[Nutrition, microbiome and multiple sclerosis : Current knowledge from basic research and clinical practice]. / Ernährung, Mikrobiom und Multiple Sklerose : Aktuelle Erkenntnisse aus der Grundlagenforschung und der Klinik.

Epidemiological data indicate a disproportional increase in the incidence of multiple sclerosis (MS) over the last decades, particularly in industrialized countries. Although this increase is also associated with altered diagnostic criteria and improved sensitivity of imaging procedures, current data suggest that particularly alterations in our way of life play an important role. In recent years the importance of the gut and intestinal microbiome for some neurological diseases and in particular for MS was recognized. Because nutritional habits have a substantial influence on the composition of the microbiome and our nutrition has changed considerably in the last decades, nutritional components can play an important role in the pathogenesis of MS. In this further education article we summarize the currently available evidence on the role of the gut and on the effects of dietary components on the microbiome in the pathogenesis of MS.

[Monitoring of blood parameters under course-modified MS therapy : Substance-specific relevance and current recommendations for action]. / Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie : Substanzspezifische Relevanz und aktuelle Handlungsempfehlungen.

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.

[Current aspects of therapy conversion for multiple sclerosis]. / Aktuelles zur Therapieumstellung bei Multipler Sklerose.

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.

[Fumaric acid as therapeutic agent for multiple sclerosis]. / Fumarsäure in der Therapie der Multiplen Sklerose.

After the approval of fumaric acid in February 2014 another first line agent is now available for the treatment of multiple sclerosis (MS). Along with the various beta interferon preparations, glatiramer acetate, teriflunomide and fumaric acid add to the repertoire of oral therapeutics for the initial treatment of relapsing remitting MS in daily practice. In order to employ these drugs in an individualized and precise medical manner and considering their efficacy and side effects, it seems worthwhile to learn the so far known mode of action and background history. Fumaric acid, as one of the newest drugs approved for MS, reveals the longest history as it was in use for decades as a treatment in psoriasis patients. Furthermore, fumaric acid is a good example for so far not extensively exploited option of drug reposition in medicine in general. The current review summarizes the outcomes of the clinical approval studies of fumaric acid in MS and discusses the dual mode of action, the immunomodulatory and tissue protective effect, as well as the reported adverse events under fumaric acid treatment. This review aims to serve an aid in the daily decision-making practice when choosing the baseline therapy for MS patients.

Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease developing towards the end of pregnancy or in the months following delivery in previously healthy women in terms of cardiac disease. Enhanced oxidative stress and the subsequent cleavage of the nursing hormone Prolactin into an anti-angiogenic 16 kDa subfragment emerged as a potential causal factor of the disease. We established a prospective registry with confirmed PPCM present in 115 patients (mean baseline left ventricular ejection fraction, LVEF: 27 ± 9 %). Follow-up data (6 ± 3 months) showed LVEF improvement in 85 % and full recovery in 47 % while 15 % failed to recover with death in 2 % of patients. A positive family history of cardiomyopathy was present in 16.5 %. Pregnancy-associated hypertension was associated with a better outcome while a baseline LVEF ≤ 25 % was associated with a worse outcome. A high recovery rate (96 %) was observed in patients obtaining combination therapy with beta-blocker, angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor-blockers (ARBs) and bromocriptine. Increased serum levels of Cathepsin D, the enzyme that generates 16 kDa Prolactin, miR-146a, a direct target of 16 kDa Prolactin, N-terminal-pro-brain-natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) emerged as biomarkers for PPCM. In conclusion, low baseline LVEF is a predictor for poor outcome while pregnancy-induced hypertensive disorders are associated with a better outcome in this European PPCM cohort. The high recovery rate in this collective is associated with a treatment concept using beta-blockers, ACE inhibitors/ARBs and bromocriptine. Increased levels of Cathepsin D activity, miR-146a and ADMA in serum of PPCM patients support the pathophysiological role of 16 kDa Prolactin for PPCM and may be used as a specific diagnostic marker profile.

