest correlations were observed between the MusiQoL dimension of activities of daily living and the Expanded Disability Status Scale (EDSS).The results of this study confirm the validity and reliability of MusiQoL as an instrument for measuring the quality of life of German and international MS patients.

Im Jahre 2001 initiierte die DMSG Bundesverband e.V. die Einrichtung eines Multiple Sklerose (MS) Registers fur Deutschland, um Informationen uber die Versorgungssituation von MS-Patienten zu erhalten. Zum 28.02.2009 nahmen insgesamt 112 Zentren verschiedener Versorgungsbereiche an der Dokumentation teil, davon sind 53 Akutkliniken, 18 Schwerpunktpraxen und 16 Rehabilitationskliniken. Ziel der vorliegenden Auswertung war ein Vergleich der Basisdaten der aus den drei Versorgungsbereichen stammenden Patientenpopulation, um Unterschiede zwischen diesen drei Bereichen zu determinieren.

Der Bundesverband der Deutschen Multiple Sklerose Gesellschaft e.V. (DMSG) initiierte 2001 die Einrichtung eines Multiple Sklerose (MS) Registers fur Deutschland. Ziel des Registers ist die flachendeckende Erfassung von Daten zu klinischen Charakteristika der MS, soziodemographischen Aspekten und zur Versorgungssituation der MSErkrankten in Deutschland. Nach Abschluss der Pilotphase werden seit 2005 kontinuierlich weitere Dokumentationszentren rekrutiert.

Unter Federfuhrung der DMSG, Bundesverband e.V. wurde 2001 die Einrichtung eines flachendeckenden MS-Registers initiiert, um epidemiologische Daten zur Anzahl der an multipler Sklerose (MS) Erkrankten, deren Verlaufsformen und die Versorgungssituation in Deutschland zu gewinnen. Wahrend der zweijahrigen Pilotphase wurden in 5 Zentren 3.223 Patienten standardisiert dokumentiert (Flachenecker et al, Nervenarzt 2005;76:967-975). Im Anschluss wurde der Basisdatensatz modifiziert und neue Zentren rekrutiert.

Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). Several fatigue scales have been developed, but rigorous psychometric methods have not always been applied and validation was mainly based on small numbers of patients. We therefore assembled a new fatigue scale from a set of widely used scales and assessed its psychometric properties in a large sample of MS patients.Fatigue was assessed in 158 MS patients by four published quantitative scales: the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MS-specific Fatigue Severity Scale (MFSS), and Visual Analogue Scale. From these a new fatigue scale, the Würzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS), was assembled. It contains 17 items with values from 0 to 4. The WEIMuS scale was validated in a subgroup of 67 patients and a control group of 68 patients.The MFIS and FSS but not the MFSS showed high internal consistency and split-half reliability. After applying factor analysis within the scales, fairly reliable and valid items originally found in the MFIS and FSS were selected to construct the final 17-item WEIMuS scale, which showed a high degree of reliability. In the validation study, varimax rotated factor analysis extracted two main factors corresponding to both cognitive and physical fatigue.The new, two-dimensional WEIMuS showed good psychometric properties, is easy to use, and may therefore be a useful tool for the assessment of MS-associated fatigue. Multiple sclerosis patients suffer from different types of fatigue which could be attributed to cognitive and physical fatigue. Thus, MS-associated fatigue is different from common tiredness.

In the summer of 2001, a nationwide epidemiological multiple sclerosis (MS) register was initiated under the auspices of the German MS Society (DMSG). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. During the 2-year pilot phase, five MS centers with various regional differences and treatment methods participated, leading to a representative selection of patients. In December 2003, standardised data sets of 3,458 MS patients were available for evaluation. After examining the quality of the data, 3,223 sets remained for further analysis. The demographics were similar to those obtained from other epidemiological studies: 72% of the patients were female, mean age was 42.9+/-11.2 years, mean disease duration 12.6+/-8.7 years, and 64% suffered from the relapsing-remitting form of the disease. The median EDSS was 3.0, and 69% of patients had an EDSS/=4.0. The great effect of this disorder was underscored by the fact that one third of the patients had prematurely retired due to MS. After successful completion of the pilot phase, the MS register will provide reliable data and thus serve as an important tool to improve the overall situation of MS patients in Germany.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Superficial siderosis of the central nervous system (CNS) is a rare chronic progressive disorder caused by chronic subarachnoid hemorrhage. We present four patients with superficial siderosis of the CNS to describe the characteristic symptoms, and to discuss the pathogenetic heterogeneity and possible new therapeutic approaches.The causes of chronic subarachnoid bleeding in superficial siderosis were different. In two patients surgical treatment of ependymoma or cerebral cavernomas were the underlying diseases. No cause was detected in one patient. For the first time, we present one patient with vasculitis of the central nervous system associated with systemic hemochromatosis in superficial siderosis. Therapeutic approaches included exstirpation of cavernomas as the source of chronic bleeding in one patient, immunosuppressive therapy and venupunctures in the patient with vasculitis and hemochromatosis, and symptomatic treatment with chelating agents and antioxidants. The patients remained clinically stable for the follow-up period of up to 2 years.Our cases underline the pathogenetic heterogeneity of superficial siderosis and favor the early diagnosis for prompt initiation of therapy. Besides treatment of the underlying condition, antioxidants and radical scavengers may be effective in halting the progression of the disease.

