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Multiple sclerosis and physical activity: A German-wide survey on the behaviour, barriers and desires of those affected Background: Physical activity (PA) has beneficial effects on many disease related symptoms in people with multiple sclerosis (pwMS). Physical parameters – such as muscle strength, endurance, and balance – as well as fatigue, depression and neurocognitive functioning, can be positively influenced by regular PA. Nevertheless, pwMS are less physically active than the general population. The reasons for this are not well understood. Hypothesis: We hypothesized that beside personal factors, environmental factors such as transport and access to exercise facilities probably are responsible for the widespread physical inactivity among people with MS. The perception of environmental barriers could be influenced by the place of residence (city/rural area) or the degree of physical impairment. Methods: Between April and October 2017 we examined the perception of PA and exercise options among pwMS from different regions in Germany. Using an online survey, we collected data from 630 pwMS. Results: Our data indicate that pwMS in rural areas gave lower ratings for their PA and exercise options than those in cities (p

Die Einfuhrung biologischer und zielgerichteter synthetischer („targeted-synthetic“) krankheitsmodifizierender Basistherapeutika hat zu mehr Spezifitat in der Behandlung von Autoimmunerkrankungen gefuhrt. Sie erfordern allerdings eine kontinuierliche oder intermittierende Verabreichung, sind mit kumulativen Risiken fur Nebenwirkungen verbunden, verursachen hohe Kosten und bieten keine Heilung. Im Gegensatz dazu kann eine hoch dosierte Chemotherapie mit anschliesender Transplantation autologer hamatopoetischer Stammzellen (AHSZT) lang anhaltende und therapiefreie Remissionen bei verschiedenen Autoimmunerkrankungen induzieren. Das Prinzip der AHSZT beruht auf einer Eliminierung wichtiger Komponenten des autoreaktiven immunologischen Gedachtnisses mit anschliesender Neubildung des gesamten Immunsystems. Dieser sog. „Immun-Reset“ ist mit fundamentalen Veranderungen des Immunrepertoires verbunden, die zu einer Toleranzinduktion gegenuber Selbst fuhren. In diesem Beitrag prasentieren wir aktuelle Indikationen der AHSZT fur Autoimmunerkrankungen, basierend auf Registerdaten der Europaischen Gesellschaft fur Blut- und Knochenmarktransplantation (EBMT), und diskutieren Ergebnisse aus mechanistischen Studien, die detaillierte Einblicke in die Wirkungsweise der Therapie bieten.

The SLCMSR was formed as an international Multiple Sclerosis Trials, Research and Resource Center to identify clinical MRI and other predictors of the course of multiple sclerosis (MS) based on a large database of natural history and clinical trial data. Using an elaborate validation concept several key findings were published, challenging established outcome parameters and their assessment in MS such as disability ratings with Expanded Disability Status Scale (EDSS), relapses and MRI endpoints. Sustained increase of EDSS appeared to be an invalid outcome for 2-3 year clinical trials at least in patients with relapsing-remitting MS. The number of gadolinium-enhancing lesions and T2-lesion load on MRI were shown not to have a meaningful additional predictive value for the disease course. These issues risen some 15 years ago had triggered controversial discussions which have also been noticed by regulatory authorities and they all have not been resolved. In addition the SLCMSR contributed to the development of new outcomes such as real-world walking speed as an attractive, ecologically valid tool based on a wearable device. A so-called evidence-based-decision-support tool was constructed to provide individual prognostic estimates based on a matching algorithm to a given database. This paper condensates the findings of 20 years of critical MS research.

