Mental health problems in children of somatically ill parents, e.g. multiple sclerosis

Objectives: Based on the investigation of 144 families (144 patients affected by Multiple Sclerosis (MS), 109 partners, and 192 children) examined in three different European child and adolescent psychiatric University centres by means of questionnaires, we evaluated the prevalence of psychological symptoms in the offspring and associated risk factors such as duration and severity of the disease as well as depression of the ill and the healthy parent. Results: Indicate that the severe disease of MS is associated with depression of the ill and healthy parent. Ill parents, especially ill mothers, as well as depressed ill, or depressed healthy parents evaluate their children's mental health problems with a higher prevalence within the internalizing spectrum. Healthy parents report normal psychological adjustment of their children. If two parents present a depressive state, the prevalence of relevant psychological internalizing symptoms is twice or three times as high as the age norms. Conclusion: Children in families with a parent affected by MS and associated depression of the parental couple are at high risk of mental health problems, especially internalizing disorders. In focusing on the mental health of children one must also be aware of the potential opportunities to address the parents' own psychological need

Changes in the Cerebrospinal Fluid and Plasma Lipidome in Patients with Rett Syndrome

Rett syndrome (RTT) is defined as a rare disease caused by mutations of the methyl-CpG binding protein 2 (MECP2). It is one of the most common causes of genetic mental retardation in girls, characterized by normal early psychomotor development, followed by severe neurologic regression. Hitherto, RTT lacks a specific biomarker, but altered lipid homeostasis has been found in RTT model mice as well as in RTT patients. We performed LC-MS/MS lipidomics analysis to investigate the cerebrospinal fluid (CSF) and plasma composition of patients with RTT for biochemical variations compared to healthy controls. In all seven RTT patients, we found decreased CSF cholesterol levels compared to age-matched controls (n = 13), whereas plasma cholesterol levels were within the normal range in all 13 RTT patients compared to 18 controls. Levels of phospholipid (PL) and sphingomyelin (SM) species were decreased in CSF of RTT patients, whereas the lipidomics profile of plasma samples was unaltered in RTT patients compared to healthy controls. This study shows that the CSF lipidomics profile is altered in RTT, which is the basis for future (functional) studies to validate selected lipid species as CSF biomarkers for RTT

Atorvastatin added to interferon beta for relapsing multiple sclerosis: a randomized controlled trial

Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3months, they were randomized 1:1 to receive atorvastatin 40mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95% CI 0.36-3.56; p=0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p=0.02). In conclusion, atorvastatin 40mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month perio

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Mental health problems in children of somatically ill parents, e.g. multiple sclerosis

Objectives Based on the investigation of 144 families (144 patients affected by Multiple Sclerosis (MS), 109 partners, and 192 children) examined in three different European child and adolescent psychiatric University centres by means of questionnaires, we evaluated the prevalence of psychological symptoms in the offspring and associated risk factors such as duration and severity of the disease as well as depression of the ill and the healthy parent. Results Indicate that the severe disease of MS is associated with depression of the ill and healthy parent. Ill parents, especially ill mothers, as well as depressed ill, or depressed healthy parents evaluate their children’s mental health problems with a higher prevalence within the internalizing spectrum. Healthy parents report normal psychological adjustment of their children. If two parents present a depressive state, the prevalence of relevant psychological internalizing symptoms is twice or three times as high as the age norms. Conclusion Children in families with a parent affected by MS and associated depression of the parental couple are at high risk of mental health problems, especially internalizing disorders. In focusing on the mental health of children one must also be aware of the potential opportunities to address the parents’ own psychological needs

Changes in the Cerebrospinal Fluid and Plasma Lipidome in Patients with Rett Syndrome

Rett syndrome (RTT) is defined as a rare disease caused by mutations of the methyl-CpG binding protein 2 (MECP2). It is one of the most common causes of genetic mental retardation in girls, characterized by normal early psychomotor development, followed by severe neurologic regression. Hitherto, RTT lacks a specific biomarker, but altered lipid homeostasis has been found in RTT model mice as well as in RTT patients. We performed LC-MS/MS lipidomics analysis to investigate the cerebrospinal fluid (CSF) and plasma composition of patients with RTT for biochemical variations compared to healthy controls. In all seven RTT patients, we found decreased CSF cholesterol levels compared to age-matched controls (n = 13), whereas plasma cholesterol levels were within the normal range in all 13 RTT patients compared to 18 controls. Levels of phospholipid (PL) and sphingomyelin (SM) species were decreased in CSF of RTT patients, whereas the lipidomics profile of plasma samples was unaltered in RTT patients compared to healthy controls. This study shows that the CSF lipidomics profile is altered in RTT, which is the basis for future (functional) studies to validate selected lipid species as CSF biomarkers for RTT

