Sleep duration and mortality among breast cancer survivors in the Western New York Exposures and Breast Cancer (WEB) Study.

PURPOSE: There is increasing evidence that sleep duration may affect breast cancer survival through effects on circadian function, influencing disease progression. However, further investigation of this association is needed. METHODS: In a population-based, prospective cohort study of women from the Western New York Exposures and Breast Cancer Study, we examined mortality outcomes with invasive breast cancer identified using the National Death Index. Cox proportion hazards ratios with 95% confidence intervals were used to estimate risk of all-cause (AC) and breast cancer-specific (BC) mortality associated with self-reported usual sleep duration with adjustment for age, race/ethnicity, years of education, body mass index (BMI), menopausal status, pack-years of smoking, tumor stage, and estrogen-receptor (ER) status. We further examined associations within strata of BMI, tumor stage, menopausal status, and ER status. RESULTS: A sample of 817 patients with breast cancer were followed for a median of 18.7 years, during which 339 deaths were reported, including 132 breast cancer-specific deaths. Those who reported shorter or longer sleep tended to have a slightly higher BMI, to be less proportionately non-Hispanic White, to report a previous history of benign breast disease, and to have consumed more alcohol during their lifetime. We found no significant associations between sleep duration and AC or BC mortality, including within stratified analyses. CONCLUSION: Sleep duration was not associated with either AC or BC mortality including within strata of BMI, tumor stage, menopausal status, or ER status.

Patient-reported outcomes are the strongest predictors of disease disability in intramuscular interferon ß-1a users.

Introduction: Patient-reported outcomes (PROs) are valuable measures for routine clinical care of people with multiple sclerosis (pwMS). Materials: 646 pwMS treated with interferon-ß-1a (IFN-ß-1a) were retrospectively included from the New York State Multiple Sclerosis Consortium. Clinical and PRO data at enrollment and 3 year follow-up were collected. PwMS with stable disease and disability worsening were matched (1:1) based on age, Expanded Disability Status Scale (EDSS) scores and disease duration. Disability worsening was determined based on trial criteria. Results: PwMS with future EDSS worsening had higher baseline and follow-up timed-25-foot walk (6.6 vs 5.5 s; 9.1 vs 5.5 s; p < 0.001) when compared with stable pwMS. Worsening pwMS reported higher baseline difficulties in getting up (odds ratio [OR] = 2.4; p = 0.009), climbing stairs (OR = 1.6; p = 0.024) and standing (OR = 2.2; p < 0.001). Worsening pwMS reported greater lower limb limitations (OR = 2.3; p = 0.004) and fatigue (OR = 1.8; p = 0.002). Conclusion: Higher fatigue and lower limb functional limitations are significant predictors of future disability worsening in pwMS.

A large retrospective study was carried out on people with multiple sclerosis (PwMS) being treated with intramuscular interferon-ß medication from the New York State Multiple Sclerosis Consortium. The aim of the study was to look at whether patient-reported and clinical measures could be used early on to predict whether PwMS have worsening of their disease. The study demonstrated that patient-reported levels of limitations in multiple physical and mental symptoms can predict future worsening in objectively quantified disability in PwMS who take intramuscular interferon-ß medication. Reported limitations in lower extremities and fatigue were the most predictive of future disability worsening.

Patient-Reported Outcome Severity and Emotional Salience Network Disruption in Multiple Sclerosis.