ObjectiveTo assess the impact of APOE polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS).MethodsThis multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nucleotide polymorphisms rs429358 (ε4) and rs7412 (ε2) of the APOE haplotype were assessed by allelic discrimination assays. Cognitive performance was evaluated using the 3-second paced auditory serial addition test and the Multiple Sclerosis Inventory Cognition (MUSIC). Sum scores were calculated to approximate the overall cognitive performance and memory-centered cognitive functions. The impact of the APOE carrier status on cognitive performance was assessed using multiple linear regression models, also including demographic, clinical, MRI, and lifestyle factors.ResultsAPOE ε4 homozygosity was associated with lower overall cognitive performance, whereas no relevant association was observed for APOE ε4 heterozygosity or APOE ε2 carrier status. Furthermore, higher disability levels, MRI lesion load, and depressive symptoms were associated with lower cognitive performance. Patients consuming alcohol had higher test scores than patients not consuming alcohol. Female sex, lower disability, and alcohol consumption were associated with better performance in the memory-centered subtests of MUSIC, whereas no relevant association was observed for APOE carrier status.ConclusionAlong with parameters of a higher disease burden, APOE ε4 homozygosity was identified as a potential predictor of cognitive performance in this large cohort of patients with CIS and early RRMS.

The recent introduction of biologic and targeted synthetic disease-modifying drugs has led to more specificity in the treatment of autoimmune diseases; however, they require continuous or intermittent administration, are associated with cumulative risks for side effects, result in high costs and provide no cure. In contrast, high-dose chemotherapy followed by transplantation of autologous hematopoietic stem cells (AHSCT) has been demonstrated to induce clinical remission in various autoimmune diseases that can persist over many years without continued maintenance therapy. The principle behind AHSCT is an elimination of important components of the autoreactive immunological memory with subsequent regeneration of the complete immune system. Several studies have indicated that such an immune reset is associated with fundamental changes in the immune repertoire leading to an induction of tolerance against self-antigens. This article presents the current indications of AHSCT for autoimmune diseases based on the registry data of the European Society of Blood and Marrow Transplantation (EBMT) and discusses the results from mechanistic studies, which provide detailed insights into the mode of action of this treatment.

Multiple sclerosis treatment options are increasing. Evidence-based patient information (EBPI) are therefore crucial to enable patient involvement in decision making. Based on earlier work on decision support, patient information handbooks on 8 MS immunotherapies were developed, piloted and evaluated with support from the German Clinical Competence Network MS and the German MS Society.Handbooks were structured according to EBPI concepts. Drafts were commented by patient representatives and neurologists with an MS expertise. Executive boards of the German MS Society and the Competence Network as well as pharmaceutical companies' feedback was included. Handbooks were distributed among MS neurologists by the German MS Society. Evaluation followed applying a mixed methods approach with interviews, focus groups and surveys. One survey addressed persons with MS (pwMS) based on a questionnaire included in each handbook. Neurologists who received printed patient handbooks were invited to give feedback in a second survey.Eight handbooks were developed providing absolute and relative risk information in numbers and figures as well as monitoring needs and drug fact boxes. Despite the high amount of information and the display of low absolute risk reduction rates of treatments, handbooks were overall appreciated by pwMS (n=107) and mostly also by physicians (n=24). For more than 70% of the pwMS the information was new, understandable and supportive for decision making. But patients felt uncomfortable with relative risk information. However, response rates in the evaluation were low, exposing the challenges when implementing EBPI into clinical care. Therefore, conclusions must be considered preliminary.EBPI on immunotherapies for MS seem feasible and are appreciated by patients and treating neurologists but more implementation research is needed.

Background In neurological diseases presenting with a plethora of symptoms, the value of bodily functions for a given patient might be a guide for clinical management. Multiple sclerosis (MS) is paradigmatic in this respect, and little is known about the value of different bodily functions of patients and their physicians' perceptions. Methods In a multicenter study, 171 patients with relapsing-remitting multiple sclerosis (RRMS), 61% with a clinically active disease within the last 2 years were followed over up to 3 years and yearly patients and their study physician rated on the perceived value of 13 bodily functions via a priority list. Differences between patients and physicians as well as modulating disease demographic factors were analyzed. Results Patients with RRMS rated visual function followed by thinking and memory and walking highest while physicians stressed mobility, followed by thinking and memory and alertness most. Ratings were independent from disease duration or disability. Strongest value judgment differences were seen in swallowing regarded more relevant by patients and hand function regarded more relevant by physicians. In general, patients' and physicians' ratings through time were quite stable. Collapsing physical items into a physical functioning scale and mental items in a mental function scale, both dimensions were regarded equally important by patients while physicians underscored physical functioning (P = .016). Conclusion There are differences between patients and physicians in value statements of bodily functions in MS. In particular, visual functioning is under-recognized by physicians.

