Search

The clinical correlation of gadolinium-based contrast agents (GBCAs) has not been well studied in multiple sclerosis (MS). We investigated the extent to which the number of GBCA administrations relates to self-reported disability and performance measures.A cohort of MS patients was analyzed in this retrospective observational study. The main outcome was the association between the cumulative number of GBCA exposures (linear or macrocyclic GBCA), Patient-Determined Disease Steps (PDDS), and measures of physical and cognitive performance (walking speed test, manual dexterity test [MDT], and processing speed test [PST]). The analysis was performed first cross-sectionally and then longitudinally.The cross-sectional data included 1059 MS patients with a mean age of 44.0 years (standard deviation = 11.2). While the contrast ratio in globus pallidus weakly correlated with PDDS, MDT, and PST in a univariate correlational analysis (coefficients, 95% confidence interval [CI] = 0.11 [0.04, 0.18], 0.15 [0.08, 0.21], and -0.16 [-0.10, -0.23], respectively), the associations disappeared after covariate adjustment. A significant association was found between number of linear GBCA administrations and PDDS (coefficient [CI] = -0.131 [-0.196, -0.067]), and MDT associated with macrocyclic GBCA administrations (-0.385 [-0.616, -0.154]), but their signs indicated better outcomes in patients with greater GBCA exposures. The longitudinal data showed no significant detrimental effect of macrocyclic GBCA exposures.No detrimental effects were observed between GBCA exposure and self-reported disability and standardized objective measures of physical and cognitive performance. While several weak associations were found, they indicated benefit on these measures.

The sphingosine 1-phosphate (S1P) signalling pathways have important and diverse functions. S1P receptors (S1PRs) have been proposed as a therapeutic target for various diseases due to their involvement in regulation of lymphocyte trafficking, brain and cardiac function, vascular permeability, and vascular and bronchial tone. S1PR modulators were first developed to prevent rejection by the immune system following renal transplantation, but the only currently approved indication is multiple sclerosis. The primary mechanism of action of S1PR modulators in multiple sclerosis is through binding S1PR subtype 1 on lymphocytes resulting in internalisation of the receptor and loss of responsiveness to the S1P gradient that drives lymphocyte egress from lymph nodes. The reduction in circulating lymphocytes presumably limits inflammatory cell migration into the CNS. Four S1PR modulators (fingolimod, siponimod, ozanimod, and ponesimod) have regulatory approval for multiple sclerosis. Preclinical evidence and ongoing and completed clinical trials support development of S1PR modulators for other therapeutic indications.

Introduction. To overcome travel restrictions during the COVID-19 pandemic, consumer-based technology was rapidly deployed to the smartphones of individuals with Parkinson’s disease (PD) participating in a 12-month exercise trial. The aim of the project was to determine the feasibility of utilizing a combined synchronous and asynchronous self-administered smartphone application to characterize PD symptoms. Methods. A synchronous video virtual visit was completed for the administration of virtual Movement Disorder Society-Unified Parkinson’s Disease Rating Scale III (vMDS-UPDRS III). Participants asynchronously completed a mobile application consisting of a measure of upper extremity bradykinesia (Finger Tapping Test) and information processing. Results. Twenty-three individuals completed the assessments. The mean vMDS-UPDRS III was 23.65 ± 8.56 points. On average, the number of taps was significantly greater for the less affected limb, 97.96 ± 17.77 taps, compared to the more affected, 89.33 ± 18.66 taps (p = 0.025) with a significantly greater number of freezing episodes for the more affected limb ( p < 0.05 ). Correlation analyses indicated the number of errors and the number of freezing episodes were significantly related to clinical ratings of vMDS-UPDRS III bradykinesia (Rho = 0.44, p < 0.01 ; R = 0.43, p < 0.01 , resp.) and finger tapping performance (Rho = 0.31, p = 0.03 ; Rho = 0.32, p = 0.03 , resp.). Discussion. The objective characterization of bradykinesia, akinesia, and nonmotor function and their relationship with clinical disease metrics indicate smartphone technology provides a remote method of characterizing important aspects of PD performance. While theoretical and position papers have been published on the potential of telemedicine to aid in the management of PD, this report translates the theory into a viable reality.

Background and purpose The purpose was to determine the test-retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self-administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression-based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example. Methods Substudy 1 assessed test-retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples. Results The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician-administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample. Conclusions The self-administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting.