BACKGROUND: Overall burden of white matter damage is associated with increased self-report fatigue severity in people with multiple sclerosis. However, a paradoxically opposite association was reported for white matter damage to tracts in specific subnetworks including the amygdala, temporal pole, and insula. Based on neuroanatomical principles and other data from the literature, we hypothesized that these results might be indicative of a broader relationship between damage to these subnetworks and impaired recognition of negative emotional salience central to patient-reported outcomes. OBJECTIVE: We examined whether damage in the same previously-identified subnetworks is also associated with lower self-report depressive symptoms, something which may be decreased in individuals with impaired recognition of negative emotional salience. Other patient characteristics were also explored. METHODS: In a cohort of 137 people with multiple sclerosis, we measured location-specific network white matter tract damage in the proposed negative emotional salience network, along with self-report severity of depressive symptoms and cognitive problems, personality characteristics, objective cognitive performance, and physical disability. We applied regression analyses, accounting for lesion burden, to explore the relationship between damage in the proposed negative emotional salience network and these factors. RESULTS: We found disruption within the negative emotional salience network is associated with lower self-report depressive symptoms (ß = -0.277, p = 0.036), cognitive complaints (r = -0.196, p = 0.024) and personality trait Neuroticism (r = -0.179, p = 0.042). In contrast, damage within this network was not significantly associated with objective cognitive processing speed, personality trait Openness, or physical disability. CONCLUSION: The identified network may be a generalizable network which corresponds to the recognition of negative emotional salience, but not to objective factors such as processing speed and physical disability. Damage to this network may paradoxically buffer against negative emotional perception of symptom severity, central to patient-reported outcomes.

Discontinuation of disease modifying therapies is associated with disability progression regardless of prior stable disease and age.

BACKGROUND: Multiple sclerosis (MS) patients with stable disease course might view continued treatment as unnecessary. However, guidelines regarding treatment discontinuation are currently lacking. OBJECTIVE: To assess the clinical course after treatment discontinuation in MS patients with long disease duration. METHODS: Patients who discontinued disease-modifying treatments (DMTs) and not resume treatment (n = 216) were extracted from New York State MS Consortium (NYSMSC) and followed across three time points (average 4.6 years). Stable course was defined as no change in Expanded Disability Status Scale (EDSS) scores (<1.0 increase if EDSS<6.0 or <0.5-point increase if EDSS≥6.0) from baseline (time 1) to DMT discontinuation (time 2). Both stable and worsening MS patients were later assessed again after the DMT discontinuation (time 3). Additional analyses were performed based on disease subtype, type of medication, age cut-off of 55 and EDSS of 6.0. RESULTS: From the cohort of 216 MS patients who discontinued DMT, 161 (72.5%) were classified as stable before DMT discontinuation. After DMT discontinuation, 53 previously stable MS patients (32.9%) experienced disability worsening/progression (DWP). 29.2 and 40% of previously stable RRMS and SPMS respectively had DWP after DMT discontinuation. Over two years after DMT discontinuation, the rate of DWP was similar between patients younger or older than 55 years (31.1% vs 25.9%, respectively). MS patients with EDSS≥6.0 had greater DWP when compared to less disabled patients while remaining on therapy as well as after discontinuation (40.7% vs 15.4%, p < 0.001 and 39.6% vs 15.2%, p < 0.001, respectively). CONCLUSION: MS patients with stable disease course experience DWP after treatment discontinuation, with no clear relation to age and disease subtype. Patients with EDSS≥6.0 are at higher risk for DWP.

Clinical effects associated with five-year retinal nerve fiber layer thinning in multiple sclerosis.