ObjectiveTo assess clinical characteristics, distribution of disease-modifying treatments (DMTs), and neuropsychological symptoms in a large cohort of patients with early-stage MS.MethodsThe German National MS Cohort is a multicenter prospective longitudinal cohort study that has recruited DMT-naive patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) since 2010. We evaluated their baseline characteristics and the prevalence of neuropsychological symptoms.ResultsOf 1,124 patients, with a 2.2:1 female-to-male ratio and median age at onset of 31.71 years (interquartile range [IQR]: 26.06–40.33), 44.6% and 55.3% had CIS and RRMS, respectively. The median Expanded Disability Status Scale (EDSS) score at baseline was 1.5 (IQR: 1.0–2.0). A proportion of 67.8% of patients started DMT after a median time of 167.0 days (IQR 90.0–377.5) since the first manifestation. A total of 64.7% and 70.4% of the 762 patients receiving early DMT were classified as CIS and RRMS, respectively. Fatigue, depressive symptoms, and cognitive dysfunction were detected in 36.5%, 33.5%, and 14.7% of patients, respectively.ConclusionBaseline characteristics of this large cohort of patients with early, untreated MS corroborated with other cohorts. Most patients received early DMT within the first year after disease onset, irrespective of a CIS or RRMS diagnosis. Despite the low EDSS score, neuropsychological symptoms affected a relevant proportion of patients.

Schwere intrathorakale Verletzungen sind selten, jedoch meist akut lebensbedrohlich. Sie treten haufig im Rahmen eines Polytraumas auf. Sind die polytraumatisierten Patienten stabilisiert, ist die Bildgebung essenzielle Grundlage der richtigen Versorgung und einer nachfolgenden Operation. Dabei kann die richtige Einschatzung der intrathorakalen Verletzungen nur interdisziplinar in enger Kooperation zwischen der Anasthesie, Unfall- und Thoraxchirurgie erfolgen. Je nach Verletzungsmuster mussen weitere Fachabteilungen hinzugezogen werden. Der vorliegende Artikel gibt einen Uberblick uber das Management der wichtigsten intrathorakalen Verletzungen.

Autologous hematopoietic stem cell transplantation (aHSCT) is still not the standard treatment for highly inflammatory multiple sclerosis (MS). Even though randomized controlled trials are lacking, predictors for treatment response have been established. Since 2007, ten patients have received aHSCT in Hamburg.To present observational data from patients treated in Hamburg and a review of the literature.Descriptive statistics were used for evaluating the course of the expanded disability status scale (EDSS) as a measure for clinical outcome, magnetic resonance imaging (MRI) and neuropsychology. New gadolinium and T2-MRI uptake lesions per scan were compared. In addition, a systematic review of the currently available literature was performed.The Hamburg series can be divided in two groups, one group including four patients with chronic progressive MS with low inflammatory activity (median EDSS = 6.25, 0.5 relapses per year, no gadolinium-enhancing lesions) and the other group including six patients with mild to moderate disability, relapses and inflammatory activity (median EDSS = 4.25, 1 relapse per year, 2 gadolinium-enhancing lesions). The median follow-up was 2.4 years. While the first group did not seem to benefit from aHSCT, an improvement in five out of six patients was observed in the second group. New T2 lesions occurred within the first 6 months but gadolinium-enhancing lesions were not observed (p 0.05). A systematic literature search identified a higher efficacy of aHSCT in younger, less disabled MS patients with inflammatory activity, similar to the findings from Hamburg.Cohort reports describe aHSCT as a safe and efficient treatment option in highly inflammatory MS. Based on these data aHSCT seems to be a reasonable option in selected patients with highly inflammatory MS but a randomized controlled trial is warranted.

Der Beteiligung von Patienten an medizinischen Entscheidungen kommt eine wachsende Bedeutung zu. Das Modell des Shared Decision Making (SDM) ist ein viel versprechendes Konzept der medizinischen Entscheidungsfindung, das versucht, eine Brucke zwischen patientenzentrierter und evidenzbasierter Medizin zu schlagen. Der vorliegende Beitrag stellt das Modell des SDM vor, gibt eine Ubersicht zur Studienlage und diskutiert die Implikationen von SDM fur den nervenarztlichen Fachbereich vor dem Hintergrund krankheitsspezifischer Besonderheiten.