Medical graphics to improve patient understanding and anxiety in elderly and cognitively impaired patients scheduled for transcatheter aortic valve implantation (TAVI).

BACKGROUND: Anxiety and limited patient comprehension may pose significant barriers when informing elderly patients about complex procedures such as transcatheter aortic valve implantation (TAVI). OBJECTIVES: We aimed to evaluate the utility of medical graphics to improve the patient informed consent (IC) before TAVI. METHODS: In this prospective, randomized dual center study, 301 patients were assigned to a patient brochure containing medical graphics (Comic group, n = 153) or sham information (Control group, n = 148) on top of usual IC. Primary outcomes were patient understanding of central IC-related aspects and periprocedural anxiety assessed by the validated Spielberger State Trait Anxiety Inventory (STAI), both analyzed by cognitive status according to the Montreal Cognitive Assessment (MoCA). RESULTS: Patient understanding was significantly higher in the Comic group [mean number of correct answers 12.8 (SD 1.2) vs. 11.3 (1.8); mean difference 1.5 (95% CI 1.2-1.8); p < 0.001]. This effect was more pronounced in the presence of cognitive dysfunction (MoCA < 26) [12.6 (1.2) in the Comic vs. 10.9 (1.6) in the Control group; mean difference 1.8 (1.4-2.2), p < 0.001]. Mean STAI score declined by 5.7 (95% CI 5.1-6.3; p < 0.001) in the Comic and 0.8 points (0.2-1.4; p = 0.015) in the Control group. Finally, mean STAI score decreased in the Comic group by 4.7 (3.8-5.6) in cognitively impaired patients and by 6.6 (95% CI 5.8 to 7.5) in patients with normal cognitive function (p < 0.001 each). CONCLUSIONS: Our results prove beneficial effects for using medical graphics to inform elderly patients about TAVI by improving patient understanding and reducing periprocedural anxiety (DRKS00021661; 23/Oct/2020). Medical graphics entailed significant beneficial effects on the primary endpoints, patient understanding and periprocedural anxiety, compared to the usual patient informed consent (IC) procedure. Patient understanding of IC-related aspects was significantly higher in the Comic group, with a more pronounced benefit in patients with cognitive impairment (p for IC method and cognitive status < 0.001, respectively; p for IC method x MoCA category interaction = 0.017). There further was a significant decline of periprocedural anxiety in patients with and without cognitive impairment (p for IC method x measuring time point < 0.001; p for IC method x MoCA category x measuring time point interaction = 0.018).

Reproductive counselling, treatment and course of pregnancy in 73 German MS patients.

Multiple sclerosis (MS) often affects women during the reproductive years of their life. During this period, issues such as choice of immunomodulatory treatment, seeking advice from specialists, relapse-induced steroid application before, during or after pregnancy in combination with breastfeeding gain importance. The objective was to investigate these issues retrospectively using a questionnaire among 73 MS patients with a total of 88 pregnancies. Eighty per cent of the participants consulted their neurologists before and 60% during pregnancy. The annual relapse rate decreased during pregnancy and significantly increased during the first 3 months after delivery. Immunomodulatory treatment was stopped due to desired pregnancy for a mean of 4 years. Fourteen of the MS patients received intravenous immunoglobulin treatment post-natal. Ninety per cent of the study subjects started breastfeeding. However, nearly 30% ablactated, as they received steroids due to a relapse. Weight and height of the full-term children of singleton pregnancies from MS patients were significantly lower compared with the ones of age-matched healthy controls. Our results confirm the known reduced relapse rate during pregnancy, which is followed by an increased relapse rate after delivery. They shed light on the epidemiology of childbirth in patients with MS.

Cervical cord area is associated with infratentorial grey and white matter volume predominantly in relapsing-remitting multiple sclerosis: A study using semi-automated cord volumetry and voxel-based morphometry.