BACKGROUND: Neurodegenerative changes in multiple sclerosis (MS) are associated with long-term disability progression (DP). Optical coherence tomography (OCT) measures may be used to monitor DP. OBJECTIVE: To determine significant effects driving the changes in OCT-based peripapillary retinal nerve fiber layer (pRNFL) in heterogeneous group of MS patients. METHODS: Total of 144 MS patients (109 relapsing-remitting MS and 35 progressive MS (PMS) with mean age at baseline of 47.6 and 56.5 years old, respectively) underwent clinical and OCT examination over 5-year follow-up. All OCT exams were reviewed using the OSCAR-IB criteria. The 5-year DP was determined based on Expanded Disability Status Scale (EDSS) changes and MS clinical trial criteria. Data regarding previous history of MS optic neuritis (MSON) and use of disease modifying treatment (DMT) was derived by in-person interview and review of electronic medical records. Mixed model-type of repeated measure analysis determined effects driving pRNFL change for analysis which utilized all eyes separately. RESULTS: Over an average of 5.3-years follow-up, the MS population demonstrated significant pRNFL thinning (F = 16.108, p < 0.001). The pRNFL thinning was greater due to progressive MS subtype (F = 5.102, p = 0.025), greater age at baseline (F = 4.554, p = 0.034), occurrence of DP (F = 6.583, p = 0.011), and previous history of MSON (F = 7.053, p = 0.008). Use of any or highly potent DMT (natalizumab versus first-line injectable treatments versus no DMT) significantly reduced the pRNFL thinning (F = 8.367, p = 0.004) over the follow-up. Lastly, occurrence of DP in PMS patients older than 50 years old was associated with greater pRNFL thinning (F = 6.667, p = 0.013). CONCLUSION: Longitudinal pRNFL changes are modified by age, disease subtype, disabiltiy progression, history of MSON, DMT use and their interactions.

Safety and efficacy of antiplatelet use before intravenous thrombolysis for acute Ischemic stroke.

AIM: To study the effects of pretreatment with Antiplatelet (AP) before IV thrombolysis (IVT) on the rate of symptomatic intracranial hemorrhage (sICH) and functional outcome in patients with Acute Ischemic stroke (AIS). METHOD: In this retrospective study, the medical records and cerebrovascular images of all the patients who received IVT for AIS in our center in a 9.6-year period were reviewed. Patients who took at least one dose of any APs in the last 24 h prior to IVT were identified. They were categorized according to the type of AP, single versus dual AP therapy (DAPT), and dose of AP. Rate of sICH and functional outcome at discharge were compared between the AP users and non-users. RESULTS: A total of 834 patients received IVT for AIS in our center during a 9.6- year period. Multivariate models were adjusted for age, NIHSS on admission, history of atrial fibrillation, history of hypertension, INR on admission, history of stroke and diabetes mellitus. In multivariate regression analyses and after adjusting for the variables mentioned above, the use of any AP was not associated with an increased rate of sICH (OR = 1.28 [0.70-2.34], p = 0.425). Furthermore, the use of DAPT did not significantly increase the rate of sICH in multivariate regression analyses. (OR = 0.663 [0.15-2.84], p = 0.580). The patients on any AP had a lower chance of having good functional outcome in univariate analysis (OR = 0.735 [0.552-0.979], p = 0.035). However, when adjusted for age, baseline NIHSS, history of diabetes, hypertension and prior stroke, AP use was not associated with a decreased chance of having a good functional outcome at discharge. (OR = 0.967 [0.690-1.357], p = 0.848). In addition, no significant difference was noted in the rate of good functional outcome between patients on DAPT and no AP users in multivariate regression analyses. (OR = 1.174 [0.612-2.253], p = 0.629). CONCLUSION: Our study did not show any significant association between the risk of sICH and good functional outcome after IVT for AIS patients on AP therapy (dual or single) in comparison with AP naïve patients.

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR.

INTRODUCTION: Current guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. METHODS: Patients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. RESULTS: No significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. CONCLUSION: Administration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.

Does Body Mass Index Impact the Outcome of Stroke Patients Who Received Intravenous Thrombolysis?

BACKGROUND: We sought to investigate the effect of obesity and BMI on functional outcome and rate of symptomatic intracranial hemorrhage (sICH) in a large sample of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS: In a single-center retrospective, but prospectively collected data, study of patients with AIS treated with IVT in a 10-year period, patients were placed into groups based on their BMI defined as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (<30 kg/m2). The rate of sICH and discharge modified Rankin Scale (mRS) were compared between the groups using logistic regression analysis. RESULTS: In a total of 834 patients who received IVT for AIS during a 10-year period, 224 (27.0%) were obese. Obese patients did not have a higher rate of sICH after IVT for AIS on the unadjusted or adjusted analysis (adjusted OR 0.95, 95% CI 0.48-1.88). We did not find an association between obesity and poor functional outcome at discharge (adjusted OR 0.76, 95% CI 0.53-1.09). CONCLUSIONS: After adjusting for confounding factors such as age, baseline National Institute of Health Stroke Scale (NIHSS), and comorbidities, obesity was not associated with an unfavorable functional outcome at discharge nor with a higher risk of sICH in patients with AIS treated with IVT.

