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Background: Cognitive impairment is a prominent feature of multiple sclerosis (MS). However, the impact that cognitive symptoms have on daily life, and the effect this has on persons with MS and their relationships with spouses/partners, remains unclear. This qualitative study sought information on the nature of cognitive impairments experienced and the impact of cognitive impairments on the daily lives of adults with MS and their partners to gain further insights into how health care professionals can best support families. Methods: Fifteen persons with MS and their spouses/partners participated in separate semistructured telephone interviews. Results: Six themes and several subthemes were identified: the social impact of cognitive impairments in MS, changes to daily living, relationship quality, communication, ways of coping with MS, and the desire for help in managing MS. Conclusions: These results identified types of support that couples needed and wanted; ways that MS affects couples’ social lives; that there are difficulties negotiating changes in roles due to cognitive challenges; that there are difficulties coping with the impact of cognitive challenges on daily living; that couples often have difficulty communicating about the impact of cognitive changes on daily living and related issues, which also contributes to relationship strain; and finally, that most participants felt that they did not understand enough about the cognitive symptoms of MS. We outline key areas to address these identified needs.

Objective: The efficacy and safety of ocrelizumab, versus interferon (IFN) β-1a, for the treatment of relapsing multiple sclerosis (RMS) from the identically designed OPERA I (NCT01247324) and OPERA II (NCT01412333) phase III studies has been reported; here we present subgroup analyses of efficacy endpoints from the pooled OPERA I and OPERA II populations. Methods: Patients with RMS were randomized to either ocrelizumab 600 mg administered by intravenous infusion every 24 weeks or subcutaneous IFN β-1a 44 µg three times per week throughout the 96-week treatment period. Relapse, disability, and MRI outcomes were analyzed for predefined and post hoc subgroups based on demographic and disease characteristics along with prior treatment using appropriate statistical tests to determine the treatment effect in subgroups and treatment-by-subgroup interactions. Results: The significant treatment benefit of ocrelizumab, versus IFN β-1a, observed in the overall OPERA I and OPERA II pooled populations was maintained across most subgroup strata for all endpoints, including annualized relapse rate, disability progression, and MRI outputs. Conclusions: The treatment effect of ocrelizumab versus IFN β-1a, measured by clinical and MRI outcomes, was maintained across most of the subgroups and strata of interest, and the pattern of treatment benefit across all subgroups was consistent with that from the pooled OPERA studies.

Background Resilience is a protective factor that emerges when individuals are faced with challenges and stressors. Multiple sclerosis (MS) is a chronic neurological disease that introduces a great deal of stress for the individual and his/her support partner. We designed a telehealth resilience-building dyadic program for persons with MS (PwMS) and their support partners. Objectives To evaluate the feasibility of the resilience intervention. The secondary objective was to assess the benefits of the intervention. Methods Sixty-two participants ( M = 49.5 years, 31 dyads of PwMS) and support partners) were recruited to participate. Out of the 31 dyads, 26 were spouses, 2 were cohabiting partners, and 3 were parent–child dyads. Results The feasibility goals of the intervention were met, as determined by high participant satisfaction and acceptable completion rates. Preliminary outcomes relating to resilience were positive, suggesting that this intervention had a positive impact on participants. Conclusions To the best of our knowledge, this is the first resilience-building intervention delivered via telehealth for both PwMS and their support partners. The study showed an increase in resilience-building skills for addressing the challenges faced by PwMS and their support partners. These skills can be promoted and taught, clinically supported by telehealth, an affordable, accessible healthcare solution. Trial Registration at ClinicalTrials.gov (NCT03555253).

Mucopolysaccharidosis type II is a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS) and characterized by the accumulation of the primary storage substrate, glycosaminoglycans (GAGs). Understanding central nervous system (CNS) pathophysiology in neuronopathic MPS II (nMPS II) has been hindered by the lack of CNS biomarkers. Characterization of fluid biomarkers has been largely focused on evaluating GAGs in cerebrospinal fluid (CSF) and the periphery, however, GAG levels alone do not accurately reflect the broad cellular dysfunction in the brains of MPS II patients. We utilized a preclinical mouse model of MPS II, treated with a brain penetrant form of IDS (ETV:IDS) to establish the relationship between markers of primary storage and downstream pathway biomarkers in the brain and CSF. We extended the characterization of pathway and neurodegeneration biomarkers to nMPS II patient samples. In addition to the accumulation of CSF GAGs, nMPS II patients show elevated levels of lysosomal lipids, neurofilament light chain, and other biomarkers of neuronal damage and degeneration. Furthermore, we find that these biomarkers of downstream pathology are tightly correlated with heparan sulfate. Exploration of the responsiveness of not only CSF GAGs but also pathway and disease-relevant biomarkers during drug development will be crucial for monitoring disease progression, and the development of effective therapies for nMPS II.

