Communicating the relevance of neurodegeneration and brain atrophy to multiple sclerosis patients: patient, provider and researcher perspectives.

Central nervous system (CNS) atrophy provides valuable additional evidence of an ongoing neurodegeneration independent of lesion accrual in persons with multiple sclerosis (PwMS). However, there are limitations for interpretation of CNS volume changes at individual patient-level. Patients are receiving information on the topic of atrophy through various sources, including media, patient support groups and conferences, and discussions with their providers.

COVID-19 Vaccination in Multiple Sclerosis and Inflammatory Diseases: Effects from Disease-Modifying Therapy, Long-Term Seroprevalence and Breakthrough Infections.

Background: To determine the effect of disease-modifying therapies (DMT) on humoral postvaccine seroconversion, long-term humoral response, and breakthrough COVID-19 infections in persons with multiple sclerosis (PwMS) and other neuroinflammatory disorders. Methods: A total of 757 PwMS and other neuroinflammatory disorders were recruited in two MS centers and vaccinated with one of the FDA-approved vaccines (BNT162b2, mRNA-1273, Ad26.COV2.

A prospective study to validate the expanded timed get-up-and-go in a population with multiple sclerosis.

Background: Timed 25-foot walk (T25FW) test serves as gold standard in care of persons with multiple sclerosis (PwMS) and as walking measure of regulatory trials.

Objective: To validate and determine the clinical utility of Expanded Timed Get-Up and Go (ETGUG) as a disability measure in MS.

Methods: ETGUG intra-rater and inter-rater reproducibility was determined in 65 PwMS that were examined twice in two centres over 1-week.

Elevated spermidine serum levels in mild cognitive impairment, a potential biomarker of progression to Alzheimer dementia, a pilot study.

Background/aims: There is a close link between iron and polyamine biosynthesis and metabolism. In a recent study, we reported alterations in the serum levels of hepcidin and other iron-related proteins in Alzheimer's disease (AD) patients (Sternberg et al., 2017).

Leptomeningeal, dura mater and meningeal vessel wall enhancements in multiple sclerosis.

Background: Leptomeningeal contrast enhancement (LMCE) has previously shown potential to be an indirect marker for leptomeningeal inflammation in multiple sclerosis (MS). Dura mater (DME), inclusive falx cerebri (FCE) enhancement and meningeal vessel wall enhancement (VWE) represent two other meningeal enhancement patterns in MS that have not been extensively studied.

Objectives: To investigate the frequency of LMCE, DME/FCE and VWE in patients with MS and their associations with demographic, clinical and MRI characteristics in a longitudinal retrospective study.

Late onset multiple sclerosis is associated with more severe ventricle expansion.

Background: Late-onset multiple sclerosis (LOMS) is associated with faster disability progression than persons with adult-onset MS (PwAOMS). The differences in brain atrophy are currently unknown.

Objectives: To determine MRI-derived atrophy rates in persons with late-onset MS (PwLOMS) and compare them to an age-matched and disease duration-matched sample of PwAOMS.

Sex-Specific Differences in Life Span Brain Volumes in Multiple Sclerosis.

Background And Purpose: Numerous sex-specific differences in multiple sclerosis (MS) susceptibility, disease manifestation, disability progression, inflammation, and neurodegeneration have been previously reported. Previous magnetic resonance imaging (MRI) studies have shown structural differences between female and male MS brain volumes. To determine sex-specific global and tissue-specific brain volume throughout the MS life span in a real-world large MRI database.

Functional Connectivity and Structural Disruption in the Default-Mode Network Predicts Cognitive Rehabilitation Outcomes in Multiple Sclerosis.

Background And Purpose: Efficacy of restorative cognitive rehabilitation can be predicted from baseline patient factors. In addition, patient profiles of functional connectivity are associated with cognitive reserve and moderate the structure-cognition relationship in people with multiple sclerosis (PwMS). Such interactions may help predict which PwMS will benefit most from cognitive rehabilitation.

Recovery of cognitive function after relapse in multiple sclerosis.

Background: Cognitive impairment is common in multiple sclerosis (MS) but its manifestation as acute disease activity is underappreciated.

Objective: The aim of this study is to examine recovery after MS relapse on multiple tests of cognitive and motor function and explore correlates of change with Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI), and cognitive reserve.

Methods: Fifty relapsing group (RG) and matched stable participants were examined at baseline, during relapse, and at 3-month follow-up.

Atrophied Brain T2 Lesion Volume at MRI Is Associated with Disability Progression and Conversion to Secondary Progressive Multiple Sclerosis.

Background Atrophied T2 lesion volume at MRI is an imaging measure that reflects the replacement of T2 lesions by cerebrospinal fluid spaces in patients with multiple sclerosis (MS). Purpose To investigate the association of atrophied T2 lesion volume and development of disability progression (DP) and conversion to secondary progressive MS (SPMS). Materials and Methods This retrospective study included 1612 participants recruited from 2006 to 2016 and followed up for 5 years with clinical and MRI examinations.

Teriflunomide's effect on humoral response to Epstein-Barr virus and development of cortical gray matter pathology in multiple sclerosis.

Background: Teriflunomide has been shown to slow cortical gray matter (GM) atrophy in patients with multiple sclerosis (MS). Previous work showed that higher levels of Epstein-Barr virus (EBV) are associated with greater development of cortical pathology in MS.

Objectives: To investigate whether the effect of teriflunomide on cortical volume loss in relapsing MS patients may be associated with the change in humoral response to EBV.