Association of Rituximab Treatment with Disability Progression among Patients with Secondary Progressive Multiple Sclerosis

Importance: Therapeutic options for patients with secondary progressive multiple sclerosis (SPMS) are limited. Objective: To analyze disability progression in patients with SPMS treated with rituximab compared with matched control patients never treated with rituximab. Design, Setting, and Participants: This retrospective cohort study analyzed data obtained from patients with SPMS at 3 multiple sclerosis centers located in Basel and Lugano, Switzerland, and Amsterdam, the Netherlands, from 2004 to 2017. Patients were included for analysis if they had received a diagnosis of SPMS, were treated (57 eligible; 54 included) or never treated (504 eligible; 59 included) with rituximab, and had at least 1 follow-up visit. The variables used for propensity score matching were sex, age, Expanded Disability Status Scale (EDSS) score, and disease duration. Follow-up duration was up to 10 years, with a mean (SD) of 3.5 (2.6) years for rituximab-treated patients and 5.4 (2.4) years for controls in the total cohort and a mean (SD) of 3.5 (2.7) years for rituximab-treated patients and 4.8 (2.2) years for controls in the matched cohort. Exposures: Comparing EDSS score progression in patients with SPMS (treated with rituximab vs not treated with rituximab) using propensity score matching. Main Outcomes and Measures: The primary end point was progression of EDSS score after baseline, and the secondary end point was time to confirmed disability progression. Results: After 1:1 propensity score matching, 44 matched pairs (88 patients) were included in the analysis. At baseline, patients treated with rituximab had a mean (SD) age of 49.7 (10.0) years, mean (SD) disease duration of 18.2 (9.4) years, and mean (SD) EDSS score of 5.9 (1.4), and 26 (59%) were women, whereas controls had a mean (SD) age of 51.3 (7.4) years, mean (SD) disease duration of 19.4 (8.7) years, and mean (SD) EDSS score of 5.70 (1.29), and 27 (61%) were women. In the covariate-adjusted analysis of the matched set, patients with SPMS who were treated with rituximab had a significantly lower EDSS score during a mean (SD) follow-up of 3.5 (2.7) years (mean difference, -0.52; 95% CI, -0.79 to -0.26; P <.001). Time to confirmed disability progression was significantly delayed in the rituximab-treated group (hazard ratio, 0.49; 95% CI, 0.26-0.93; P =.03). Conclusions and Relevance: In this study, patients with SPMS treated with rituximab had a significantly lower EDSS score for up to 10 years of follow-up and a significantly delayed confirmed progression compared with matched controls, suggesting that B-cell depletion by rituximab may be therapeutically beneficial in these patients. A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients

Sit-to-stand biomechanics : a systematic review

Objective: This review focuses on studies that enhance our knowledge of the biomechanics of the sit-to-stand (STS) quantitatively. The questions asked and the methods of study have led to the partitioning of the STS into components, or phases. Our goal is to summarize the methodological approaches and define the phases of a STS transfer in order to provide a standard practice for STS. Data Sources: Electronic database searches were conducted in PubMed and Google Scholar from inception to February 2021. Study Selection: Articles with a combination of the keywords “sit-to-stand”, “biomechanics”, “stability” and “postural control” were searched. Only the articles that provided quantitative biomechanical insights of the STS movement were included. Data Extraction: We categorized the studies by the questions posed, the measurement techniques used, and the definition of phases. Data Synthesis: Seventy-two papers published between 1976 and 2021 that provided quantitative biomechanical insights of the STS movement itself were included in this review. Among the studies that qualified for this review, research interest in the STS may be parsed into the following categories: a) how the movement is performed, b) use of the STS to understand postural stability, and c) use of the STS to understand clinical differences in performance. Conclusion: Definitions of events in the STS that define phases are inconsistent. The major reason identified is due to differences in the purpose of the studies or equipment used. Four studies dividing STS into 2 phases, eight studies divided STS into 3 phases, and 2 studies divided STS into 4 phases and 2 studies divided STS into 5 phases. At a minimum, the STS is typically deconstructed into two phases, with seat-off being the demarcation of transition between phases. This is based on the characteristics of muscle power or on select kinematic events. However, 10 different ways in which the event of ‘seat-off’ has been defined shows the impact of differences in measurement technique. These differences between studies result in contradictory definitions of the same event. These findings reveal a need for standardization of event definition and recommendations on measurement techniques.Kinesiology and Health Educatio