This case series describes 9 patients diagnosed with myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorder (MOGAD) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients developed neurological symptoms between 4 days and 5 weeks following SARS-CoV-2 infection. Myelitis was observed in 4 patients; 4 presented with optic neuritis; and encephalopathy was observed in 3. Serum MOG-IgG cell-based assay was medium or high positive in each case. The majority of patients had near-complete recovery following acute immunosuppression. This series adds to the growing number of cases of central nervous system demyelination following SARS-CoV-2 infection and highlights a potential role of infection in the immunopathogenesis of MOGAD.

Patient-reported outcome measures (PROMs) are often used in clinical research, but little is known about their performance as longitudinal outcomes.We used data from ASCEND, a large SPMS trial (PROM scores changed little over the 2 years of follow-up. In contrast to physical disability measures, there was no consistent trend in PROM change: significant worsening occurred about as often as improvement. Using a 6-month confirmation reduced the number of both worsening and improvement events without altering their relative balance. There was no clear difference in worsening events in groups based on population characteristics, nor was there a noticeable effect using different thresholds for clinically significant change.We found little consistent change in MSIS-29 and SF-36 over 2 years of follow-up in people with SPMS. Our findings show a disconnect between disability worsening and PROM change in this population. Our findings raise caution about the use of these PROMs as primary outcome measures in SPMS trials and call for a critical reappraisal of the longitudinal use of these measures in SPMS trials.

The coronavirus disease 2019 (COVID-19) pandemic has catalyzed the rapid adoption of telemedicine which encompasses synchronous and asynchronous interactions between patients and providers. In order to facilitate this rapid deployment, there has been numerous regulatory changes to ensure caregivers can effectively communicate with patients during this time. We illustrate a model where people, processes, and technology work together to address the comprehensive needs of multiple sclerosis (MS) patients. We provide a template for how multidisciplinary, academic practices can implement a rapid shift to virtual management during the pandemic using existing infrastructure that can be widely adopted to care for patients with chronic diseases. Telemedicine was incorporated into our entire practice, which encompasses neurology, rehabilitation, advanced practice providers, fellows, social work, and behavioral medicine. Our patient satisfaction results remained stable across almost all domains when compared to survey results from our typical, in-office visits. Our experience demonstrates telemedicine’s transformative potential in successfully managing a multidisciplinary MS clinic during the time of a pandemic and outlines a potential path for other practices to follow.

Background: Therapeutic research in multiple sclerosis (MS) has focused on the development of treatments with little investigation regarding the possibility of discontinuation of disease-modifying therapies (DMTs). Objective: To understand the opinion of individuals with MS concerning stopping DMTs and the factors that influence the decision-making process. Methods: A mixed method approach was used starting with three focus groups from which a survey was developed. This survey was sent to 1000 participants in the North American Research Committee on Multiple Sclerosis registry who met inclusion criteria (age ⩾45 years; on most recent DMT for ⩾5 years). Descriptive analysis and structural equation modeling were used. Results: Of 1000 participants receiving the survey, 377 provided complete responses and met inclusion criteria. Only 11.9% of participants reported that if their disease was considered stable, they would consider coming off medications. A high level of external locus of control in influential others such as physicians significantly decreased the likelihood of considering discontinuation. Conclusions: Most individuals with MS report being unlikely to consider stopping MS therapy if their disease was considered “non-active.” As the results of studies concerning DMT discontinuation are obtained, information from providers will be an important part of individuals’ decision-making process.

Importance Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS. Observations MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid–specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease. Conclusions and Relevance MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.

Background Teleneurology for multiple sclerosis (MS) care was considered feasible, but utilization was limited. Objective To describe how the existing teleneurology populations at two academic MS Centers changed during the COVID-19 pandemic. Methods In this cross-sectional study, we captured all in-person and teleneurology visits at two academic MS Centers between January 2019 and April 2020. We compared group differences between the Centers, and COVID-related changes using T-, chi-squared Kruskal-Wallis and Fisher exact tests. Results 2268 patients completed 2579 teleneurology visits (mean age 48.3 ± 13.3 years, 72.9% female). Pre-COVID, the Centers’ teleneurology populations were similar for age, sex, MS type, and disability level (all p > 0.1), but differed for race (96.5% vs 80.7% white, p ≤ 0.001), MS treatment (49.1% vs 32.1% infusible, p ≤ 0.001), and median distance from Center (72 vs 186 miles, p ≤ 0.001). Post-COVID, both Centers’ teleneurology populations had more black (12.7% vs 4.37%, p ≤ 0.001) and local (median 34.5 vs 102 miles, p ≤ 0.001) patients. Conclusion Teleneurology visits in 2019 reflected the organizational and local teleneurology reimbursement patterns of our Centers. Our post-COVID-19 changes illustrate the potential for payors and policy to change disparities in access to, or utilization of, remote care. Patients’ perception of care quality and value following this shift warrants study.