Several lines of evidence suggest that catecholamines, especially norepinephrine, are implicated in the etiology and/or symptomatology of panic disorder (PD). At the cellular level, functional noradrenergic neurotransmission depends on synaptic reuptake of norepinephrine as mediated by the norepinephrine transporter (NET). A pharmacological target of agents with an established anti-panic efficacy, e.g. tricyclic antidepressants, the NET is of particular interest in PD. We investigated the NET gene for the presence of 6 naturally occurring exonic sequence variants, 5 of which give rise to amino acid substitutions (Val69Ile, Thr99Ile, Val245Ile, Val449Ile and Gly478Ser) in a population of 87 patients with PD and 89 healthy controls. Except for a silent substitution (G1287A), overall frequencies of variant alleles were low (≤0.016). None of the variants under study was found to be associated with PD regardless of an additional diagnosis of agoraphobia.

Autonomic neuropathy is an important complication of Guillain-Barré syndrome (GBS). In particular, over-reactivity of vagal function may lead to serious cardiac disturbances ranging from bradycardia to asystole. Early recognition of these events is essential for appropriate intervention such as the insertion of a cardiac pacemaker. Recent studies indicate that serious bradyarrhythmias could be observed in severely and even less severely affected patients who were still able to walk more than 5 meters. Conventional measures such as the presence of tachycardia, heart rate and blood pressure fluctuations, or short-term heart rate variability and standardized autonomic function tests were not useful in predicting serious bradyarrhythmias. However, abnormal sensitivity to eyeball pressure testing correctly identified two of three patients who needed cardiac pacing or cardiopulmonary resuscitation due to heart arrest; eight of ten patients without bradyarrhythmic events showed normal responses. New methods such as the 24-hour heart rate power spectrum may yield sensitive and specific markers for assessing the risk of impending and potentially life-threatening arrhythmias in patients with GBS.

Die vegetative Dysfunktion bei der multiplen Sklerose (MS) umfasst nicht nur Blasen-, Mastdarm- und Sexualstorungen, sondern kann sich auch in anderen autonomen Funktionssystemen niederschlagen. Hierzu gehoren die Storungen der Herz-Kreislauf-Regulation, die — da sie ublicherweise im klinischen Alltag hinter den motorischen, zerebellaren und sensiblen Ausfallen zuruckstehen — selten beachtet und meistens nicht naher untersucht werden. Gleichwohl konnen Einschrankungen in diesem Funktionssystem auch zu belastenden Symptomen wie einer ausgepragten orthostatischen Intoleranz bis hin zu Synkopen oder kardialen Arrhythmien fuhren und sind im Verlauf der MS nicht selten anzutreffen, konnen andererseits aber auch prasentierendes Symptom sein. Daneben haben autonome Funktionsstorungen und insbesondere eine verminderte Aktivitat des sympathischen Nervensystems moglicherweise auch Bedeutung fur die Atiopathogenese der MS, da es vielfaltige Wechselwirkungen zwischen dem sympathischem Nervensystem und dem Immunsystem gibt.

The diagnosis of multiple sclerosis is primarily based on clinical criteria considering the dissemination of neurological symptoms in time and space. Laboratory tests (magnetic resonance imaging, examination of cerebrospinal fluid, and evoked potentials) are important to confirm the diagnosis and assess disease activity. With the improvement of these methods, MS could be diagnosed at a very early stage of the disease allowing for the prompt initiation of immunotherapies. An early diagnosis and prediction of the future course of MS are also important for adequate counselling of the predominantly young patients about their professional plans. However, in the early stages of MS, prediction of disability remains difficult even if the patient is definitely diagnosed to suffer from MS.