Cumulative gadodiamide administration leads to brain gadolinium deposition in early MS.

Objective: Frequent administration of gadolinium-based contrast agents in multiple sclerosis (MS) may increase signal intensity (SI) unenhanced T1-weighted imaging MRI throughout the brain. We evaluated the association between lifetime cumulative doses of gadodiamide administration and increased SI within the dentate nucleus (DN), globus pallidus (GP), and thalamus in patients with early MS.

Methods: A total of 203 patients with MS (107 with baseline and follow-up MRI assessments) and 262 age- and sex-matched controls were included in this retrospective, longitudinal, 3T MRI-reader-blinded study.

No association between variations in extracranial venous anatomy and clinical outcomes in multiple sclerosis patients over 5 years.

Background: No longitudinal, long-term, follow-up studies have explored the association between presence and severity of variations in extracranial venous anatomy, and clinical outcomes in patients with multiple sclerosis (MS).

Objective: This prospective 5-year follow-up study assessed the relationship of variations in extracranial venous anatomy, indicative of chronic cerebrospinal venous insufficiency (CCSVI) on Doppler sonography, according to the International Society for Neurovascular Disease (ISNVD) proposed consensus criteria, with clinical outcomes and disease progression in MS patients.

Methods: 90 MS patients (52 relapsing-remitting, RRMS and 38 secondary-progressive, SPMS) and 38 age- and sex-matched HIs were prospectively followed for 5.

Aging and Brain Atrophy in Multiple Sclerosis.

Background And Purpose: Brain atrophy accelerates at the age of 60 in healthy individuals (HI) and at disease onset in multiple sclerosis (MS) patients. Whether there is an exacerbating effect of aging superimposed on MS-related brain atrophy is unknown. We estimated the aging effect on lateral ventricular volume (LVV) and whole brain volume (WBV) changes in MS patients.

Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study.

Pathologic changes in cortical gray matter (GM) and leptomeninges contribute to disability worsening in patients with multiple sclerosis (MS), but there is little evidence whether disease-modifying treatments can slow down cortical pathology in MS. To investigate the effect of teriflunomide (TFM) and dimethyl fumarate (DMF) in reducing cortical pathology, as determined by percentage cortical volume change (PCVC) and leptomeningeal contrast enhancement (LMCE) on MRI. This was a retrospective, single-center, observational study that selected 60 TFM- and 60 DMF-treated MS patients over 24 months.

Dalfampridine benefits ambulation but not cognition in multiple sclerosis.

Background: Impaired cognition and ambulation are common in multiple sclerosis (MS). Dalfampridine is the first Food and Drug Administration (FDA)-approved medication to treat impaired ambulation in MS. Dalfampridine may benefit patients with cognitive impairment, given its effects on saltatory conduction and the association between cognitive and motor function.

Brain Iron at Quantitative MRI Is Associated with Disability in Multiple Sclerosis.

Purpose To study deep gray matter susceptibility in multiple sclerosis (MS) by using quantitative susceptibility mapping (QSM) and to assess the relationship between susceptibility and clinical disability. Materials and Methods For this prospective study between March 2009 and November 2013, 600 participants with MS (452 with relapsing-remitting MS and 148 with secondary progressive MS) and 250 age- and sex-matched healthy control participants were imaged with 3.0-T MRI to measure magnetic susceptibility.

Effect of switching from glatiramer acetate 20 mg/daily to glatiramer acetate 40 mg three times a week on gray and white matter pathology in subjects with relapsing multiple sclerosis: A longitudinal DTI study.

Background: Glatiramer acetate (GA) 40 mg × 3/weekly was approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). While the beneficial effect of GA 20 mg/daily in MS patients on non-conventional MRI measures has been demonstrated, the effect of GA 40 mg × 3/weekly at the microstructural tissue level has yet to be explored.

Objective: To investigate the effect of switching from GA 20 mg/daily to GA 40 mg × 3/weekly on the evolution of microstructural changes in the thalamus and normal appearing white matter (NAWM), using diffusion tensor imaging (DTI).

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.

Interferon β for Multiple Sclerosis.

Despite that the availability of new therapeutic options has expanded the multiple sclerosis (MS) disease-modifying therapy arsenal, interferon β (IFN-β) remains an important therapy option in the current decision-making process. This review will summarize the present knowledge of IFN-β mechanism of action, the overall safety, and the short- and long-term efficacy of its use in relapsing remitting MS and clinically isolated syndromes. Data on secondary progressive MS is also provided, although no clear benefit was identified.

Fingolimod anti-inflammatory and neuroprotective effects modulation of RAGE axis in multiple sclerosis patients.

Background: We investigated Fingolimod treatment effects on the RAGE (receptor for advanced glycation endproducts) axis in multiple sclerosis (MS) patients. The primary outcome of the study was whether Fingolimod treatment increases serum levels of the soluble RAGE isoforms, sRAGE and esRAGE - both being considered putative endogenous inhibitors of RAGE signaling. Additional variables were serum levels of RAGE ligands, the high mobility group box (HMGB)1 and pentosidine.

Ocrelizumab: a B-cell depleting therapy for multiple sclerosis.

Multiple sclerosis (MS) is the most common neurological disease responsible for early disability in the young working population. In the last two decades, based on retrospective/prospective data, the use of disease-modifying therapies has been shown to slow the rate of disability progression and prolonged the time to conversion into secondary-progressive MS (SPMS). However, despite the availability of several approved therapies, disability progression cannot be halted significantly in all MS patients.