Brain Atrophy and Physical and Cognitive Disability in Multiple Sclerosis.

Introduction: Brain atrophy is associated with physical disability in multiple sclerosis (MS), but there is a great variability between different studies and methodologies, and its use is still limited to research projects. We aimed to analyze the relationship between several volumetric measurements and physical disability and cognitive functioning in MS patients in a clinical practice setting. Methods: This is a cross-sectional study. A total of 41 patients (31 relapsing-remitting MS, 6 secondary-progressive MS, and 4 primary-progressive MS) were included. Whole brain volume (WBV), gray matter volume (GMV), and T2 lesion load (T2L) were obtained using Icometrix® software. Physical disability was measured with the Expanded Disability Status Scale (EDSS), and cognitive status was evaluated with the brief repeatable battery of neuropsychological tests (BRB-N). The relationship between brain volumes and EDSS was analyzed through linear multivariate regression. The association between volumetry measurements and the number of affected cognitive domains was studied with negative binomial regression. Results: GMV was associated with age (b=-1.7, P=0.014) and with EDSS (b=-7.55, P=0.013). T2L was associated with EDSS (b=2.29, P=0.032). The number of affected cognitive domains was associated with clinical phenotype, worse in primary progressive MS (PPMS). There was not correlations between cognitive impairment and cerebral volumes. Conclusion: Brain atrophy measurement is feasible in clinical practice setting, and it is helpful in monitoring the EDSS progression. Primary progressive phenotype is associated with greater risk of cognitive dysfunction. Highlights: The T2 lesion load is associated with physical disability in patients with multiple sclerosis (MS).The gray matter volume is associated with age and physical disability in patients with MS.There is no significant correlation between cognitive impairment and cerebral volumes in patients with MS. Plain Language Summary: Conventional magnetic resonance imaging (MRI) is still used for diagnosing and monitoring multiple sclerosis (MS). Analysis of Brain volumes including Whole brain volume (WBV), gray matter volume (GMV), and T2 lesion load (T2L) allows the evaluation of its neurodegenerative mechanisms. Robust evidence links brain atrophy with disability in MS. This study aims to analyze the relationship between advanced MRI sequences and physical disability and cognitive functioning in MS patients. According to the results, T2L was associated with physical disability and GMV was associated with age and physical disability. There was no significant correlation between cognitive impairment and cerebral volumes in patients with MS.

MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate.

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing-remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (ß = 0.23; 95% CI: 0.04-0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.

microRNA Expression and Its Association With Disability and Brain Atrophy in Multiple Sclerosis Patients Treated With Glatiramer Acetate.

Background: MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis. Objective: to correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis. Methods: cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant®. Results: We found an association between miR.146a.5p (rs:0.434, p=0.03) and miR.9.5p (rs:0.516, p=0.028) with EDSS; and miR-146a.5p (rs:-0.476, p=0.016) and miR-126.3p (rs:-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (rs:-0.545, p=0.036); miR.200c.3p with pallidum (rs:-0.68, p=0.002) and cerebellum (rs:-0.472, p=0.048); miR-138.5p with amygdala (rs:0.73, p=0.016) and pallidum (rs:0.64, p=0.048); and miR-223.3p with caudate (rs:0.46, p=0.04). Conclusions: These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis.

Older age, higher perceived disability and depressive symptoms predict the amount and severity of work-related difficulties in persons with multiple sclerosis.

Purpose: This cross-sectional study aims to identify the predictors of work-related difficulties in a sample of employed persons with multiple sclerosis as addressed with the Multiple Sclerosis Questionnaire for Job Difficulties. Materials and methods: Hierarchical linear regression analysis was conducted to identify predictors of work difficulties: predictors included demographic variables (age, formal education), disease duration and severity, perceived disability and psychological variables (cognitive dysfunction, depression and anxiety). The targets were the questionnaire's overall score and its six subscales. Results: A total of 177 participants (108 females, aged 21-63) were recruited. Age, perceived disability and depression were direct and significant predictors of the questionnaire total score, and the final model explained 43.7% of its variation. The models built on the questionnaire's subscales show that perceived disability and depression were direct and significant predictors of most of its subscales. Conclusions: Our results show that, among patients with multiple sclerosis, those who were older, with higher perceived disability and higher depression symptoms have more and more severe work-related difficulties. The Multiple Sclerosis Questionnaire for Job Difficulties can be fruitfully exploited to plan tailored actions to limit the likelihood of near-future job loss in persons of working age with multiple sclerosis. Implications for rehabilitation Difficulties with work are common among people with multiple sclerosis and are usually addressed in terms of unemployment or job loss. The Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific questionnaire developed to address the amount and severity of work-related difficulties. We found that work-related difficulties were associated to older age, higher perceived disability and depressive symptoms. Mental health issues and perceived disability should be consistently included in future research targeting work-related difficulties.

Determinants of mobility in populations of older adults: Results from a cross-sectional study in Finland, Poland and Spain.

OBJECTIVE: To identify the determinants of mobility among people aged 50+ from Finland, Spain and Poland. STUDY DESIGN: Observational cross-sectional population study. MAIN OUTCOME MEASURES: A mobility score was based on responses to items referring to body movements, walking, moving around and using transportation. Determinants of mobility were entered in hierarchical regression models in the following order: sociodemographic characteristics, health habits, chronic conditions, description of general state of health, vision and hearing, social networks, built environment. RESULTS: Complete data were available for 3902 participants (mean age 65.1, SD 9.8). The final model explained 64.7% of the variation in mobility. The most relevant predictors were: pain, age and living in Finland, presence of arthritis, stroke and diabetes, high-risk waist circumference, physical inactivity, and perceiving the neighborhood environment as more exploitable. CONCLUSIONS: Our results provide public health indications that could support concrete actions to address the modifiable determinants of mobility. These include the identification and treatment of pain-related problems, increasing the level of physical activity and the improvement of neighborhood features in terms of presence of general utility places or means of transportation. These factors can be modified with short- to medium-term interventions and such a change could improve the mobility of ageing population, with evident benefits for health.