Epidemiologische Untersuchungen haben in den letzten Jahren zunehmend Zusammenhange zwischen korperlicher Inaktivitat und der Entwicklung einer Reihe chronischer Erkrankungen aufgezeigt. Wurden bei Herz-Kreislauf-Erkrankungen schon seit den 70er-Jahren Trainingsprogramme etabliert, so schien noch bis vor kurzem eine korperliche Belastung bei schweren somatischen Erkrankungen wie Brustkrebs oder multipler Sklerose kontraindiziert. Mittlerweile finden sich immer mehr Untersuchungen, die aber auch hier positive psychische so wie somatische Effekte eines Fitnesstrainings zeigen. Diese Studien werden im vorliegenden Beitrag zusammenfassend dargestellt und um eigene Befunde erganzt. Bei Patientinnen mit Brustkrebs konnten wir anhaltende psychosoziale Therapie effekte auch noch ein Jahr nach Beendigung eines Therapieprogramms zeigen. Bei Patienten mit multipler Sklerose konnten wir die Induktion von Nerven wachstumsfaktoren unter Fitnesstraining nachweisen. Hier zu korrespondierend finden sich weitere Untersuchungen, die positive Effekte regelmasiger korperlicher Aktivitat auf Hirnleistungen, insbesondere bei alteren Menschen, beobachten. Bewegungstherapeutische Masnahmen konnten somit ein Schlusselpraventions- und Therapiekonzept fur die in einer alternden Gesellschaft zunehmend relevanten kognitiven Abbauprozesse werden.

Im Rahmen des Forderschwerpunktes des Bundesministeriums fur Gesundheit und soziale Sicherung „Der Patient als Partner im medizinischen Entscheidungsprozess“ untersuchen derzeit 10 Projekte bei jeweils unterschiedlichen Indikationen den Ansatz der Partizipativen Entscheidungsfindung. Die Gruppen stellten Instrumente zur Messung der Partizipativen Entscheidungsfindung zusammen, die von allen Projekten indikationsubergreifend eingesetzt werden. Da diese Instrumente nicht im deutschen Sprachraum entwickelt und validiert wurden, wurde uberpruft, inwiefern sie sich fur eine Anwendung im deutschen Gesundheitswesen eignen. Ergebnisse von Patienteninterviews und der indikationsubergreifenden Datenanalyse machten deutlich, dass eine Verbesserung der vorliegenden Messinstrumente zur Erfassung des Prozesses und der Effekte der Partizipativen Entscheidungsfindung notwendig ist. Aus diesem Grund entwickelten die beteiligten Projektgruppen im Rahmen der Arbeitsgruppe „Methoden“ ein neues Messinstrument. Es wurde ein theoriegeleitetes Vorgehen gewahlt, bei dem zunachst das Konstrukt der Partizipativen Entscheidungsfindung definiert wurde. Anschliesend wurden die relevanten Prozessschritte, die eine Partizipative Entscheidungsfindung kennzeichnen, erarbeitet. Diese Prozessschritte bildeten die Grundlage fur eine Operationalisierung von Fragen auf Einzelitemebene. Der neu entwickelte Fragebogen wird in der zweiten Projektphase des Forderschwerpunktes im Hinblick auf Testgutekriterien untersucht und bezuglich einer indikationsubergreifenden Anwendbarkeit validiert.

In many neurological diseases a depressive syndrome is a characteristic sign of the primary disease or is an important comorbidity. Post-stroke depression, for example, is a common and relevant complication following ischemic brain infarction. Approximately 4 out of every 10 stroke patients develop depressive disorders in the course of the disease which have a disadvantageous effect on the course and the prognosis. On the other hand depression is also a risk factor for certain neurological diseases as was recently demonstrated in a meta-analysis of prospective cohort studies which revealed a much higher stroke risk for depressive patients. Furthermore, depression plays an important role in other neurological diseases with respect to the course and quality of life, such as Parkinson's disease, multiple sclerosis and epilepsy. This article gives a review of the most important epidemiological, pathophysiological and therapeutic aspects of depressive disorders as a comorbidity of neurological diseases and as a risk factor for neurological diseases.