The diagnostic criteria for multiple sclerosis provide a comprehensive framework to facilitate accurate diagnosis. The criteria have evolved since the original description of the syndrome by Charcot in 1868 into a multidimensional scheme that incorporates clinical presentation, imaging, and paraclinical evidence to aid in the diagnostic process. Additionally, the criteria were initially intended for use in research studies but are now intended for both research and clinical use. The key features of the criteria now include aspects of the clinical presentation, establishing dissemination in time and space, role of MRI, and utility of CSF and other paraclinical tests. There still are aspects that need refinement, including incorporation of the anterior visual system, applicability in diverse populations and presentations, and development of unique biomarkers and advanced imaging techniques. The development of the diagnostic criteria will continue to be an iterative process based on ongoing research with an emphasis on creating a practical approach facilitating early and accurate diagnosis of MS.

Multiple sclerosis is a relatively common, immune-mediated neurologic disease of the central nervous system that can cause significant disability and lead to reduced quality of life. There are several currently approved disease-modifying therapies, and more in the pipeline being developed and tested. As the field learns more about the pathophysiology and natural course of the disease, the treatment approaches are also being investigated. This article reviews data on available treatments along with a discussion of future treatment targets under investigation.

Background: Teleneurology has been well described for acute stroke, but outpatient use has been limited. At home, virtual visits have the potential to improve access to neurological care. Introduction: This study reports on the use of a personal device videoconferencing platform for outpatient neurologic follow-up visits. Materials and Methods: This is a cross-sectional study that identified all virtual neurologic follow-up visits completed by patients ≥18 years at a single institution over 4 years. Virtual visits were conducted by personal smartphone or computer via videoconferencing with a provider. Patients were asked to rate their overall experience with the visit and provider (five-point scale). Travel distance from the institution was calculated using patient's home addresses. Results: Three thousand nine hundred thirteen patients completed 5,581 virtual visits during the study (mean age 49.4 ± 17.0 years, 58.7% female). Number of virtual visits increased from 30 in year 1 to 4,468 in year 4. Virtual visits were completed in all outpatient neurologic subspecialties. A total of 30.1% of patients were local (270 miles). A distance of 1,327,128 miles of travel was prevented across the 5,581 visits. On average, patients rated their overall virtual visit experience 4.7/5 ± 0.89 and rated their provider 4.9/5 ± 0.48. Discussion: Virtual visits prevented a substantial amount of travel and resulted in high patient satisfaction. The sizable proportion of local patients may indicate that teleneurology provides important access for reasons beyond travel distance. Conclusion: This study demonstrates the feasibility of implementing outpatient teleneurology services.

Background: The coronavirus disease of 2019 (COVID-19) pandemic and the need for social distancing have dramatically changed health care delivery. There is an urgent need to continue to deliver outpatient care for chronic neurological disease and teleneurology has the potential to fulfill this gap. Introduction: This study reports the implementation and utilization of teleneurology across all neurological subspecilities during the COVID-19 pandemic. Materials and Methods: This is a retrospective observational study that identified all in-person and teleneurology outpatient nonprocedural visits from January 5 to April 4, 2020, across neurological specialties at a single academic center. Visit volumes were assessed weekly and practice patterns were compared before and after March 15, 2020, as this was the date of a major statewide stay-at-home order in Ohio. Results: Before March 15 the mean in-person visit per week was 5129.4 and decreased to 866.7 after that date. The mean teleneurology visits per week increased from 209.1 to 2619.3 for the same time period. The overall teleneurology visit volume in the 3 weeks after March 15 increased by 533%. Discussion: In a relatively short time frame of 3 weeks, a single academic center was able to dramatically increase teleneurology visits to provide outpatient neurological care. Conclusions: This study demonostrates that teleneruology can be a solution for outpatient neurological care in the context of COVID-19. The increased utilization of teleneurology during this crisis has the potential to expand teleneurology and improve access to neurological care in the future outside the pandemic setting.

