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Sajida Sabsabi,1 Elio Mikhael,2 Georges Jalkh,1 Gabrielle Macaron,1,3 Mary Rensel3 1Department of Neurology, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon; 2Department of Internal Medicine, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon; 3Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USACorrespondence: Mary Rensel, Email renselm@ccf.orgIntroduction: A number of disease-modifying therapies have been approved for use in relapsing-remitting multiple sclerosis (MS) in the past two decades. However, only few treatment options are available for patients with secondary progressive multiple sclerosis (SPMS). Siponimod has recently been approved for use in patients with active forms of SPMS (who experience clinical relapses or new lesions on MRI superimposed on secondary progression independent of relapse activity).Objective: The aim of this article is to provide a comprehensive review on the mechanism of action, efficacy, safety, cost effectiveness and patient adherence with siponimod.Methods: We performed a PubMed search using the search terms: “siponimod”, “secondary progressive multiple sclerosis”, “sphingosine 1-phosphate modulators”. Titles and abstract were screened and selected for relevance to the key section of this article.Findings: Siponimod is an oral sphingosine-1-phosphate receptor (S1PR) modulator with selectivity to S1PR-1 and 5. Modulation of this receptor on lymphocytes causes its internalization and degradation, preventing their egress from lymphoid tissues to the blood. In the pivotal Phase 3 randomized controlled trial EXPAND, siponimod was superior to placebo in reducing the risk of disability progression confirmed at 3 and 6 months, as well as the development of new MRI lesions and the rate of brain volume loss. Secondary analysis also showed a benefit on measures of cognitive functioning. The risk of lymphopenia and first-dose bradycardia appears to be lower with siponimod compared to non-selective S1P1R modulators. Different CYP2C9 genotypes affect the metabolism of siponimod; hence, genetic testing is required to adapt the titration and final dose accordingly.Conclusion: Long-term extension and real-world studies will allow further evaluation of efficacy and safety in this population. Future research should focus on better defining SPMS, and identifying biomarkers of progression and outcome measures of treatment response in this category of patients.Keywords: secondary progressive multiple sclerosis, siponimod, efficacy, safety