Severe intrathoracic injuries are uncommon but immediately life-threatening. These injuries are mostly associated with polytrauma. After stabilization of polytraumatized patients imaging is a prerequisite for treatment and operation planning. The assessment warrants an interdisciplinary approach primarily between the specialties of anesthesia, trauma surgery and thoracic surgery and further specialties should be involved depending on the injury pattern. This article gives an overview about the current management of the most important intrathoracic injuries.

Until now, the significance of plasma exchange (PE) as a treatment for steroid-unresponsive optic neuritis (ON) is still unclear because placebo-controlled and larger studies are missing. We report our experience with 23 patients treated by PE due to steroid-unresponsive ON.Patients were admitted to the University Medical Center Hamburg-Eppendorf between 2006 and 2010 with a visual acuity of50% on the affected eye following steroid treatment. Ten patients suffered from RR-MS, one from neuromyelitis optica, and 12 patients developed ON as a clinically isolated syndrome. Routinely, they were treated with five cycles of PE. Visual acuity was measured before and directly after PE and during follow-up (first follow-up after 50 days, second follow-up after 174 days).Altogether, 70% of our patients improved after PE, 69% of them showed a good or very good response to therapy. Patients who improved well after PE (n = 11) showed a mean visual acuity of 16% before PE compared to 45% immediately after PE and 60% at the first follow-up. No serious adverse events occurred.To our knowledge, our study is the largest case series of patients with steroid-unresponsive ON treated with PE. Based on our experience, we conclude that PE is an important treatment option for patients with steroid-unresponsive ON although placebo-controlled studies are missing until now.

New diagnostic criteria for multiple sclerosis (MS) have been recently proposed and further updates are upcoming. This systematic literature review summarizes diagnostic studies in suspected MS to clarify the value of diagnostic tests. We included studies of at least 40 patients followed up for 2 years. All studies are limited by the fact that no gold standard to validate diagnostic tests is available. A second relapse is used as a surrogate in relapsing-remitting MS, but long follow-up of at least 5 years is necessary to detect all cases. Many studies showed selection bias, partly because of the vague definition of a clinically isolated syndrome. Based on these limitations, sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%. Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%. Combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%). Studies on evoked potentials did not justify conclusions about their value. A combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis. However, the value of a very early diagnosis stays questionable as patients' benefit of new diagnostic criteria has never been addressed.

Die vorliegende Arbeit gibt einen Uberblick uber die Untersuchung von Immunparametern bei den funktionellen Kopfschmerzsyndromen Migrane und Clusterkopfschmerz. Bei allen methodischen Problemen dieser Studien sind immunologische Veranderungen reproduzierbar gezeigt worden. Dies sind vor allem das gehaufte Auftreten von Auto-Antikorpern bei Migrane, die vermehrten NK-Zell- und Monozytenzahlen in der Clusterattacke sowie Veranderungen in verschiedenen Mediatorsystemen (Prostaglandine, Zytokine und Neurotransmitter). Eine Einordnung in den pathogenetischen Zusammenhang der KS-Syndrome ist hingegen kaum moglich. Vor dem Hintergrund der zahlreichen neuroimmunologischen Verbindungen scheinen immunologische Veranderungen am ehesten Ausdruck des akuten oder chronischen Schmerzzustandes zu sein. Es ist von einem neuroimmunologischen Netzwerk auszugehen, bei dem Veranderungen in einem System immer auch Veranderungen im, jeweilig anderen induzieren.

The article elucidates consideration of scientific criteria for the development and design of evidence-based patient information (EBPI). Immunotherapy of multiple sclerosis serves as an example. Since in EBPI lack of evidence or ambiguities in available evidence are explicitly communicated, processing of EBPI does not necessarily lead to certainty about benefit and harms of medical interventions. However, only if the information is comprehensive in this respect can the EBPI be regarded as a robust basis for an informed choice. EBPI requires substantial developmental efforts. Regarding the growing number of medical interventions and the half-life of information, the question of responsibility for provision of EBPI is crucial. A vision is drafted in which EBPI is driven by demand of the patients and the public and is provided according to a costs-by-cause principle by those who distribute usual information hitherto. Trained patient advocates can appraise quality of information by use of instruments that consider criteria of EBPI. Critical health literacy should evolve early in school and can later on enhance usefulness of EBPI for people concerned with health issues.

