Eye movement desensitization and reprocessing for depressed individuals with multiple sclerosis: A pilot study.

BACKGROUND: Multiple studies have highlighted elevated rates of depression among individuals with Multiple Sclerosis (MS), with its associated symptoms posing a significant threat to overall well-being. Moreover, existing literature suggests a potential interconnection between depressive manifestations and the decline of physical functionalities in the context of MS. OBJECTIVE: to examine the viability of the Eye Movement Desensitization Reprocessing (EMDR) therapy protocol for the treatment of depressive disorders (DeprEND) for alleviating depression in individuals with MS. METHODS: We conducted a process-outcome study to examine the feasibilty and effectiveness DeprEND enrolling 13 individuals with MS and depressive symtpoms. Psychological and physical assessment pre-, post-intervention and 3-month follow-up were included. Pre- and post-magnetic resonance imaging (MRI) scans were conducted to analyze potential alterations in brain function. RESULTS: The EMDR DeprEND treatment showed a high level of adherence and feasibility. Significant reductions in depressive symptoms were found at post-intervention and at 3 months follow-up. No significant differences were observed in terms of physical symptoms. A significant modulation observed in parietal and premotor areas when examining negative valence stimuli post-treatment was found. CONCLUSION: for The EMDR DeprEND protocol may represent a feasible and cost-effective treatment for reducing depressive symptoms in MS patients and improving their mental well-being.

Mindfulness-Based Interventions for the Improvement of Well-Being in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: The study aims to meta-analytically review studies about the effects of mindfulness-based interventions (MBIs) on well-being of people with multiple sclerosis (MS). METHODS: Seven electronic databases were searched from June 2018 to September 2018. A systematic review and a meta-analysis were conducted. RESULTS: Twenty-one studies were included in qualitative synthesis, and 10 studies were included in meta-analysis. MBIs are effective with an overall moderate effect size (Hedges' g = 0.70) in improving well-being in people with MS, with lasting effects at the follow-up (g = 0.55). In particular, MBIs demonstrated to highly reduce stress (g = 1.07) and to improve depression and anxiety symptoms with a moderate to large effect at postintervention (g = 0.77 and g = 0.63, respectively). CONCLUSIONS: MBIs represent a valid and effective mind-body intervention to improve the well-being of patients with MS. Further studies should investigate which components of MBIs could be more beneficial for patients with progressive MS. PROSPERO REGISTRATION: CRD42018099704.

Longitudinal associations between mindfulness and well-being in people with multiple sclerosis.

Background/Objective: Depression, anxiety, fatigue, and sleep problems are typical conditions reported in people with multiple sclerosis (MS), often resulting in a reduction of their quality of life (QOL) and well-being. Mindfulness is a multifaceted and complex construct that has been increasingly explored for its correlated to well-being. Despite preliminary evidence, longitudinal data about the impact of mindfulness on QOL in MS remain limited. In addition, Langerian mindfulness, one of the prominent approaches to mindfulness, is yet unexplored in this field. The study aims to examine the longitudinal relationships between two forms of mindfulness (Langerian and contemplative) and QOL, anxiety, depression, fatigue, and sleep. Method: Within a larger randomized controlled trial of an online mindfulness-based stress reduction intervention, a cohort of 156 people with MS was recruited and assessed for both mindfulness constructs, QOL, anxiety, depression, fatigue, and sleep problems. Assessments were repeated after 2 and after another 6 months. Results: Both mindfulness constructs were highly correlated with all investigated outcomes. Both Langerian and contemplative mindfulness predicted higher QOL, lower anxiety, depression, fatigue, and sleep, over time. Conclusions: In both approaches dispositional mindfulness is a protective factor against depression, anxiety, fatigue, and sleep in people with MS.

Antecedentes/Objetivo: La depresión, la ansiedad, la fatiga y los problemas para dormir son condiciones típicas en personas con esclerosis múltiple (EM), que a menudo conllevan una reducción de su calidad de vida (CV). El mindfulness es una construcción compleja y multifacética que ha sido cada vez más explorada por su correlación con el bienestar. Sin embargo, los datos longitudinales sobre el impacto del mindfulness en la calidad de vida en la EM siguen siendo limitados. Este estudio tiene como objetivo examinar las relaciones longitudinales entre dos formas de mindfulness con la calidad de vida, la ansiedad, la depresión, la fatiga y el sueño. Método: Se contó con una muestra de 156 personas con EM y se evaluaron los constructos de mindfulness, calidad de vida, ansiedad, depresión, fatiga y problemas de sueño. Las evaluaciones se repitieron después de 2 y 6 meses. Resultados: Ambos constructos de mindfulness estuvieron altamente correlacionados con todos los resultados investigados, y ambos predijeron mayor CV, menor ansiedad, depresión, fatiga y problemas de sueño con el tiempo. Conclusiones: El mindfulness es un factor de protección contra la depresión, la ansiedad, la fatiga y el sueño en personas con EM.