We describe the largest-to-date single-center implementation of tele-epilepsy. Beginning in 2017, all patients at a single tertiary care academic epilepsy center were offered the option to complete outpatient follow-up visits via video-conferencing using personal devices. A retrospective review of all patients who self-selected virtual visits over nearly 3 years showed 2140 patients completed 3698 tele-epilepsy visits, with 41% completing more than one visit during the study period. Based on the distance from the center to the home address, 26.7% of patients were local (≤50 miles), 30.5% were near regional (51-150 miles), 20.1% were far regional (151-270 miles), and 22.7% were remote (>270 miles), from 43 different states. An estimated 928 696 miles of travel was prevented, with a median travel distance saved of 124.5 miles (interquartile range = 45.0-253.0). The mean visit time was 15.7 (±10.4) minutes. More than 90% of patients gave the visit and provider experience the maximum rating, with a nearly 60% response rate on the post-visit survey. Virtual outpatient follow-up care provides a convenient way to connect with epilepsy specialists and reduce the burden of care by cutting travel time. Our experience demonstrates that outpatient tele-epilepsy is feasible, sustainable, and scalable.

Pediatric-onset multiple sclerosis (POMS) is rarer than adult-onset disease, and represents a different diagnostic and treatment challenge to clinicians. We review POMS clinical and radiographic presentations, and explore important differences between POMS and adult-onset MS natural histories and long-term outcomes. Despite having more active disease, current treatment guidelines for patients with POMS endorse the off-label use of lower-efficacy disease-modifying therapies (DMTs) as first line. We review the available MS DMTs, their evidence for use in POMS, and the contrasting treatment strategies of high-efficacy early treatment and escalation therapy. We introduce a new treatment approach, the "high-efficacy early treatment", or HEET strategy, based on using directly observed, high-efficacy intravenously infused DMTs as first-line therapies. Like other proposed POMS treatment strategies, HEET will need to be prospectively studied, and all treatment decisions should be determined by an experienced neurologist, the patient, and his/her parents.

BACKGROUND AND PURPOSE To analyze the relationship between cognitive processing speed, patient-reported outcome measures (PROMs), employment and magnetic resonance imaging (MRI) metrics in a large multiple sclerosis cohort. METHODS Cross-sectional clinical data, PROMs, employment and MRI studies within 90 days of completion of the Processing Speed Test (PST), a technology-enabled adaptation of the Symbol Digit Modalities Test, were collected. MRI was analyzed using semi-automated methods. Correlations of PST score with PROMs and MRI metrics were examined using Spearman's rho. Wilcoxon rank sum testing compared MRI metrics across PST score quartiles and linear regression models identified predictors of PST performance. Effects of employment and depression were also investigated. RESULTS In 721 patients (mean age 47.6 ± 11.4 years), PST scores were significantly correlated with all MRI metrics, including cord atrophy and deep gray matter volumes. Linear regression demonstrated self-reported physical disability, cognitive function, fatigue and social domains (adjusted R2 = 0.44, P

BackgroundComprehensive and efficient assessments are necessary for clinical care and research in chronic diseases. Our objective was to assess the implementation of a technology-enabled tool in MS practice.MethodWe analyzed prospectively collected longitudinal data from routine multiple sclerosis (MS) visits between September 2015 and May 2018. The MS Performance Test, comprising patient-reported outcome measures (PROMs) and neuroperformance tests (NPTs) self-administered using a tablet, was integrated into routine care. Descriptive statistics, Spearman correlations, and linear mixed-effect models were used to examine the implementation process and relationship between patient characteristics and completion of assessments.ResultsA total of 8022 follow-up visits from 4199 patients (median age 49.9 [40.2–58.8] years, 32.1% progressive course, and median disease duration 13.6 [5.9–22.3] years) were analyzed. By the end of integration, the tablet version of the Timed 25-Foot Walk was obtained in 89.0% of patients and the 9-Hole Peg Test in 94.8% compared with 74.2% and 64.3%, respectively before implementation. The greatest increase in data capture occurred in processing speed and low-contrast acuity assessments (0% prior vs 78.4% and 36.7%, respectively, following implementation). Four PROMs were administered in 41%–98% of patients compared with a single depression questionnaire with a previous capture rate of 70.6%. Completion rates and time required to complete each NPT improved with subsequent visits. Younger age and lower disability scores were associated with shorter completion time and higher completion rates.ConclusionsIntegration of technology-enabled data capture in routine clinical practice allows acquisition of comprehensive standardized data for use in patient care and clinical research.