Epidemiologic studies increasingly have demonstrated a correlation between physical inactivity and certain chronic diseases. Already in the 1970s exercise programs for cardiovascular patients were established, whereas in other severe chronic illnesses such as breast cancer or multiple sclerosis exposure to physical stress seemed to be a contraindication. Today there is a grow ing body of evidence demonstrating positive physical as well as psychic effects of exercise training in patients with these diseases. These studies are summarized and complementary studies of our group are described in more detail. In patients with breast cancer we were able to demonstrate persistent psychosocial effects even 1 year after completion of the training program. In patients with multiple sclerosis we could confirm an induction of neurotrophic factors in trained individuals. Correspondingly, there is accumulating evidence showing positive effects of exercise on cognitive function, especially in the aged. Potential pathophysiological pathways regarding a progression to dementia are presented. Consequently exercise programs could play a pivotal role in the prevention and therapy of the cognitive decline in the aged in an aging society.

Involving patients in medical decisions is increasingly being advocated in medical fields other than psychiatry and neurology. A model of shared decision making might prove to be an ideal way of bridging the gap between patient-centred and evidence-based medicine. This report provides a survey of this shared decision making model and a discussion of its implications in the fields of mental health and neurology.

The German Ministry for Health and Social Security is funding ten projects to introduce shared decision making into clinical practice. The medical problems the projects are focussing on were chosen from among various diseases (e. g. depression, multiple sclerosis, cancer). The ten projects achieved consensus on a core set of instruments for the measurement of process and outcome of the shared decision making. Instruments developed in German-speaking countries are currently not available. Thus, linguistic and cultural validation had to be performed for the core set instruments. The results of the data analysis as well as patient interviews demonstrate the need for improving these instruments. Therefore, the members of the methodological working group concentrated on the integration of these results in a new instrument. In a first step the construct of "shared decision making" was defined, followed by a definition of the process elements characterising shared decision making. Thereafter, items were developed on the basis of the process elements. The new instrument will now be validated for different diseases.

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.

The need for an early disclosure of the diagnosis of multiple sclerosis (MS) has become more pressing with the publication of two recent randomized trials which have indicated that very early treatment may favourably alter the disease course. We assessed the current status of diagnostic and therapeutic information on MS from the point of view of patients and neurologists.A standardized questionnaire was sent out through the patients' self-help organization in Hamburg, Germany and to all neurologists.A total of 434 of 1300 patients and 80 of 250 neurologists replied. Neurologists gave 90% of the diagnoses but only 50% of patients reported them as the major aid helping to understand the disease. Fifty per cent of patients were not informed about any form of therapy at the time of diagnosis regardless of whether their MS diagnosis was disclosed within the last 5 years or earlier. In contrast to physicians, patients voted for information about a possible MS even if the diagnosis may not yet be clear.From the patients' perspective, information about the diagnosis of MS should be more straightforward, and more information about therapies should be provided.

We describe a young man with prognostic unfavourable homoplasmatic mitochondrial DNA(mt DNA) 11778 Leber's hereditary optic neuropathy (LHON) point mutation and confirmed multiple sclerosis (MS). This combination of LHON and MS-like disease is rare in both sexes, and in men has been described in only a few case reports. In a 4-year follow-up during immunosuppressive therapy with mitoxantrone, we found a remarkable time delayed visual recovery 12 months after acute onset of rapid sequential bilateral subtotal visual loss followed by episodes of isolated acute demyelinative optic neuropathy. Visual recovery to such extent after this latency is uncommon in both mtDNA 11778 LHON mutation and optic neuritis (ON) in MS. Relapses in visual deterioration must be considered as extremely rare in LHON. This case might support the hypothesis of an immunological pathogenetic factor in combined LHON and MS, and possibly in LHON alone. We suggest a search for the LHON mutation in MS patients with predominant visual impairment, independent of patients' gender.