Online meditation training for people with multiple sclerosis: A randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) has a relevant impact on quality of life (QOL) and is associated with increased risks of psychological morbidity. Mindfulness-based interventions (MBIs) are among the most studied interventions, although few well-conducted studies have tested them in this field. Furthermore, the participation in typical MBIs may be impaired by time and logistics. OBJECTIVE: We aimed to test the efficacy of an online MBI to improve QOL, psychological well-being, sleep, and fatigue. METHODS: We conducted a randomized controlled trial, in which 139 participants were randomly assigned to an MS-specific online mindfulness meditation intervention or to a psychoeducational (active control) group. Participants were assessed for QOL, depression, anxiety, sleep problems, and fatigue, at three different times: at recruitment, after 2 months, and after 6 months. RESULTS: In comparison to the control group, the experimental subjects reported higher QOL and lower depression, anxiety, and sleep problems at the end of intervention. However, after 6 months these group differences were no longer significant. CONCLUSION: An online MBI could be an effective psychological treatment for the promotion of well-being in MS in short-term. However, the lack of lasting effects requires the development of new strategies to support long-term changes.

Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study).

BACKGROUND: The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients. METHODS: We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis. RESULTS: During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07-2.41, p<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46-0.56, p<0.001) were predictive of treatment discontinuation. CONCLUSION: These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, thus avoiding the cost of longer term evaluation.

A telemedicine meditation intervention for people with multiple sclerosis and their caregivers: study protocol for a randomized controlled trial.

BACKGROUND: Mindfulness-based interventions, modified and shortened versions of meditation teachings, have proved to be effective in the improvement of quality of life in many clinical conditions, including chronic diseases. Preliminary results available in the literature and in clinical experience indicate a high potential for this treatment for the reduction of psychological suffering in people with chronic diseases. METHODS/DESIGN: This randomized controlled trial will investigate the impact of a multiple sclerosis (MS) specific telemedicine meditation intervention on the quality of life of people with multiple sclerosis and their caregivers. This trial will recruit 120 patients, men and women, with a diagnosis of relapsing-remitting or secondary progressive MS and their caregivers to participate in a 2-month intervention. Patients will undergo assessments of quality of life, anxiety, depression, quality of sleep, mindfulness and fatigue levels conducted at baseline, at week 8 (conclusion of the intervention) and at week 27 (6 months follow-up). Caregivers will complete assessments conducted at the same time for the same areas, plus caregiver burden. The intervention condition will consist of 2 hours/week of online meditation in a group setting led by a trainer, plus 1 hour/week of individual exercises. The control condition will incorporate a psycho-education online program and will require the same contact time commitment as the intervention condition. DISCUSSION: Primary outcome measures will consist of assessments of quality of life, anxiety, and depression level. Assessments of mindfulness level, quality of sleep and fatigue level will be considered secondary outcome measures. This investigation will increase understanding of the role of meditation as part of a treatment plan for people with MS and their caregivers. Overall, this study design has the potential to lead to effective meditation intervention strategies for this population and improve their quality of life. TRIAL REGISTRATION: Clinical Trials Register NCT02364505. https://clinicaltrials.gov/ct2/show/NCT02364505.

Mitoxantrone for multiple sclerosis.

BACKGROUND: This is an updated Cochrane review of the previous published version.Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients. OBJECTIVES: The main objective was to assess the efficacy and safety of MX compared to a control group in relapsing-remitting (RRMS), progressive relapsing (PRMS) and secondary progressive (SPMS) MS participants. SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (June 2012) and reference lists of articles. We also undertook handsearching and contacted trialists and pharmaceutical companies. SELECTION CRITERIA: Randomised, double-blinded, controlled trials (RCTs) comparing the administration of MX versus placebo or MX plus steroids treatment versus placebo plus steroids treatment were included. DATA COLLECTION AND ANALYSIS: The review authors independently selected articles for inclusion. They independently extracted clinical, safety and magnetic resonance imaging (MRI) data, resolving disagreements by discussion. Risk of bias was evaluated to assess the quality of the studies. Treatment effect was measured using odds ratios (OR) with 95% confidence intervals (CI) for the binary outcomes and mean differences (MD) with 95% CI for the continuous outcomes. If heterogeneity was absent, a fixed-effect model was used. MAIN RESULTS: Three trials were selected and 221 participants were included in the analyses. MX reduced the progression of disability at two years follow-up (proportion of participants with six months confirmed progression of disability (OR 0.30, 95% CI 0.09 to 0.99 and MD -0.36, 95% CI- 0.70 to -0.02; P = 0.04)). Significant results were found regarding the reduction in annualised relapse rate (MD -0.85, 95% CI -1.47 to -0.23; P = 0.007), the proportion of patients free from relapses at one year (OR 7.13, 95% CI 2.06 to 24.61; P = 0.002) and two years (OR 2.82, 95% CI 1.54 to 5.19; P = 0.0008), and the number of patients with active MRI lesions at six months or one year only (OR 0.24, 95% CI 0.10 to 0.57; P = 0.001). Side effects reported in the trials (amenorrhoea, nausea and vomiting, alopecia and urinary tract infections) were more frequent in treated patients than in controls, while no major adverse events have been reported. These results should be considered with caution because of the heterogeneous characteristics of included trials in term of drug dosage, inclusion criteria and quality of included trials. Moreover, it was not possible to estimate the long-term efficacy and safety of MX. AUTHORS' CONCLUSIONS: MX shows a significant but partial efficacy in reducing the risk of MS progression and the frequency of relapses in patients affected by worsening RRMS, PRMS and SPMS in the short-term follow-up (two years). No major neoplastic events or symptomatic cardiotoxicity related to MX have been reported; however studies with longer follow-up (not included in this review) have raised concerns about the risk of systolic disfunction (˜12%) and therapy-related acute leukaemias (0.8%), which are increasingly reported in the literature.MX should be limited to treating patients with worsening RRMS and SPMS and with evidence of persistent inflammatory activity after a careful assessment of the individual patients' risk and benefit profiles. Assessment should also consider the present availability of alternative therapies with less severe adverse events.