BACKGROUND AND PURPOSE: Atrophy of the brain and the upper cervical cord, which both have major impact on the severity of clinical symptoms in multiple sclerosis (MS), may be interrelated by neuraxonal degeneration. Aiming to identify possible spatially remote effects of neuraxonal brain damage on spinal cord atrophy, we studied regional and global brain volumes and the upper cervical cord area (UCCA) in a large group of MS patients and a healthy control group. METHODS: In a group of 132 MS patients (71 relapsing-remitting MS; 61 secondary progressive MS; median [range] of EDSS: 5 [0-7], respectively 6 [2-8.5] and mean±standard deviation of age/disease duration: 37±11 years/6.7±6.3 years; respectively: 49±8 years/14.5±8.0 years) and 45 healthy subjects UCCA, regional and global brain volumes, and brain lesion load were assessed. Associations between MRI results and clinical parameters in the entire cohort and differentiated according to MS-subtype were investigated using t-tests, partial correlation analyses, voxel-based morphometry and statistical parametric mapping. RESULTS: Exclusively in RRMS, a significant positive correlation of UCCA with cerebellar cortical grey matter (GM) in the vermis and with regional white matter volume in the entire brainstem, corresponding to the corticospinal tracts, was detected. Although SPMS patients were considerably more affected by disability and decrease of UCCA (RRMS:75.2±10.4 mm(2); SPMS: 66.0±11.8 mm(2),controls: 84.5±8.7mm(2)), brain grey matter (RRMS:585.8±53.6 ml; SPMS: 528.2±61.5 ml, controls: 608.7±48.1 ml) and total brain volume (RRMS:1162.9±41.8 ml; SPMS: 1117.9±51.2 ml, controls: 1194.1±19.5 ml) than RRMS patients, significant positive associations in this group were found only between UCCA and a cluster of white matter in the medulla, but not in grey matter. CONCLUSION: Cervical cord and brain atrophy were present in both, RRMS and even more severe in SPMS. Still, spatial associations between cervical cord area and remote cerebellar and brainstem volume, possibly driven by neuraxonal degeneration, were detected mostly in RRMS patients with predominantly short disease durations. Future longitudinal studies may elucidate the interplay between affection of spinal cord and infratentorial structures in MS, and contribute to the understanding of the conversion processes from relapsing-remitting to secondary progressive MS.

Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort.

OBJECTIVE: To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010. RESULTS: Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML. CONCLUSIONS: These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.

[Open use of natalizumab. Neutralising antibodies and clinical data]. / Natalizumab im klinischen Alltag. Neutralisierende Antikörper und klinische Daten.

BACKGROUND: Since June 2006 natalizumab has been available for use as monotherapy in relapsing-remitting MS with high disease activity. The AFFIRM study showed the occurrence of persisting and neutralising antinatalizumab antibodies (nAb) in 6% of the patients. We present data revealing the number of nAb-positive patients assessed in our independent laboratory. Additionally we provide retrospective clinical data on the efficacy of natalizumab as escalating immunotherapy. PATIENTS AND METHODS: Blood samples of patients treated with natalizumab in Germany were tested for nAb using an enzyme-linked immunosorbent assay. If nAb were detectable at a single time point, the according patients were categorised as transiently positive. They were diagnosed as persistently positive if they had nAb at two or more time points which were at least 6 weeks apart. The treating neurologists sending the serum samples were asked to provide clinical data of their patients. RESULTS: Forty-seven of 593 samples (9.1%) were nAb-positive, 19 of them (3.7%) persistently positive and two (0.3%) transiently. Twenty-six patients (5%) were not retested for nAb, as we did not receive material for confirmatory analysis. Infusion-related adverse events were reported for 53 patients (10.3%). Averages of 2.6 relapses per year were reported previous to natalizumab therapy and 0.3 per year during natalizumab therapy. CONCLUSION: During natalizumab therapy, testing for nAb should be strongly considered for further therapy decisions and in cases of suspected allergic reaction. Basically the obtained data compare with those of the AFFIRM study. Natalizumab is applied as escalating therapy in MS according to the recommendations of the MSTKG, and it seems to match the expectations in open-label use.