Cerebellar tremor is a frequent and disabling symptom in multiple sclerosis (MS) patients. Supportive pharmacological treatment with different drugs showed only minor effects in a few studies and in clinical practice. Encouraged by previous studies with ondansetron, a 5HT3-antagonist, we conducted a small open-label, prospective and controlled study with 14 MS patients suffering predominantly from cerebellar tremor of the upper extremities. Principal outcome measure to evaluate a functional improvement of the single intravenous administered ondansetron injection was the subject performance in the 9-hole-peg-test (9HPT) and 3 blind assessed upper extremity writing and copying tasks. We neither found significant improvement in the upper extremity tests nor in the subjective response of the patients. In conclusion we could not confirm a beneficial effect of ondansetron on cerebellar tremor of MS patients.

To investigate possible associations of soluble CD95 (sCD95) serum levels and DNA defragmentation with different MS disease stages and activities.Sera of 114 patients were analysed by an ELISA technique for sCD95. In a subgroup of 18 relapsing-remitting MS patients and controls we studied DNA fragmentation by the TUNEL-method in CSF cytospins.sCD95 was detectable in sera of MS patients, healthy controls and meningitis patients without significant differences. CSF specimens showed modest amounts of apoptotic cells in MS and controls.We could not demonstrate an association of MS disease course or activity with the expression of sCD95 in sera. DNA fragmentation in the CSF was not significantly enhanced compared to controls. Thus the analysed markers of programmed cell death appear not suitable to monitor MS disease courses.

Interleukin-1 (IL-1) is one of the major proinflammatory cytokines expressed consistently in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1ra) is the only known naturally occurring specific antagonistic cytokine counteracting IL-1. Thus IL-1ra may have a downregulating potential in the disease course of MS. We analysed if circulating IL-1ra could be associated with different disease stages of MS in sera of 84 MS patients and 18 controls. IL-1ra showed considerable variations in MS patients and controls. Nevertheless we found significantly elevated serum levels in active as well as in stable disease stages compared to controls. IL-1ra levels were higher in progressive disease courses compared to relapsing-remitting MS, but not statistically significant (median: 516 versus 434 pg/ml). Further analysis with larger groups of patients and longitudinal studies will clarify if IL-1ra is useful as a prognostic serum marker in MS.

In multiple planning various plans made by various planners have to be coordinated. An example is patient admission planning in hospitals. Various coordination mechanisms can be discerned that integrate multiple plans, such as rules, meta-plans and mutual adjustment. We discuss these coordination mechanisms which require external communication lines and forms, embodied in various kinds of signs. It is known that software support of single planning already requires insight in problem solving processes of planners. In multiple planning this prerequisite is even stronger. Negotiation and intelligent information interpretation are not computer oriented tasks, yet. We argue that the conceptual framework of (cognitive) semiotics is valuable in the analysis and support of multiple planning situations.

Nurse scheduling is an important, but also a very complicated management task. Performing this task results in a nursing schedule. These nursing schedules strongly influence the performance of a nursing ward. This paper describes research results on the application of several knowledge acquisition techniques for the development of a decision support system. This system informs the nurse scheduler about the quality of an arranged schedule. This paper next shows how this system can be used to improve multiple schedules in combination with the application of telematics. This improvement is based on the communication between schedulers who have a shortage or a surplus of nurses at certain days of the schedule. By means of internal reallocation of nurses for a short period of time, the total schedule quality of all nursing schedules can be improved.

We report on a typical case of intravascular lymphomatosis, a rarely diagnosed, generalised intravascular lymphoma usually of the B-cell type. In most cases there is a lack of clear haematological findings but in more than 50% intravascular lymphomatosis presents with symptoms of the central nervous system. Every rapidly progressive neurological deficit, especially the association of a subacute dementia with a spinal syndrome may suggest IVL-NS. However, careful examination may detect minor features for a systemic process in 25-80% i.e. B-symptoms elevation of ESR and LDH. Neurological imaging demonstrates multifocal lesions in the CNS with affinity to the deep white matter consistent with a microvascular or demyelinating disease. Angiographically IVL-NS may mimic cerebral vasculitis. CSF findings are nonspecific. Because diagnosis can only be made histologically, a cerebral biopsy should be undertaken in suspected cases. Usually the course of the disease is fatal. Therapy involving steroids, combination polychemotherapy or radiation met with only minor success.