Background: Effective communication between providers and people with multiple sclerosis (pwMS) is essential., Objectives: To determine the level of concordance between provider- and pwMS-reported disease course., Methods: Patient encounters from December 2015 through April 2020 were retrospectively reviewed for MS disease course self-reported by the patient and separately documented by the provider at each visit. The proportion of agreement was compared across disease course Cohen's kappa, and subsequently stratified by sex, race, and level education., Results: Across 1335 encounters, the proportion of disease course agreement varied. Compared with RRMS, there was statistically significant difference across all other disease courses. Overall concordance between providers and pwMS was 64 % with a Cohen's kappa of 0.312. Concordance was higher amongst female patients, black patients, and patients with a higher level of education (>14 years)., Conclusion: Overall agreement on MS disease course amongst patients and providers was suboptimal. A concerted effort to understand these discrepancies is needed., Competing Interests: Declaration of competing interest Dr. Aboseif has no disclosures. Dr. Amin received a Novartis fellowship award (NGC44741). Dr. Macaron has served on advisory boards for Biologix, Genentech-Roche, Merck, and Novartis; received speaker fees from Biologix, Merck, and Novartis; and participated in educational activities for Neurology Live and John Hopkins's e-Literature Review. Dr. Ontaneda receives research support from Genentech, Genzyme, National Institutes of Health, National Multiple Sclerosis Society, Novartis Patient Centered Outcomes Research Institute, and Race to Erase MS Foundation. He has received consulting fees from Biogen Idec, Genentech/Roche, Genzyme, Janssen, Merck, and Novartis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: We report a challenging case of autoimmune encephalitis in a patient with a thymoma harboring titin and acetylcholine receptor antibodies, who experienced multiple relapses despite thymectomy and aggressive first-line immunotherapy, and for whom GABA A receptor antibodies were ultimately identified., Case Presentation: This 40-year-old man presented with headaches, weakness, diplopia, hearing loss, and seizures progressing to status epilepticus. Brain MRI showed multifocal cortical and subcortical T2/fluid attenuated inversion recovery hyperintense lesions without enhancement. Initial neural antibody testing identified only acetylcholine receptor and titin antibodies. He presented multiple severe relapses despite complete thymoma resection, intravenous methylprednisolone with immunoglobulins or plasmapheresis, and mycophenolate mofetil. Second-line immunotherapy with rituximab was successful to alleviate symptoms and normalize the EEG and MRI after identification of anti-GABA A receptor antibodies on more comprehensive neural antibody testing for autoimmune encephalitis., Conclusion: This case demonstrates the complexity and importance of identifying pathogenic antibodies and selecting 2nd line treatment accordingly in patients with autoimmune encephalitis when multiple antibodies coexist. Despite tumor resection, aggressive immunotherapy may be needed to prevent further deterioration in anti-GABA A receptor encephalitis., Competing Interests: M.B., C.R., A.K., H.C., L.L.-G., G.M., and C.L. report no conflict of interest in relation to this work. A.B. reports that he holds the London Health Sciences Centre and London Health Sciences Foundation Chair in Neural Antibody Testing for Neuro-Inflammatory Diseases, and receives support from the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario (AMOSO)., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Cognitive impairment (CI) is common in multiple sclerosis (MS). Processing speed (PS) is often affected, making it an ideal target for monitoring CI. This study aims to evaluate the association between disease-modifying therapy (DMT) use and intensity and longitudinal changes in Processing Speed Test (PST) scores for individuals with MS., Methods: A retrospective analysis of individual PST scores at a single MS center was conducted. Individuals with 2 or more PST assessments were included. Scores on the PST were compared longitudinally between those who had been on a DMT for 2 or more years and those who had been off a DMT for 2 or more years and between those on high-efficacy DMTs and those on low-/moderate-efficacy DMTs. A linear regression model was approximated to evaluate the rate of cognitive change over time. A propensity score adjustment was conducted using a multivariable logistic regression., Results: The cohort was 642 individuals, 539 on DMT and 103 off DMT. Median age and disease duration was 49.7 (IQR 42.4-57.9) and 16.6 years (IQR 9.3-23.0) in the DMT group, and 58.9 (IQR 52.2-65.3) and 20.0 years (IQR 14.1-31.4) in the non-DMT group. Both cohorts were predominantly female (75% DMT, 79.6% non-DMT), with a mean of 4 assessments (IQR 3-5), and an average monitoring duration of 1.9 years (1.2-2.4) in the DMT group, and 1.8 years (1.4-2.4) in the non-DMT group. After adjusting for multiple factors, DMT status and intensity were not found to be significant predictors of longitudinal PST change., Conclusions: Neither DMT status nor intensity was a significant predictor of cognitive processing speed over a period of approximately 2 years. Future prospective studies are needed to further support these findings., Competing Interests: FINANCIAL DISCLOSURES: Dr Amin received a Novartis fellowship award (NGC44741). Dr Macaron has served on advisory boards for Biologix, Genentech-Roche, Merck, and Novartis; received speaker fees from Biologix, Merck, and Novartis; and participated in educational activities for NeurologyLive® and John Hopkins's e-Literature Review. Dr Ontaneda receives research support from Genentech, Genzyme, National Institutes of Health, National Multiple Sclerosis Society, Novartis Patient Centered Outcomes Research Institute, and Race to Erase MS Foundation. He has received consulting fees from Biogen Idec, Genentech/Roche, Genzyme, Janssen, Merck, and Novartis. The other authors have no conflicts of interest., (© 2024 Consortium of Multiple Sclerosis Centers.)

With a rapidly aging global population and improvement of outcomes with newer multiple sclerosis (MS)-specific disease-modifying therapies (DMTs), the epidemiology of MS has shifted to an older than previously described population, with a peak prevalence of the disease seen in the 55-65 years age group. Changes in the pathophysiology of MS appear to be age-dependent. Several studies have identified a consistent phase of disability worsening around the fifth decade of life. The latter appears to be independent of prior disease duration and inflammatory activity and concomitant to pathological changes from acute focal active demyelination to chronic smoldering plaques, slow-expanding lesions, and compartmentalized inflammation within the central nervous system (CNS). On the other hand, decreased CNS tissue reserve and poorer remyelinating capacity with aging lead to loss of relapse recovery potential. Aging with MS may imply longer exposure to DMTs, although treatment efficacy in patients >55 years has not been evaluated in pivotal randomized controlled trials and appears to decrease with age. Older individuals are more prone to adverse effects of DMTs, an important aspect of treatment individualization. Aging with MS also implies a higher global burden of comorbid illnesses that contribute to overall impairments and represent a crucial confounder in interpreting clinical worsening. Discontinuation of DMTs after age 55, when no evidence of clinical or radiological activity is detected, is currently under the spotlight. In this review, we will discuss the impact of aging on MS pathobiology, the effect of comorbidities and other confounders on clinical worsening, and focus on current therapeutic considerations in this age group., Competing Interests: GM has served on advisory boards for Genentech-Roche, Novartis, Mercks, and Biologix, received speaker fees from Biologix, Mercks, and Novartis, and participated in educational activities for Neurology Live and John Hopkin’s e-Litterature Review. CL has served on scientific advisory boards and/or as speaker for EMD-Serono, Biogen, Bristol-Myers Squibb, Roche, Novartis, Actelion, FindTx and Sanofi-Genzyme and has received a Grant for Multiple Sclerosis Innovation from Merck/EMD-Serono. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Macaron, Larochelle, Arbour, Galmard, Girard, Prat and Duquette.)

