Peripapillary retinal nerve fibre layer thinning rate as a biomarker discriminating stable and progressing relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Peripapillary retinal nerve fibre layer (pRNFL) thickness is a strong candidate as a biomarker of axonal degeneration in multiple sclerosis (MS). The aim was to determine a cut-off value of pRNFL thinning rates in relapsing-remitting MS (RRMS) to discriminate between stable and progressing patients. METHODS: In this 3-year prospective longitudinal study on 141 RRMS patients, annual pRNFL thinning rates (aLpRNFL) were determined by individual linear regression models. The best possible cut-off value discriminating clinically progressing (physical progression or cognitive decline) and stable patients was defined by receiver operating characteristic analysis. Cut-off values were validated using a multivariate logistic regression model. RESULTS: Average aLpRNFL in progressing patients (2.4 µm, SD 2.1) was significantly higher compared to stable patients (0.5 µm, SD 1.2, P < 0.001). At a predefined specificity of 90%, aLpRNFL >1.5 µm was able to distinguish between stable and progressing RRMS with a sensitivity of 76.1%. aLpRNFL >1.5 µm was associated with a 15-fold increased risk of clinically progressing MS (P < 0.001). CONCLUSIONS: A cut-off of aLpRNFL discriminating clinically progressing and stable RRMS was identified. After validation in independent cohorts, this cut-off could be used as a biomarker of axonal degeneration supporting disease monitoring in daily clinical routine.

Combined evaluation of personality, risk and coping in MS patients: A step towards individualized treatment choice - The PeRiCoMS-Study I.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory neurological disease requiring disease-modifying treatment (DMT). To provide patients with the optimal individual therapeutic option, treatment recommendations should be based not only on individual disease course and DMT specific benefit-risk estimates, but also on patient's individual characteristics such as personality, risk attitude and coping strategies. However, these characteristics are difficult to objectify in clinical routine practice without the support of appropriate evaluation instruments. OBJECTIVE: To identify and to assemble an objective test battery measuring personality, risk attitude and coping strategies in MS patients. METHODS: A comprehensive literature search was performed to obtain all questionnaires assessing personality, risk attitude and coping strategies. Availability in German language, validation in a published normative collective and a reliability of >0.70 were required for our purposes. Based on these criteria, we chose the Big-Five-Personality Test, UPPS Impulsive Behaviour Scale, Domain-Specific Risk-Taking scale (DOSPERT), Brief-COPE and Stress & Coping Inventory (SCI). Results were compared to published normative controls of the respective questionnaires. RESULTS: Out of 22 MS patients (7 males, 15 females) participating in this study, 19 (86.4%) completed all questionnaires. The median completion time was 45min (min-max range: 25-60min). The median scores of the MS group were within the average range of published control samples in all questionnaires. CONCLUSIONS: We report that traits of personality, risk attitude and coping strategies can be effectively and feasibly tested in MS patients by the instruments used in our exploratory study. There were no differences between MS patients and healthy controls, thus enabling assessment without being influenced by the diagnosis of MS. After validation in a larger cohort the "PeRiCoMS"-battery will be useful as another step towards a more individualized shared-decision-making in every day routine practice.

Monoclonal antibodies in the treatment of multiple sclerosis.

Multiple sclerosis (MS), a chronic demyelinating disorder, is characterized by recurrent neurological deficits or progressive impairment with a high risk of permanent disability. Since the exact pathophysiology and etiology remains still unclear, no curing therapy is currently available. However, several treatments with beneficial effect on relapse rate such as the first line therapies interferon-beta and glatiramer acetate were approved for relapsing-remitting MS. One new important tool in the therapy of MS is the use of monoclonal antibodies. Natalizumab is the first and so far only monoclonal antibody that is approved for MS treatment by the US Food and Drug Administration and the European Medicines Agency. In addition to natalizumab other monoclonal antibodies previously used in cancer and other autoimmune disorders or even newly developed for MS are now being tested in clinical trials. With their high target specificity and efficacy monoclonal antibodies are a promising treatment approach in MS. This review summarizes the present knowledge on the use, effectiveness and safety of monoclonal antibodies in MS treatment.

Smoking is a risk factor for early conversion to clinically definite multiple sclerosis.

BACKGROUND: Cigarette smoking increases the risk for development of multiple sclerosis and modifies the clinical course of the disease. In this study, we determined whether smoking is a risk factor for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome. METHODS: We included 129 patients with a clinically isolated syndrome, disseminated white-matter lesions on brain magnetic resonance imaging, and positive oligoclonal bands in the cerebrospinal fluid. The patients' smoking status was obtained at the time of the clinically isolated syndrome. RESULTS: During a follow-up time of 36 months, 75% of smokers but only 51% of non-smokers developed clinically definite multiple sclerosis, and smokers had a significantly shorter time interval to their first relapse. The hazard ratio for progression to clinically definite multiple sclerosis was 1.8 (95% confidence interval, 1.2-2.8) for smokers compared with non-smokers (P = 0.008). CONCLUSIONS: Smoking is associated with an increased risk for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome, and our results suggest that smoking is an independent but modifiable risk factor for disease progression of multiple sclerosis. Therefore, it should be considered in the counseling of patients with a clinically isolated syndrome.