Care pathways models and clinical outcomes in Disorders of consciousness.

OBJECTIVE: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care pathway for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients' clinical outcomes. MATERIALS AND METHODS: A multicenter observational pilot study was realized. Clinicians collected data on the care pathways of patients with Disorder of consciousness by asking 90 patients' caregivers to complete an ad hoc questionnaire through a structured phone interview. Questionnaire consisted of three sections: sociodemographic data, description of the care pathway done by the patient, and caregiver evaluation of health services and information received. RESULTS: Seventy-three patients were analyzed. Length of hospital stay was different across the health care models and it was associated with improvement in clinical diagnosis. In long-term care units, the diagnosis at admission and the number of caregivers available for each patient (median value = 3) showed an indirect relationship with worsening probability in clinical outcome. Caregivers reported that communication with professionals (42%) and the answer to the need of information were the most critical points in the acute phase, whereas presence of Non-Governmental Organizations (25%) and availability of psychologists for caregivers (21%) were often missing during long-term care. The 65% of caregivers reported they did not know the UN Convention on the Rights of Persons with Disabilities. CONCLUSION: This study highlights relevant differences in analyzed models, despite a recommended national pathway of care. Future public health considerations and actions are needed to guarantee equity and standardization of the care process in all European countries.

Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with Chronic Migraine: an effectiveness trial with a one-year follow-up.

BACKGROUND: Chronic Migraine (CM) is a disabling condition, worsened when associated with Medication Overuse (MO). Mindfulness is an emerging technique, effective in different pain conditions, but it has yet to be explored for CM-MO. We report the results of a study assessing a one-year course of patients' status, with the hypothesis that the effectiveness of a mindfulness-based approach would be similar to that of conventional prophylactic treatments. METHODS: Patients with CM-MO (code 1.3 and 8.2 of the International Classification of Headache Disorders-3Beta) completed a withdrawal program in a day hospital setting. After withdrawal, patients were either treated with Prophylactic Medications (Med-Group), or participated in a Mindfulness-based Training (MT-Group). MT consisted of 6 weekly sessions of guided mindfulness, with patients invited to practice 7-10 min per day. Headache diaries, the headache impact test (HIT-6), the migraine disability assessment (MIDAS), state and trait anxiety (STAI Y1-Y2), and the Beck Depression Inventory (BDI) were administered before withdrawal and at each follow-up (3, 6, 12 after withdrawal) to patients from both groups. Outcome variables were analyzed in separate two-way mixed ANOVAs (Group: Mindfulness vs. Pharmacology x Time: Baseline, 3-, 6-, vs. 12-month follow-up). RESULTS: A total of 44 patients participated in the study, with the average age being 44.5, average headache frequency/month was 20.5, and average monthly medication intake was 18.4 pills. Data revealed a similar improvement over time in both groups for Headache Frequency (approximately 6-8 days reduction), use of Medication (approximately 7 intakes reduction), MIDAS, HIT-6 (but only for the MED-Group), and BDI; no changes on state and trait anxiety were found. Both groups revealed significant and equivalent improvement with respect to what has become a classical endpoint in this area of research, i.e. 50% or more reduction of headaches compared to baseline, and the majority of patients in each condition no longer satisfied current criteria for CM. CONCLUSIONS: Taken as a whole, our results suggest that the longitudinal course of patients in the MT-Group, that were not prescribed medical prophylaxis, was substantially similar to that of patients who were administered medical prophylaxis.

Determinants of Quality of Life in Ageing Populations: Results from a Cross-Sectional Study in Finland, Poland and Spain.

PURPOSE: To comprehensively identify the determinants of quality of life (QoL) in a population study sample of persons aged 18-50 and 50+. METHODS: In this observational, cross-sectional study, QoL was measured with the WHOQOL-AGE, a brief instrument designed to measure QoL in older adults. Eight hierarchical regression models were performed to identify determinants of QoL. Variables were entered in the following order: Sociodemographic; Health Habits; Chronic Conditions; Health State description; Vision and Hearing; Social Networks; Built Environment. In the final model, significant variables were retained. The final model was re-run using data from the three countries separately. RESULTS: Complete data were available for 5639 participants, mean age 46.3 (SD 18.4). The final model accounted for 45% of QoL variation and the most relevant contribution was given by sociodemographic data (particularly age, education level and living in Finland: 17.9% explained QoL variation), chronic conditions (particularly depression: 4.6%) and a wide and rich social network (4.6%). Other determinants were presence of disabling pain, learning difficulties and visual problems, and living in usable house that is perceived as non-risky. Some variables were specifically associated to QoL in single countries: age in Poland, alcohol consumption in Spain, angina in Finland, depression in Spain, and self-reported sadness both in Finland and Poland, but not in Spain. Other were commonly associated to QoL: smoking status, bodily aches, being emotionally affected by health problems, good social network and home characteristics. CONCLUSIONS: Our results highlight the importance of modifiable determinants of QoL, and provide public health indications that could support concrete actions at country level. In particular, smoking cessation, increasing the level of physical activity, improving social network ties and applying universal design approach to houses and environmental infrastructures could potentially increase QoL of ageing population.