Introduction: Adult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, a strong collaborative multidisciplinary network is beneficial for shortening the diagnostic odyssey of these patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) are multidisciplinary international online meetings attended by more than 30 physicians and scientists from 15 participating sites that gather every month to discuss patients with atypical white matter disorders. We aim to present the experience of the WM Rounds Network and demonstrate the value of collaborative multidisciplinary international case discussion meetings in differentiating and preventing misdiagnoses between genetic white matter diseases and atypical MS., Methods: We retrospectively reviewed the demographic, clinical and radiological data of all the subjects presented at the WM Rounds since their creation in 2013., Results: Seventy-four patients (mean age 44.3) have been referred and discussed at the WM Rounds since 2013. Twenty-five (33.8%) of these patients were referred by an MS specialist for having an atypical presentation of MS, while in most of the remaining cases, the referring physician was a geneticist (23; 31.1%). Based on the WM Rounds recommendations, a definite diagnosis was made in 36/69 (52.2%) patients for which information was available for retrospective review. Of these diagnosed patients, 20 (55.6%) had a genetic disease, 8 (22.2%) had MS, 3 (8.3%) had both MS and a genetic disorder and 5 (13.9%) had other non-genetic conditions. Interestingly, among the patients initially referred by an MS specialist, 7/25 were definitively diagnosed with MS, 5/25 had a genetic condition (e.g., X-linked adrenoleukodystrophy and hereditary small vessel diseases like Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and COL4A1 -related disorder), and one had both MS and a genetic demyelinating neuropathy. Thanks to the WM Rounds collaborative efforts, the subjects who currently remain without a definite diagnosis, despite extensive investigations performed in the clinical setting, have been recruited in research studies aimed at identifying novel forms of genetic MS mimickers., Conclusions: The experience of the WM Rounds Network demonstrates the benefit of collective discussions on complex cases to increase the diagnostic rate and decrease misdiagnosis in patients with rare or atypical white matter diseases. Networks of this nature allow physicians and scientists to compare and share information on challenging cases from across the world, provide a basis for future multicenter research studies, and serve as model for other rare diseases., (Copyright © 2022 Huang, Giacomini, Massie, Venkateswaran, Trudelle, Fadda, Sharifian-Dorche, Boudjani, Poliquin-Lasnier, Airas, Saveriano, Ziller, Miller, Martinez-Rios, Wilson, Davila, Rush, Longbrake, Longoni, Macaron, Bernard, Tampieri, Antel, Brais and La Piana.)

Background: Severe residual visual loss (SRVL) is frequent in neuromyelitis optica spectrum disorders (NMOSD). Identifying higher-risk patients at onset is important to prevent disability accumulation., Objective: To determine predictors of SRVL in a large NMOSD cohort., Methods: Patient characteristics at last visual acuity (VA) evaluation were retrospectively collected. VA was scored 0: better than 20/40, 1: 20/40-20/99, 2: 20/100-20/200, and 3: worse than 20/200. SRVL was defined as a combined score (VA worst + best eye) ⩾ 4. Descriptive statistics were used to compare groups and logistic regression to evaluate predictors of VA., Results: 106 patients (mean age at disease onset (AO): 35.8 ± 16.5 years) were included. Patients with SRVL had earlier AO (mean: 26.7 vs 38.0 years) compared to non-SRVL group ( p = 0.005). Patients with AO < 21 years were more likely to have SRVL, be blind, present with binocular optic neuritis, have recurrent optic neuritis, and receive oral therapy first-line than those with AO ⩾ 21. After adjusting for race, sex, and disease duration, the odds of SRVL were 4.68 times higher in patients < 21 at disease onset (95% CI: 1.53-14.34, p = 0.007)., Conclusion: Early AO predicts SRVL in NMOSD, independent of disease duration. High-efficacy therapies should be considered for first-line treatment in this group.