Mitoxantrone is an anthracenedione anti-neoplastic agent that has recently been shown to be effective in ameliorating disease activity in multiple sclerosis (MS) as indicated by clinical and MRI data. However, the role of mitoxantrone in escalating treatment of patients with frequent and severe relapses and with rapid progression of disability is less clear. In this retrospective analysis we report on 15 patients with severe relapsing-remitting (9 patients) and secondary progressive MS with superimposed exacerbations (6 patients) treated open-labeled with mitoxantrone in our Clinical Research Group from July 1994 to October 1998. Eleven of these patients (73%) were treated with azathioprine, interferon-beta-1b or cyclophosphamide before. The patients received mitoxantrone over a period of at least 12 months (19 +/- 6 months) with a single dose of 10 mg/m2 monthly for the first three months. Thereafter, infusions were repeated every 3 months (total dose 141 mg +/- 45 mg). The annual relapse rate could be significantly reduced from 3.0 +/- 1.5 in the year before therapy to 0.5 +/- 0.5 during therapy. Nine patients (60%) were stabilised, while four patients (27%) showed an improvement of disability. The treatment was well tolerated with only minor side effects. These results although retrospectively obtained confirm previous trials showing that mitoxantrone may be useful in MS patients with frequent and severe exacerbations and/or a rapidly progressive course of the disease who have had other immunomodulatory medication.

To study the temporal course and the relationship between autonomic failure and motor weakness in Guillain-Barré syndrome (GBS), a total of 164 autonomic function tests were serially applied for up to 1 year in 13 consecutive patients. Results were compared with those obtained in 25 healthy volunteers and 13 patients with other neurological diseases. Parasympathetic function tests comprised heart rate responses to Valsalva maneuver, deep breathing, and active change of posture, whereas sympathetic vasomotor function was assessed by blood pressure responses to handgrip and standing. At the height of the disease, subclinical autonomic involvement of both parasympathetic and sympathetic arms was revealed in the vast majority of patients. Abnormalities of autonomic function tests improved gradually over time, paralleling the recovery of motor function, but were only partially related to clinically significant autonomic dysfunction. Correlation analysis suggested that tachycardia in the context of GBS might be caused by a reduction of sympathetically mediated peripheral vascular tone rather than by vagal failure.

The second part of this review summarizes the predictive value of demographic factors, the early clinical course and paraclinical methods in the prognosis of multiple sclerosis (MS). The chronic progressive course is generally thought to be associated with a worse outcome compared to relapsing-remitting MS. Moderate disability within 5 years, residual pyramidal and cerebellar deficits 6 months following an acute attack, motor, cerebellar and possibly brain stem exacerbations as well as frequent relapses were found to indicate an increased risk for developing severe disability or increased mortality. Magnetic resonance imaging (MRI), evoked potentials and cerebrospinal fluid findings were not found to be predictive in clinically definite MS, although there was a weak association of MRI findings and disability. However, these paraclinical modalities were important methods to predict the further development of clinically isolated demyelinating syndromes. In this regard, MRI was identified as the strongest predictive factor of the conversion to definite MS.

EDMUS, the European Database for Multiple Sclerosis (MS), was established on the occasion of the first European Concerted Action for MS under the auspices of the European Community. The system is user-friendly and makes it possible to record and retrieve data relevant to MS. Within the framework of another European Concerted Action, several international multicenter trials are currently in progress. EVALUED, a validation of the EDMUS system, assesses the interrater variability; PRIMS examines the influence of pregnancy and the post-partum period on the course of MS; and PRESTIMUS investigates predictive factors in suspected MS. Further, planned studies include ERAZMUS (early azathioprine and interferon-beta treatment in MS) and AZASTOP, which is designed to evaluate the effect of stopping azathioprine treatment.

This work summarizes the design and state of recruitment of the European multicentre prospective PRIMS (PRegnancy In Multiple Sclerosis) project on the relationship between pregnancy and multiple sclerosis. Relapse rate, long-term effects, influence of delivery and breastfeeding as well as immunomodulation during pregnancy and puerperium are reviewed. The results suggest an increase in relapse rate during the first 3 months of puerperium with an equal or lessened risk during the 9 months of pregnancy. Overall, long-term disability seems not to be increased. The mode of delivery or breast-feeding has no adverse effects on the course of the disease. Immunological phenomena during pregnancy do not correlate to the altered course of MS.