Determinants of disability in multiple sclerosis at various disease stages: a multiparametric magnetic resonance study.

OBJECTIVE: To investigate whether diffusion-tensor magnetic resonance imaging and whole brain N-acetylaspartate (WBNAA) proton magnetic resonance spectroscopy can provide complementary pieces of information to achieve a better understanding of the factors associated with disability in multiple sclerosis (MS). DESIGN: Cross-sectional survey. SETTING: Referral hospital-based MS center. PATIENTS: Ten healthy control subjects, 27 patients with a clinically isolated neurological syndrome, 21 patients with relapsing-remitting MS, and 29 patients with secondary progressive MS. MAIN OUTCOME MEASURES: Conventional and diffusion-tensor magnetic resonance imaging, as well as WBNAA proton magnetic resonance spectroscopy, of the brain was performed. T2-hyperintense lesion volumes were measured. The mean values of mean diffusivity (MD) and fractional anisotropy of T2-visible lesions were computed. Histograms of MD and fractional anisotropy values were produced for normal-appearing white matter and gray matter (GM). RESULTS: Patients with a clinically isolated neurological syndrome had a significantly (P=.002) lower WBNAA concentration than control subjects. Patients with relapsing-remitting MS had significantly higher T2 lesion volume (P=.007), mean lesion MD (P=.003), normal-appearing white matter fractional anisotropy peak height (P=.03), and a lower WBNAA concentration (P<.001) than patients with a clinically isolated neurological syndrome. Patients with secondary progressive MS had significantly higher T2 lesion volume (P=.01), lower mean normal-appearing white matter fractional anisotropy (P=.003), higher mean GM MD (P=.004), and lower GM MD peak height (P=.01) than patients with relapsing-remitting MS. Disease duration, GM MD peak height, and WBNAA concentration entered a multivariate model, explaining nearly 70% of the disability variance. CONCLUSIONS: The accumulation of macroscopic lesions and normal-appearing white matter damage seems to occur mainly during the earliest clinical phases of MS, whereas pathological features of GM may be a hallmark of the late progressive stage of the disease. This supports the notion of MS as a "2-stage" disease.

Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis.

BACKGROUND: There is an increasing body of evidence that magnetic resonance imaging-occult tissue damage is an important component of primary progressive multiple sclerosis (PPMS) pathology. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure in vivo whole-brain N-acetylaspartate (WBNAA) concentrations, the decrease of whose levels is considered a marker of neuronal-axonal injury. OBJECTIVES: To study WBNAA 1H-MRS as a tool to provide information about irreversible brain damage in PPMS and to investigate the relationship between WBNAA and other magnetic resonance imaging measures of MS disease burden, including brain atrophy. METHODS: The following magnetic resonance pulse sequences of the brain were obtained from 32 patients with PPMS and 16 age-matched healthy subjects: (1) dual-echo turbo spin-echo; (2) T1-weighted spin-echo; and (3) 1H-MRS to measure WBNAA concentration. Brain total lesion volumes were measured. Normalized brain volumes were calculated using a fully automated technique. Absolute WBNAA amounts were calculated using a phantom replacement method and were then corrected for individual subjects' brain size. RESULTS: Levels of WBNAA concentrations and normalized brain volumes were significantly lower in patients with PPMS (mean values, 10.2 mm and 1500.0 mL, respectively) than in healthy controls (mean values, 12.9 mm and 1585.2 mL). Both WBNAA concentrations and normalized brain volumes were included as independent factors in the final model of a multivariable analysis predicting the subjects' condition. No significant correlations were found between WBNAA values and normalized brain volumes, WBNAA and T2-weighted or T1-weighted lesion volumes. CONCLUSIONS: Axonal-neuronal damage in the brain of patients with PPMS seems to occur, at least partially, independently of the burden of magnetic resonance imaging-visible lesions. Whole-brain N-acetylaspartate values and normalized brain volumes were unrelated in this cohort, thereby suggesting that 1H-MRS and atrophy assessment may provide in vivo complementary information about the actual extent of brain damage in PPMS.