Background: Annual screening for processing speed impairment (PSI) is recommended for patients with multiple sclerosis (pwMS). However, cognitive deficits in pwMS are heterogeneous, and whether PSI screening identifies patients with impairment in other cognitive domains is unclear. The objective of this study was to examine sensitivity and specificity of the self-administered, computerized Processing Speed Test (PST) in identifying cognitive impairment defined by a comprehensive neuropsychological battery (NPT)., Methods: Ninety-one pwMS completed PST and NPT, with raw scores demographically adjusted. Cognitive impairment on NPT was defined as performance <5 th percentile in at least one domain. Receiver operating characteristic (ROC) analyses were performed to determine the ability of the PST to discriminate between cognitively normal (CN) and cognitively impaired with PSI (CI-PSI) and cognitively impaired with normal processing speed (CI-PSN) groups., Results: Cognitive impairment was observed in 23.1% of pwMS on PST and in 42.9% on NPT. PST demonstrated excellent ability to discriminate between CN (57.1%) and CI-PSI (20.9%) groups (Area Under the Curve [AUC] = 0.86, p < 0.001). In contrast, PST was unable to discriminate CN and CI-PSN (22.0%) groups (AUC = 0.42, p = 0.32)., Conclusion: The PST demonstrates excellent ability to detect PSI in pwMS but is unable to identify cognitively impaired pwMS without PSI, highlighting the importance of developing additional screening measures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab), and are associated with better control of disease activity and long-term outcomes in patients with MS compared to older injectable therapies (interferon beta and glatiramer acetate). However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach.

Background: Comprehensive 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., Method: We 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., Results: A 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., Conclusions: Integration of technology-enabled data capture in routine clinical practice allows acquisition of comprehensive standardized data for use in patient care and clinical research., (© 2019 American Academy of Neurology.)

Knowledge on the clinical and radiological phenotype of myelin oligodendrocyte glycoprotein (MOG)-related disorders has been growing. We report the case of a patient who presented with subacute onset myelitis after an upper respiratory tract infection with normal cord imaging at onset and follow-up after 4 months (absence of lesions and atrophy), high-titer positive MOG-IgG, and a broad workup excluding other etiologies. The full clinical and radiological spectrum of MOG-related disorders is yet to be completely understood. Testing for MOG-IgG using cell-based assays should be considered in imaging-negative myelitis particularly if initial testing is non-revealing.