Background: Upper extremity (UE) impairment is common with primary progressive multiple sclerosis (PPMS). Objective: This exploratory analysis examined the effects of ocrelizumab on confirmed progression (CP) and confirmed improvement (CI) in UE impairment in patients from ORATORIO. Methods: Patients with PPMS received ocrelizumab 600 mg or placebo every 24 weeks for ⩾120 weeks. The Nine-Hole Peg Test (9HPT) was administered at baseline (BL) and every 12 weeks thereafter. Prespecified exploratory endpoints included change in 9HPT time and proportion of patients with CP of ⩾20% in 9HPT. Analysis populations included intention-to-treat (ITT) patients and subgroups stratified by BL 9HPT time and Expanded Disability Status Scale. Post hoc analyses included the proportion of patients achieving more severe thresholds of CP and the proportion achieving CI in 9HPT. Results: Among ITT patients, ocrelizumab significantly reduced the change in 9HPT time over 120 weeks, the risk of CP of ⩾20% in 9HPT time for both hands and the risk of more severe 9HPT progression versus placebo. Numerical trends also favoured ocrelizumab versus placebo with respect to achieving CI. Consistent directional trends were observed in subgroup analyses. Conclusion: Ocrelizumab reduces the risk of UE disability progression and may increase the possibility of improvement versus placebo in PPMS.

Background Subcutaneous peginterferon beta-1a has previously been shown to reduce the number of T2-hyperintense and gadolinium-enhancing (Gd+) lesions over 2 years in patients with relapsing-remitting multiple sclerosis (RRMS), and to reduce T1-hypointense lesion formation and the proportion of patients showing evidence of disease activity, based on both clinical and radiological measures, compared with placebo over 1 year of treatment. The objectives of the current analyses were to evaluate T1 lesions and other magnetic resonance imaging (MRI) measures, including whole brain volume and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT), and the proportions of patients with no evidence of disease activity (NEDA), over 2 years. Methods Patients enrolled in the ADVANCE study received continuous peginterferon beta-1a every 2 or 4 weeks for 2 years, or delayed treatment (placebo in Year 1; peginterferon beta-1a every 2 or 4 weeks in Year 2). MRI scans were performed at baseline and Weeks 24, 48, and 96. Proportions of patients with NEDA were calculated based on radiological criteria (absence of Gd + and new/newly-enlarging T2 lesions) and clinical criteria (no relapse or confirmed disability progression) separately and overall. Results Peginterferon beta-1a every 2 weeks significantly reduced the number and volume of T1-hypointense lesions compared with delayed treatment over 2 years. Changes in whole brain volume and MTR of NABT were suggestive of pseudoatrophy during the first 6 months of peginterferon beta-1a treatment, which subsequently began to resolve. Significantly more patients in the peginterferon beta-1a every 2 weeks group compared with the delayed treatment group met MRI-NEDA criteria (41% vs 21%; odds ratio [OR] 2.56; p

IntroductionBrain volume loss (BVL) occurs in multiple sclerosis (MS) patients, reflecting irreversible tissue damage. No evidence of disease activity (NEDA), a composite measure assessing absence of clinical and magnetic resonance imaging (MRI) disease activity has emerged as important treatment goal in MS and may be associated with preservation of brain tissue and BVL prevention.MethodsPatients in OPERA-I/II (NCT01247324/NCT01412333) received 600 mg ocrelizumab (intravenous) very 24 weeks or 44 µg subcutaneous interferon beta-1a (IFNβ-1a) 3x-weekly for 96 weeks. Brain MRI assessments were completed at baseline and 24/48/96 Weeks. Brain volume normalised for head size was measured using SIENAX software. Percent change in whole brain volume (WBV) was determined using SIENA software, changes in cortical grey (GMV) and white (WMV) matter volumes were measured using validated, locally developed Jacobian integrator atrophy software. NEDA was defined as absence of relapses, 12-week confirmed disability progression, T1 Gd–enhancing lesions and new and/or enlarging T2-lesions. Changes from baseline in brain volume were examined in NEDA patients and those with evidence of disease activity (EDA), using the mixed-effects model for repeated measures method.ResultsThe analysis included 1520 patients (ocrelizumab-761; IFNβ-1a-759). Over 96 weeks, 569 (37%) patients [ocrelizumab-363 (48%); IFNβ-1a-206(27%); pConclusionThese findings highlight the importance of NEDA as treatment goal with respect to brain tissue preservation regardless of treatment choice. Ocrelizumab may confer additional benefits in NEDA patients NEDA beyond what is observed with IFNβ-1a.

IntroductionUpper limb (UL) functional impairment is prevalent among PPMS patients and alters quality of life. The nine-hole peg test (9HPT) is a validated quantitative assessment of UL function in MS.Methods9HPT was administered at baseline and every 12 weeks until study end. The average 9HPT-times from two trials of dominant- and non-dominant-hands were compared; the hand with the lower baseline time was termed ‘better-hand’, and the hand with the higher baseline time was termed ‘worse-hand’. Average dominant- and non-dominant-hand times were combined and termed ‘both-hands’. Analyses included time-to-confirmed progression (CP) in hand function, defined as ≥15%, ≥20% or ≥25% increase in 9HPT-time from baseline, confirmed at 12- and 24 weeks, and change in 9HPT-time from baseline to Week-120.ResultsCompared with placebo, ocrelizumab reduced the time-to 12- and 24-week-CP of ≥15% increase on 9HPT by 37% (hazard ratio [HR]=0.627; p=0.001) and 39% (HR=0.607; p=0.002) for both-hands, 30% (HR=0.699; p=0.011) and 40% (HR=0.599; pConclusionOcrelizumab treatment lowered the risk of progression of upper extremity disability, measured by 9HPT, compared with placebo in PPMS patients.