Introduction La qualite de vie (HRQoL) des patients SEP est inferieure a la population generale. Optimiser le traitement suppose comprendre les variations de HRQoL apres initiation du traitement de fond. Objectifs Evaluer les variations notees dans Neuro-QoL apres initiation du traitement par natalizumab et comparer les variations des modules du Neuro-QoL sous natalizumab et ocrelizumab, une autre therapie hautement efficace. Patients et methodes Les T-scores des 12 modules Neuro-QoL etaient recueillis lors des visites de routine MS PATHS. Les scores Neuro-QoL des visites apres initiation du natalizumab ont ete compares avec les scores de base de Neuro-QoL pour calculer le taux annualise de variation et la probabilite de variation cliniquement significative (≥ 5 points). Des comparaisons etaient menees avec des patients traites par ocrelizumab apres ponderation et ajustement des scores de propension pour les co-traitements, l’annee et l’interaction medicament-annee. Resultats Les patients traites par natalizumab (n = 164) ont montre une amelioration significative sur 8/12 domaines. Les domaines avec une proportion de patients avec une amelioration de ≥ 5 points sont : troubles du sommeil, anxiete, perte de controle emotionnel et comportemental. Les taux d’amelioration annualises etaient superieurs sous natalizumab (n = 144) que sous ocrelizumab (n = 502) concernant les domaines : bien-etre (p = 0,02), troubles du sommeil (p = 0,003) et satisfaction a l’egard des roles et activites sociaux (p = 0,03). Discussion Le traitement par natalizumab a ete associe a des ameliorations significatives dans la plupart des domaines Neuro-QoL. Ces ameliorations etaient superieures chez les patients presentant un handicap initial, ce qui etaye la pertinence clinique de ces resultats. L’ampleur de ces ameliorations depassant celle d’un autre traitement efficace (ocrelizumab), il est peu probable qu’elles soient principalement dues a un biais d’anticipation. Conclusion Le natalizumab peut deboucher sur des ameliorations cliniquement significatives dans des aspects de la sante mentale et sociale telles qu’evaluees par Neuro-QoL.

Background Optimizing multiple sclerosis treatment warrants understanding of changes in physical, mental, and social health. Objective To assess the impact of natalizumab on Quality of Life in Neurological Disorders (Neuro-QoL) scores. Methods Annualized change in T-scores and likelihood of ≥5-point improvement over baseline were calculated for each Neuro-QoL domain after natalizumab initiation. Comparisons with ocrelizumab-treated patients were conducted after propensity score weighting and adjustment for relevant co-medications, year, and drug-year interaction. Results Among 164 natalizumab patients analyzed, 8 of 12 Neuro-QoL domains improved significantly, with greater improvement in patients with abnormal baseline Neuro-QoL. In the subgroup comparison of natalizumab-treated ( n = 145) and ocrelizumab-treated ( n = 520) patients, significant improvement occurred in 9 of 12 and 4 of 12 domains, respectively. The difference between groups was statistically significant for positive affect and well-being ( p = 0.02), sleep ( p = 0.003), and satisfaction with social roles and activities (SRA) ( p = 0.03) in the overall population and for emotional and behavioral dyscontrol ( p = 0.01), participation in SRA ( p = 0.0001), and satisfaction with SRA ( p = 0.02) in patients with abnormal baseline Neuro-QoL. Conclusions Natalizumab can produce clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias, as their magnitude exceeded improvements with another high-efficacy therapy, ocrelizumab.