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 R 2 =0.46). For CST, significant variables included age and NQ-LE (adjusted R 2  = 0.30). For MDT, significant variables included PDDS, PROMIS-10 physical, NQ-UE, NQ-LE, T2LV, and WBF (adjusted R 2 =0.37). For WST, significant variables included sex, PDDS, NQ-LE, T2LV, and CA (adjusted R 2 =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., Competing Interests: Declaration of Competing Interest Dr. Laura Baldassari has received personal fees for serving on a scientific advisory board for Teva. Dr. Kunio Nakamura has received personal fees for consulting from NeuroRx Research, speaking from Sanofi Genzyme, and license from Biogen Idec. He has received research support from NIH NINDS, NMSS, DOD, Biogen, Sanofi Genzyme, and Novartis. Dr. Brandon Moss reports personal compensation for consulting for Genentech and speaking for Genzyme. Dr. Gabrielle Macaron has served on an advisory board for Genentech. She receives fellowship funding from Biogen (#6873-P-FEL). Ms. Hong Li: No declarations of interest. Ms. Malory Weber: No declarations of interest. Dr. Stephen Jones has received travel and speaking fees from Siemens and IMRIS, speaking fees from Radnet and Saint Judes, research support and travel fees from MS PATHS, and research support from the NIH. Dr. Stephen Rao has received honoraria, royalties or consulting fees from Biogen, Genzyme, Novartis, American Psychological Association, International Neuropsychological Society and research funding from the National Institutes of Health, US Department of Defense, National Multiple Sclerosis Society, CHDI Foundation, Biogen, and Novartis. He contributed to intellectual property that is a part of the MSPT, for which he has the potential to receive royalties. Dr. Deborah Miller has contributed to intellectual property that is a part of the MSPT, for which she has the potential to receive royalties. Dr. Devon Conway has received research support paid to his institution from the National Multiple Sclerosis Society and Novartis Pharmaceuticals. He has received personal consulting fees from Novartis Pharmaceuticals and Tanabe Laboratories. Dr. Robert Bermel has served as a consultant for Biogen, Genzyme/Sanofi, Genentech/Roche, and Novartis. He receives research support from Biogen and Genentech, and contributed to intellectual property that is a part of the MSPT, for which he has the potential to receive royalties. Dr. Jeffrey Cohen has received personal fees for consulting for Convelo, Population Council; speaking for Mylan; and serving as an Editor of Multiple Sclerosis Journal. Dr. Daniel Ontaneda has received research support from National Multiple Sclerosis Society, National Institutes of Health, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, and Genzyme. He has also received consulting fees from Biogen, Genentech/Roche, Genzyme, Novartis, and Merck. Dr. Marisa McGinley has served on scientific advisory boards for Genzyme and Genentech., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose of Review: With the recognition that pediatric-onset multiple sclerosis (POMS) is characterized by more prominent disease activity, earlier age at onset of disability milestones, and more prominent cognitive impairment compared with physical disability earlier in the disease course compared with adult-onset multiple sclerosis (AOMS), there has been increasing interest in identifying optimal and safe treatment approaches to achieve better disease control in this group. Injectable therapies have been traditionally used as first line in this population, although not formally approved. This review focuses on current treatment and monitoring approaches in POMS., Recent Findings: In the past few years, and despite the paucity of FDA-approved medications for use in POMS, an increasing trend toward using newer disease-modifying therapies (DMTs) in this group is observed. However, escalation (as opposed to induction) remains the most frequent approach, and many children continue to be untreated before age 18, particularly before age 12. The only FDA- and EMA-approved disease-modifying therapy in POMS is fingolimod; however, dimethyl fumarate, teriflunomide, natalizumab, ocrelizumab, and alemtuzumab either have been evaluated in observational studies or are being currently investigated in formal randomized controlled trials for use in POMS and appear to be safe in this group. Autologous hematopoietic stem cell transplantation has also been evaluated in a small series. Clinical outcome measures and MS biomarkers have been poorly studied in POMS; however, the use of composite functional scores, neurofilament light chain, optical coherence tomography, and imaging findings is being increasingly investigated to improve early diagnosis and efficient monitoring of POMS. Off-label use of newer DMTs in POMS is increasing, and based on retrospective data, and phase 2 trials, this approach appears to be safe in children. Results from ongoing trials will help clarify the safety and efficacy of these therapies in the future. Fingolimod is the only FDA-approved medication for use in POMS. Outcome measures and biomarkers used in AOMS are being studied in POMS and are greatly needed to quantify treatment response in this group.

Background: Tuberculosis screening is recommended in multiple sclerosis patients starting certain disease-modifying therapies. Disease-modifying therapies may affect interferon-gamma release assay results., Objective: To determine the effects of multiple sclerosis disease-modifying therapies on interferon-gamma release assay results., Methods: Indeterminate interferon-gamma release assay results among multiple sclerosis patients were compared across disease-modifying therapies by Fisher's exact test. Logistic regression evaluated the effects of lymphopenia on interferon-gamma release assay results., Results: A total of 1058 patients underwent interferon-gamma release assay: 2.0% (21) positive, 6.1% (65) indeterminate, with 59.4% (628) on disease-modifying therapies. Results were significantly different across disease-modifying therapies ( P  = 0.002). Absolute lymphocyte count less than 0.5 k/μL had 9.39 times (95% confidence interval 5.2-17.0) increased odds of indeterminate interferon-gamma release assay results., Conclusions: Disease-modifying therapies affecting lymphocytes had a higher risk of indeterminate interferon-gamma release assay results., (© The Author(s) 2019.)