Diagnosis of depression in multiple sclerosis is predicted by frontal-parietal white matter tract disruption.

BACKGROUND: Persons with multiple sclerosis (PwMS) are at an elevated risk of depression. Decreased Conscientiousness may affect patient outcomes in PwMS. Low Conscientiousness has a strong correlation with depression. Previous work has also reported that white matter (WM) tract disruption in frontal-parietal networks explains reduced Conscientiousness in PwMS. OBJECTIVE: We hypothesized that Conscientiousness-associated WM tract disruption predicts new-onset depression over 5 years in PwMS and evaluated this by assessing the predictive power of mean Conscientiousness associated frontal-parietal network (CFPN) disruption in PwMS for clinically diagnosed depression over 5 years. METHODS: This longitudinal retrospective analysis included 53 PwMS who were not previously diagnosed as depressed. All participants underwent structural MRI. Medical records were reviewed to evaluate diagnosis of depression for these patients over 5 years. WM tract damage between pairs of gray matter regions in the CFPN was measured using diffusion imaging. The relationship between CFPN disruption and depression was analyzed using logistic regression. RESULTS: Participants with MS had a mean age of 46.0 years (SD = 11.2). 22.6% (n = 12) acquired a diagnosis of clinical depression over the 5-year period. Baseline disruption in the CFPN was a significant predictor (ROC AUC = 61.8%). of new-onset clinical depression, accounting for age, sex, lateral ventricular volume, disease modifying treatment, and lesion volume. CONCLUSION: Baseline CFPN disruption is associated with progression to clinical depression over 5 years in PwMS. Development of new WM pathology within this network may be a risk factor for depression.

Statins Use and Outcome of Acute Ischemic Stroke Patients after Systemic Thrombolysis.

AIM: The aim of this was to study the effects of statins and their intensity on symptomatic intracranial hemorrhage (sICH) and outcome after IV thrombolysis (IVT) for acute ischemic stroke (AIS). METHODS: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with IVT for AIS in our center in a 10-year period. Patients were further characterized as any statin users versus non-users on admission to the emergency department. Statins were categorized in high intensity or low intensity statin based on its propensity to reduce lower low-density cholesterol by ≥45% or <45%, respectively. Safety and discharge modified Rankin Score were compared between statin users versus non-users and also between high-intensity versus low-intensity groups. RESULTS: A total of 834 patients received IVT for AIS in our center during a 10-year period. Multivariate models were adjusted for age, NIH Stroke Scale at admission, INR, and history of DM and atrial fibrillation. There was no association between odds of sICH and any statin use (OR = 0.52 [0.26-1.03], p = 0.06). In multivariate model, any statin use was not associated with odds of poor outcome (Table 4: OR = 1.01 [0.79-1.55], p = 0.57). There was no significant association between odds of sICH among patients on high-intensity statin compared to low intensity statin (multivariate model OR = 0.39 [0.11-1.40], p = 0.15). There was 47% reduced odds of poor outcome among patients on high-intensity statin as compared to low-intensity statin (OR = 0.53[0.32-0.88] p = 0.01). However, this significant association was lost in the multivariate model (OR = 0.60 [0.35-1.05], p = 0.07). CONCLUSION: Our study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy. We also did not find significant association between the risk of sICH and poor outcome after IVT and the intensity of the stain used.