An increasing number of papers deal with immunological factors in headache syndromes such as migraine and cluster headache. The aim of this review is to give an overview of the factors that have been measured and to assess their reliability and relevance for the pathogenesis of these headaches. Most of the studies are handicapped by methodological problems, especially the different classifications of headaches, the lack of adequate controls and methodological problems with the measurement of certain immune parameters. Nevertheless, immunological abnormalities have been shown to be reproducible. These are the increased number of autoantibodies in migraine and the augmented number of deficient NK cells and monocytes in cluster headache. Furthermore, some cytokine levels (IL-2) have been shown to be decreased in migraine and tension-type headache, while others (IL-1, TNFalpha) seem to be elevated. Cluster headache seems to be associated with persisting viral infections. Studies of immunoglobulins and immuncomplex levels and analyses of immunomediators such as prostaglandins and histamine still yield contradictory results. Although the immunological changes have been shown to be valid, their pathogenesis in these headaches is unclear. With the increasing recognition of the existence of a neuroimmunologic network, alterations in each system should always be considered to be associated with changes in an other. Acute or chronic pain seems to trigger immunological abnormalities.

Uncontaminated intertidal mussels transferred to a tautline buoy system near a major submarine outfall off southern California proved to be useful bio-indicators of water column contamination. Mussel survival exceeded 90%, and specimens maintained for 13 weeks near the polluted bottom (35 m) and the sea surface accumulated DDT above control concentrations by factors of 200 and 20, respectively. Corresponding factors for PCB were 60 and 6.

A rapid technique for the determination of dry aerial fall-out fluxes of higher molecular weight chlorinated hydrocarbons by collecting particles on a mineral-oil-coated glass plate has been successfully adapted for collection of certain DDT and PCB residues over a 1-week period. However, the technique proved unsatisfactory for components more volatile than p , p ′-DDE. Comparison of fall-out fluxes measured by this collector with these measured by one that freezes fall-out particles in a layer of ice provided relatively good agreement between mean values for total DDT and PCB 1254.

Despite major decreases in DDT and PCB emissions over a three year period by the dominant discharger to a coastal marine site, only minor (and very similar) decreases were observed in concentrations of these pollutants in bottom sediments and flatfish from the outfall monitoring zone. These results illustrate how persistant such chlorinated hydrocarbons can be in the marine environment once the bottom sediments have been contaminated.

The waters near the Los Angeles County ocean outfalls at Whites Point, California were examined for chlorinated hydrocarbon contaminants. Transplanted mussels were suspended at the monitoring site for 2 months to provide a measure of those chlorinated hydrocarbons which bioaccumulate; and a moored water sampling instrument was deployed at the same site to measure chlorinated hydrocarbons in the water column by in situ concentration on extraction columns. The in situ water sampler permitted detection limits of approximately 0.05 ng l−1 for individual compounds. The DDT family (primarily the metabolites DDD and DDE) were found at concentrations up to 2 ng l−1. None of the cyclodiene family of pesticides (heptachlor, heptachlor epoxide, aldrin, dieldrin, endrin), nor any of the PCB family (measured as Aroclor 1242 and Aroclor 1254) were detected. The transplanted mussels gave results similar to the in situ water sampler for DDT and cyclodiene families: DDD and DDE, but very little DDT were bioaccumulated to give total DDT concentrations of 360±60 μg−1 kg wet weight. None of the cyclodiene family of pesticides were detected. However, the PCB family were concentrated, from below the detection limit in the in situ water sampler, to levels in mussel tissue of 97±13 μg kg−1 wet weight. The bioaccumulation factor (mussel:water concentrations) for total DDT was approximately 100 000, similar to values reported previously. The concentration of total DDT in the effluent is extremely low, averaging less than 0.1 μg l−1. Dilution considerations suggest that the source of the DDT in the water column is primarily the sediments (historical emissions) rather than the present effluent.