Background: Spasticity can be associated with several hyperkinetic involuntary movements generally referred to as "spasms" despite different phenomenology and clinical characteristics., Objective: To better characterize the phenomenology and clinical characteristics of spasticity-associated involuntary movements., Methods: We performed a cross-sectional study of a consecutive patient sample from the spasticity clinic. Each patient was interviewed by a movement-disorder neurologist who conducted a standardized movement-disorder survey and a focused exam. Patients with involuntary movements were video-recorded and videos were independently rated by a separate blinded movement-disorder neurologist., Results: Sixty-one patients were included (54% female, mean age 49.7 ± 13.9 years). Of the entire cohort, 11.5% had spinal, 44.3% had cerebral, and 44.3% had mixed-origin spasticity. Fifty-eight patients (95%) reported one or more involuntary movements: 75% tonic spasms (63% extensor, 58% isometric, 41% flexor/adductor), 52% spontaneous clonus, 34% myoclonus, 33% focal dystonia, and 28% action tremor. One third of the involuntary movements were painful. Only 53% of patients reported that their involuntary movements were much or very-much improved with their current anti-spasticity management. Patients treated with intrathecal baclofen therapy were more likely to report much or very-much improvement compared to patients receiving oral and/or botulinum therapy (P = 0.0061 and 0.0069 respectively)., Conclusion: Most spastic patients experience spasticity-associated involuntary movements of variable phenomenology and impact. However, only half of these patients experience significant improvement with the current management strategies. More research is needed to explore better treatment options for spasticity-associated involuntary movements with focus on phenomenology-specific approaches., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Multiple sclerosis is a chronic autoimmune disease of the central nervous system that results in varying degrees of disability. Progressive multiple sclerosis, characterized by a steady increase in neurological disability independently of relapses, can occur from onset (primary progressive) or after a relapsing-remitting course (secondary progressive). As opposed to active inflammation seen in the relapsing-remitting phases of the disease, the gradual worsening of disability in progressive multiple sclerosis results from complex immune mechanisms and neurodegeneration. A few anti-inflammatory disease-modifying therapies with a modest but significant effect on measures of disease progression have been approved for the treatment of progressive multiple sclerosis. The treatment effect of anti-inflammatory agents is particularly observed in the subgroup of patients with younger age and evidence of disease activity. For this reason, a significant effort is underway to develop molecules with the potential to induce myelin repair or halt the degenerative process. Appropriate trial methodology and the development of clinically meaningful disability outcome measures along with imaging and biological biomarkers of progression have a significant impact on the ability to measure the efficacy of potential medications that may reverse disease progression. In this issue, we will review current evidence on the physiopathology, diagnosis, measurement of disability, and treatment of progressive multiple sclerosis.

Morvan syndrome (MoS) is a rare paraneoplastic autoimmune disorder characterized by peripheral nerve hyperexcitability, autonomic dysfunction, and sleep disorders. Systemic lupus erythmatosus (SLE) cooccurs in 6-10% of patients with thymoma. It may occur before, concurrently with, or after thymoma diagnosis. This paper reports the first case of cooccurrence of SLE, thymic carcinoma, and MoS. The cooccurrence of SLE, thymoma, and MoS delineates the generalized autoimmunity process. Symptoms of both MoS and SLE abated upon tumor resection.

Anxiety, depression and suicidal thoughts are highly prevalent comorbidities of end-stage-renal-disease (ESRD). There are no studies in Lebanon on the prevalence of these symptoms in Lebanese end-stage-renal-disease patients. Moreover, the association between ESRD on one hand, and anxiety, depression and suicidal ideation on the other has never been established in Lebanon. Groups of patients at a high-risk of development of these symptoms are not determined. The Hospital Anxiety and Depression Score and M.I.N.I (module C) were used to measure the prevalence of anxiety, depression and suicidal ideation in 51 patients from the dialysis center of Hotel-Dieu de France Hospital in Lebanon. In our sample, 45% of included patients suffered from symptoms of anxiety and 50% presented symptoms of depression.The prevalence of suicidal ideation as detected by the M.I.N.I. is at 37%. No patients presented with a high risk of suicide. There was a statistically significant correlation between the existence of organic comorbidities and the presence of symptoms of depression and suicidal ideation. As for anxiety, the association was marginally significant. The results obtained by our study are consistent with those found in studies performed in other societies. The profile of depression- and suicidal ideation-prone patients has been determined. It consists of patients with at least one medical comorbidity to the ESRD. This, in turn, should lead to increased awareness and better treatment of these psychiatric ailments, considering their impact on morbidity and mortality in ESRD.