Safety and Tolerability of 3 CGRP Monoclonal Antibodies in Practice: A Retrospective Cohort Study.

OBJECTIVE: We sought to assess the safety and tolerability of 3 calcitonin gene-related peptide (CGRP) monoclonal antibodies in patients with chronic migraine who have failed multiple classes of migraine preventive therapies. BACKGROUND: CGRP is an important neuromodulator implicated in the pathogenesis of migraine. They are approved for the treatment of episodic and chronic migraine. In current clinical practice, CGRP monoclonal antibodies are used in patients who have failed multiple preventive agents, but safety, tolerability, and efficacy have not been well described in real-world populations outside of clinical trials. METHODS: This was a single-center, observational, retrospective study in adults with chronic migraine treated with a CGRP monoclonal antibody between May 1, 2018 and September 30, 2019. Charts were reviewed at 0, 3, and 6 months after treatment. RESULTS: From May 1, 2018 to September 30, 2019, 77 patients with chronic migraine were prescribed 90 treatment trials of a CGRP monoclonal antibody. Patients reported adverse outcomes in 2/5 (40.0%) with erenumab 70 mg, 32/46 (69.6%) with erenumab 140 mg, 8/16 (50.0%) with fremanezumab, and 15/23 (65.2%) with galcanezumab. The most frequent adverse effects were constipation and injection site reactions. Adverse effects leading to discontinuation were reported as follows: erenumab 70 mg 1/5 (20.0%), erenumab 140 mg 10/46 (22.7%), fremanezumab 1/16 (6.3%), and galcanezumab 1/23 (4.3%), with 13/90 (14.4%) discontinuation rate overall. The most frequent reasons for discontinuation were lack of improvement in 17/90 (18.9%) and constipation in 4/90 (4.4%). A 50% or greater reduction in the number of severe headache days per month was achieved for 32/66 (48.5%) at 3 months and 17/48 (35.4%) at 6 months. CONCLUSIONS: In patients with chronic migraine, the 3 CGRP monoclonal antibodies were well tolerated, and reduced the number of severe headache days.

Long-term drug treatment in multiple sclerosis: safety success and concerns.

INTRODUCTION: The portfolio of multiple sclerosis (MS) disease modifying treatments (DMTs) has significantly expanded over the past two decades. Given the lifelong use of MS pharmacotherapy, understanding their long-term safety profiles is essential in determining suitable and personalized treatment. AREAS COVERED: In this narrative review, we summarize the short-, mid-, and long-term safety profile of currently available MS DMTs categories. In addition to the initial trial findings, safety outcomes derived from long-term extension studies (≥5-20 years) and safety-based prescription programs have been reviewed. In order to better understand the risk-benefit ratio for each particular DMT group, a short description of the DMT-based efficacy outcomes has been included. EXPERT OPINION: Long-term extension trials, large observational studies and real-world databases allow detection of rare and potentially serious adverse events. Two-year-long trials are unable to fully capture the positive and negative effects of immune system modulation and reconstitution. DMT-based monitoring programs can provide greater insights regarding safe use of MS medications in different patient populations and clinical settings. During the process of shared DMT decision, both MS care providers and their patients should be aware of an ever-expanding number of drug-based adverse events and their influence on the risk-benefit analysis.

Tonsillectomy in multiple sclerosis patients: Retrospective, case-controlled, exploratory study.