Background Objective and longitudinal measurements of disability in patients with multiple sclerosis (MS) are desired in order to monitor disease status and response to disease-modifying and symptomatic therapies. Technology-enabled comprehensive assessment of MS patients, including neuroperformance tests (NPTs), patient-reported outcome measures (PROMs), and MRI, is incorporated into clinical care at our center. The relationships of each NPT with PROMs and MRI measures in a real-world setting are incompletely studied, particularly in larger datasets. Objectives To demonstrate the utility of comprehensive neurological assessment and determine the association between NPTs, PROMs, and quantitative MRI measures in a large MS clinical cohort. Methods NPTs (processing speed [PST], contrast sensitivity [CST], manual dexterity [MDT], and walking speed [WST]) and physical disability-related PROMs (Quality of Life in Neurological Disorders [Neuro-QoL], Patient Determined Disease Steps [PDDS], and Patient-Reported Outcomes Measurement Information System Global-10 [PROMIS-10] physical) were collected as part of routine clinical care. Fully-automated MRI analysis calculated T2-lesion volume (T2LV), whole brain fraction (WBF), thalamic volume (TV), and cervical spinal cord cross-sectional area (CA) for brain MRIs completed within 3 months of a clinic visit during which NPTs and PROMs were assessed. Spearman's rank correlation coefficients evaluated the cross-sectional associations of NPTs with PROMs and MRI measures. Linear regression was utilized to determine which combination of clinical characteristics, patient demographics, MRI measures, and PROMs best cross-sectionally explained each NPT result. Results 997 unique patients (age 47.7 ± 11.4 years, 71.8% female) who underwent assessments over a 2-year period were included. Correlations among NPTs and PROMs were moderate. PST correlations were strongest for Neuro-QoL upper extremity (NQ-UE) (Spearman's rho = 0.43) and lower extremity (NQ-LE) (0.47). CST correlations were strongest for NQ-UE (0.33), NQ-LE (0.36), and PDDS (-0.31). MDT correlations were strongest for NQ-UE (-0.53), NQ-LE (-0.54), and PDDS (0.53). WST correlations were strongest for PDDS (0.64) and NQ-LE (-0.65). NPTs also had moderate correlations with MRI metrics, the strongest of which were observed with PST (with T2LV (-0.44) and WBF (0.49)). Spearman's rho for other NPT-MRI correlations ranged from 0.23 to 0.36. Linear regression identified age, disease duration, PROMIS-10 physical, NQ-UE, NQ-LE, T2LV and WBF as significant cross-sectional explanatory variables for PST (adjusted R2=0.46). For CST, significant variables included age and NQ-LE (adjusted R2 = 0.30). For MDT, significant variables included PDDS, PROMIS-10 physical, NQ-UE, NQ-LE, T2LV, and WBF (adjusted R2=0.37). For WST, significant variables included sex, PDDS, NQ-LE, T2LV, and CA (adjusted R2=0.39). Conclusions Impaired performance on NPTs correlated with worse physical disability-related PROMs and MRI disease severity, but the strongest cross-sectional explanatory variables for each NPT component varied. This study supports the use of comprehensive, objective quantification of MS status in clinical and research settings. Future longitudinal analyses can determine predictors of treatment response and disability worsening.

• Alemtuzumab has been associated with stroke and cervicocephalic dissections. • Monitoring blood pressure is currently recommended by the EMA. • Monitoring blood pressure is not useful in predicting these rare side effects.

Introduction: Monoclonal antibodies are a potent therapeutic approach for relapsing-remitting multiple sclerosis. This group of medications comprises diverse mechanisms of action resulting in both shared and unique adverse effects.Areas covered: The major trials and safety profiles of natalizumab, alemtuzumab, daclizumab, rituximab, and ocrelizumab are discussed. While each drug has a unique safety profile, one of the potential safety concerns for all of these drugs is infection, including for some progressive multifocal leukoencephalopathy. Other potential side effects and required monitoring for each drug are addressed.Expert opinion: The treatment of multiple sclerosis is a balance between efficacy and safety. As a group, these medications are highly effective, but not without notable safety concerns; therefore more research is needed to understand the place these medications hold in the overall treatment algorithm.

A 12-year-old adolescent presented with refractory seizures and was found to have a mesial temporal lobe lesion. The patient underwent biopsy and was diagnosed with an arteriovenous malformation. Supratentorial lesions in the pediatric population can have a large variety of underlying etiologies, which can be challenging to differentiate on neuroimaging. In this report, we discuss the key features on MRI of several neoplastic, vascular, and infectious processes that can aide in the diagnosis.

Aging results in decreased neuromuscular function, which is likely associated with neurologic alterations. At present little is known regarding age-related changes in intracortical properties.In this study we used transcranial magnetic stimulation (TMS) to measure intracortical facilitation (ICF), short- and long-interval intracortical inhibition (SICI and LICI), motor evoked potential amplitude, and silent period duration in young and older adults (21.4+/-0.8years and 70.9+/-1.8years). These variables were assessed from the flexor carpi radialis muscle of the non-dominant arm under resting conditions, and during a submaximal contraction (intensity 15% maximum strength).Older adults exhibited increased SICI and LICI in comparison to young adults (SICI: 29.0+/-9.2% vs. 46.2+/-4.8% of unconditioned pulse; LICI: 6.5+/-1.7% vs. 15.8+/-3.3% of unconditioned pulse; P=0.04), and less ICF under resting conditions (74.6+/-8.7% vs. 104.9+/-6.9% of unconditioned pulse; P=0.02). These age-related differences disappeared during contraction, although the older adults did exhibit a longer silent period during contraction (112.5+/-6.5 vs. 84.0+/-3.9ms; P0.01).Collectively, these findings suggest increased GABA mediated intracortical inhibition with age.