BACKGROUND: Previous studies have shown an effect of tonsillectomy and greater risk for future autoimmune diseases. Currently there are only few outdated analyses of tonsillectomy and multiple sclerosis (MS) risk. OBJECTIVE: To investigate the prevalence of tonsillectomy in MS patients and healthy controls (HCs). METHODS: A total of 1000 subjects (779 MS patients and 221 HCs) completed a structured study questionnaire regarding MS diagnosis, age of onset, history of tonsillectomy, and age of tonsillectomy. In a subgroup of patients with available electronic medical records, Expanded Disability Status Scale (EDSS) scores at the time of recruitment and 5-years later were collected. Statistical analyses were performed with χ2 test, odds ratio (OR), Student's t-test, Mann-Whitney U test, and ordinal regression.. RESULTS: The MS population had a greater percentage of patients with history of tonsillectomy when compared to HCs [39.5% vs. 31.7%, OR 1.411 (CI 1.027-1.938), p = 0.034], driven by participants aged 50 or older [45.7% vs. 36.1%, OR 1.495 (CI 1.037-2.155) p = 0.031]. There was no difference of the age at tonsillectomy (median 8.0 vs. 6.5 years old, p = 0.26). However, the RRMS patients had their tonsillectomy procedure performed significantly later when compared to HCs (median 6.5 vs. 9.0 years old, p = 0.049). In an analysis of RRMS patients with available longitudinal data (n = 459), patients with a history of tonsillectomy were significantly older and had a longer disease duration (p < 0.001 and p = 0.025). After adjusting for the demographic differences, no history of tonsillectomy remained significant predictor of lower EDSS score categories both at the first (estimate = -0.467, Wald = 6.68, 95% CI -0.82 to -0.11, p = 0.01) and second timepoint (estimate = -0.376, Wald = 4.4, 95% CI -0.73 to -0.02 p = 0.037). CONCLUSION: When compared to HCs, a greater percentage of MS patients underwent tonsillectomy. The role of tonsils, its relationship with early infection rates and/or antibiotic use in MS should be further investigated.

Fatigue at enrollment predicts EDSS worsening in the New York State Multiple Sclerosis Consortium.

BACKGROUND: Fatigue is one of the most common and distressing symptoms among persons with multiple sclerosis (pwMS). OBJECTIVE: The aim of this study is to evaluate fatigue as a predictor for disease worsening among pwMS. METHODS: In this retrospective cohort study of New York State MS Consortium (NYSMSC) registry, MS patients reporting moderate-to-severe fatigue at study enrollment (n = 2714) were frequency matched to less-fatigued subjects (n = 2714) on age, baseline Kurtzke Expanded Disability Status Scale (EDSS), disease duration, and MS phenotype. Change from baseline patient-reported outcomes (PROs), as measured by LIFEware™, categorized participants into two groups: those with stable/improved outcomes and those who worsened. In a subgroup of patients with longitudinal data (n = 1951), sustained EDSS worsening was analyzed using Cox proportional hazards modeling to explore the effect of fatigue. RESULTS: The median survival time from study enrollment to sustained EDSS worsening was 8.7 years (CI: 7.2-10.1). Participants who reported fatigue at baseline were more likely to experience sustained EDSS worsening during follow-up (HR: 1.4, 95% CI: 1.2-1.7). Patients who were fatigued at baseline were also more likely to report worsening psychosocial limitations (all ps ⩽ 0.01). CONCLUSION: In addition to being a common symptom of MS, severe fatigue was a significant predictor for EDSS worsening in the NYSMSC.

Dimethyl Fumarate in the Treatment of Relapsing-Remitting Multiple Sclerosis: Patient Reported Outcomes and Perspectives.

Dimethyl fumarate (DMF) is a commonly prescribed oral medication for the treatment of relapsing forms of multiple sclerosis (MS) with a wide range of hypothesized downstream mechanisms of action. Randomized clinical trials have established its clinical efficacy by using standard objective clinical measures. However, MS is a chronic disease that, apart from physical ailments, can affect an individual's mood, psychosocial status, and quality of life which cannot be captured by using only objective assessment tools. Given the challenge of determining the efficacy of the treatment in a real-world clinical setting, the use of patient-reported outcomes (PROs) may help us to better address these aspects of patient care and establish a more patient-centered approach to MS care. To date, a review of PubMed identified six studies which reported on PROs in patients who are taking DMF. In total, twelve different kinds of PRO measures were utilized and 6359 patients provided at least one form of PRO in these studies. Upon review of these studies, we were able to conclude that people with MS had decreased quality of life compared to the healthy population in the US. MS patients on DMF, however, had better health-related quality of life assessment scores compared to those using a placebo. Previous studies also suggested that DMF decreased work productivity impairment scores after one year of use compared to baseline. DMF was associated with less impairment in fatigue and depression scales along with improved treatment quality assessment and adherence scores. This review will present a brief synopsis of the published literature and will provide indications for future directions with respect to PROs and DMF in people with MS.

Epidemiology and treatment of multiple sclerosis in elderly populations.

The prevalence of multiple sclerosis (MS) and the age of affected patients are increasing owing to increased longevity of the general population and the availability of effective disease-modifying therapies. However, ageing presents unique challenges in patients with MS largely as a result of their increased frequency of age-related and MS-related comorbidities as well as transition of the disease course from an inflammatory to a neurodegenerative phenotype. Immunosenescence (the weakening of the immune system associated with natural ageing) might be at least partly responsible for this transition, which further complicates disease management. Currently approved therapies for MS are effective in preventing relapse but are not as effective in preventing the accumulation of disability associated with ageing and disease progression. Thus, ageing patients with MS represent a uniquely challenging population that is currently underserved by existing therapeutic regimens. This Review focuses on the epidemiology of MS in ageing patients. Unique considerations relevant to this population are discussed, including the immunology and pathobiology of the complex relationship between ageing and MS, the safety and efficacy of disease-modifying therapies, when discontinuation of treatment might be appropriate and the important role of approaches to support wellness and cognition.

Altered nuclei-specific thalamic functional connectivity patterns in multiple sclerosis and their associations with fatigue and cognition.

BACKGROUND: The thalamus, affected early in multiple sclerosis (MS), is a heterogeneous composition of functionally distinct nuclei and is associated with fatigue, cognition, and other outcomes. However, most previous functional imaging studies considered the thalamus only as a whole. OBJECTIVE: To investigate MS-related abnormalities in nuclei-specific thalamic functional connectivity (FC) and their associations with fatigue and cognitive outcomes. METHODS: Resting-state functional magnetic resonance imaging (fMRI) was analyzed in 64 MS patients and 26 healthy controls (HC). Whole-brain FC maps for four thalamic subregions seeds were computed for each subject. FC maps were compared between groups, and group by FC interaction effects were assessed for fatigue and cognitive measures. RESULTS: MS patients had decreased FC between the left medial thalamic nuclei and left angular gyrus and reduced FC between the left posterior thalamic nuclei and left supramarginal gyrus, as well as decreased right medial thalamic nuclei connectivity with bilateral caudate/thalamus and left cerebellar areas (p < 0.05 corrected). MS patients had increased FC between the left anterior thalamic nuclei and anterior cingulate cortex bilaterally. There were significant relationships between connectivity alterations and fatigue and cognitive measures between groups (p < 0.05 corrected). CONCLUSION: FC alteration is nuclei-specific and is differentially associated with fatigue and cognition.

Lower self-report fatigue in multiple sclerosis is associated with localized white matter tract disruption between amygdala, temporal pole, insula, and other connected structures.

BACKGROUND: Fatigue, a frequent and disabling symptom for people with multiple sclerosis (PwMS), inconsistently correlates with white matter (WM) pathology. Network-based analysis, accounting for the manner in which lesions disrupt networks of structurally connected gray matter (GM) regions, may provide additional insight. OBJECTIVE: To identify patterns of WM tract disruption which explain self-reported fatigue severity in PwMS. METHODS: 137 PwMS and 50 age- and sex-matched healthy controls (HC) underwent fatigue assessment and brain MRI. Lesion maps were applied to determine the severity of WM tract disruption between pairs of GM regions. Then, the Network-Based-Statistics tool was applied to identify structural networks whose disruption explained fatigue severity. To determine whether these networks explain unique variance above conventional MRI measures and depression, regressions were applied controlling for age, sex, brain volume, T2-lesion volume, and depression. RESULTS: Patient-perceived fatigue in PwMS was positively associated with overall lesion burden (ß = 0.563, p-value < 0.001). In contrast, localized disruptions in WM tracts between regions including the amygdala, insula, hippocampus, putamen, temporal pole, caudal-middle-frontal gyrus, rostral-middle-frontal gyrus, inferior-parietal gyrus, and banks of the superior temporal sulcus were significantly negatively correlated with fatigue in PwMS (ß = -0.586, p-value < 0.001). Average disruption within this specific, localized network explained significant additional variance in fatigue above what was otherwise explained by depression and conventional MRI measures of neuropathology (ΔR2 = 0.078, p-value < 0.001). CONCLUSION: Although overall lesion burden correlates positively with fatigue in PwMS, localized WM damage between the amygdala, temporal pole, and other connected structures is associated with lower severity of patient-perceived fatigue.

Walking disability measures in multiple sclerosis patients: Correlations with MRI-derived global and microstructural damage.

BACKGROUND: The relationship between walking disability in multiple sclerosis (MS) patients and their macro- and microstructural MRI-derived measures still remains unclear. OBJECTIVE: To assess the correlations between walking disability and MRI-derived lesion, atrophy, and microstructural/axonal integrity outcomes. METHODS: Seventy-one (71) MS patients were clinically examined, the expanded timed get-up and go (ETGUG), and timed 25-foot walk (T25FW) tests were assessed. Additionally, the Symbol Digit Modalities Test (SDMT) was obtained. Normalized brain (NBV), gray matter (GMV), white matter (WMV), cortex (CV), and deep GM (DGM) volumes, as well as lesion volumes (LV) and diffusion tensor imaging (DTI) scalar maps of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated. Spearman correlation, partial correlation and stepwise regression analyses were performed. RESULTS: T25FW and ETGUG were associated with T2-LV (p < .001), global (NBV, p < .001), tissue-specific (GMV and CV, p < .001) and regional (DGM p < .001; and thalamus p < .001) volumes. The ETGUG remained correlated with T1-LV, GMV, CV and total DGM volume (all p < .001) after age, sex, and disease duration adjustment. The WMV was not associated with walking disability. Similarly, DTI measures did not show significant association with the walking tests. The regression analysis outlined DMG volume as best predictor of T25FW (Adj R2 = 0.231, standardized ß = -0.435, and p = .001), and CV for ETGUG (Adj R2 = 0.176, standardized ß = -0.417, and p = .004). SDMT was associated with both T25FW (p = .004) and ETGUG (p = .013). CONCLUSION: Despite the low disability levels, walking as measured by T25FW and ETGUG, is largely explained by the loss of cortical and nuclei specific GM volumes.

An Update on the Use of Disease-Modifying Therapy in Pregnant Patients with Multiple Sclerosis.

The active management of multiple sclerosis (MS) has been made possible during the last two decades with the advent of disease-modifying therapies (DMTs), leading to improved clinical outcomes for many patients. Furthermore, with the realization that MS does not adversely affect pregnancy outcome and that pregnancy does not have an overall negative impact on the long-term disease course of MS, the importance of appropriate counseling and discussion of future pregnancy plans with women of childbearing age is greater than ever. Although several DMTs are licensed for the treatment of MS, none are specifically approved for use during pregnancy or breastfeeding and the use of DMTs during these periods frequently gives rise to concerns regarding potential risks to the fetus. The outcomes of studies in patients with MS treated with DMTs during pregnancy and immediately postpartum have been the focus of several recently published papers. Given the high level of interest surrounding the prescribing of DMTs for MS patients of childbearing age, and the lack of clear guidance in this respect, the current review presents an up-to-date overview of new data, including observational data on real-world outcomes, that have been published during the last 2 years, and could inform future prescribing decisions.