Administrative data for observational research in multiple sclerosis: Opportunities and challenges

Ruth Ann Marrie, Kyla McKay

doi : 10.1177/13524585211055787

First Published November 17, 2021; pp. 3–6

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Progressive multifocal leukoencephalopathy in dimethyl fumarate-treated multiple sclerosis patients

Allison LM Jordan, Jennifer Yang, Caitlyn J Fisher, Michael K Racke, Yang Mao-Draayer

doi : 10.1177/1352458520949158

First Published August 18, 2020; pp. 7–15

Dimethyl fumarate (DMF), a fumaric acid with antioxidant and immunomodulatory properties, is among the most commonly used oral therapies for relapsing multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) has been associated with several disease-modifying therapies (DMTs), including DMF in treating MS. We present detailed clinical characteristics of nine PML cases and show that the PML incidence in DMF-treated patients is 0.02 per 1000 patients. In addition to persistent severe lymphopenia, older age appears to be a potential risk for PML. However, younger patients without lymphopenia were also observed to develop PML. DMF-associated PML has occurred in patients with absolute lymphocyte counts (ALCs) above the guideline threshold, suggesting that changes in specific subsets might be more important than total ALC. Furthermore, since DMF has been found to decrease immune cell migration by decreasing the expression of adhesive molecules, the cerebrospinal fluid (CSF) immune profile may also be useful for assessing PML risk in DMF-treated patients. This review provides an up-to-date assessment of PML cases occurring in DMF-treated patients and discusses other potential considerations in light of our current understanding of DMF’s mechanism of action on the immune system in the periphery and in the central nervous system (CNS).

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Charting a global research strategy for progressive MS—An international progressive MS Alliance proposal

Alan J Thompson, William Carroll, Olga Ciccarelli,Giancarlo Comi, Anne Cross, Alexis Donnelly, Anthony Feinstein, Robert J Fox, Anne Helme, Reinhard Hohlfeld, Robert Hyde, Pamela Kanellis, Douglas Landsman, Catherine Lubetzki, Ruth Ann Marrie, Julia Morahan, Xavier Montalban, Bruno Musch, Sarah Rawlings, Marco Salvetti, Finn Sellebjerg, Caroline Sincock, Kathryn E Smith, Jon Strum, Paola Zaratin, Timothy Coetzee

doi : 10.1177/13524585211059766

First Published December 1, 2021; pp. 16–28

Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term ‘active’ secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management.

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Current status of neuroprotective and neuroregenerative strategies in multiple sclerosis: A systematic review

Jessica R Allanachǂ, John W. Farrell, IIIǂ, Miceline Mésidorǂ,Soheila Karimi-Abdolrezaee

doi : 10.1177/13524585211008760

First Published April 19, 2021; pp. 29–48

Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in progressive MS, causing permanent axonal loss and irreversible disabilities. Strategies aimed at enhancing remyelination are critical to attenuate disease progression.

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Central vein sign and other radiographic features distinguishing myelin oligodendrocyte glycoprotein antibody disease from multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica

John R Ciotti, Noah S Eby, Matthew R Brier, Gregory F Wu, Salim Chahin, Anne H Cross, Robert T Naismith

doi : 10.1177/13524585211007086

First Published April 19, 2021; pp. 49–60

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) can radiographically mimic multiple sclerosis (MS) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Central vein sign (CVS) prevalence has not yet been well-established in MOGAD.

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Disability in multiple sclerosis is related to thalamic connectivity and cortical network atrophy

Menno M Schoonheim, Daniela Pinter, Stefanos E Prouskas, Tommy AA Broeders, Lukas Pirpamer, Michael Khalil, Stefan Ropele, Bernard MJ Uitdehaag, Frederik Barkhof, Christian Enzinger, Jeroen JG Geurts

doi : 10.1177/13524585211008743

First Published April 19, 2021; pp. 61–70

Thalamic atrophy is proposed to be a major predictor of disability progression in multiple sclerosis (MS), while thalamic function remains understudied.

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CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event

Manuel Comabella, Margareta A Clarke, Sabine Schaedelin, Mar Tintoré, Deborah Pareto, Nicolás Fissolo, Rucsanda Pinteac, Cristina Granziera, Jaume Sastre-Garriga, Pascal Benkert, Cristina Auger, Jens Kuhle, Xavier Montalban, Alex Rovira

doi : 10.1177/13524585211010082

First Published April 19, 2021; pp. 71–81

Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis.

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Effect of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea in multiple sclerosis: A randomized, double-blind, placebo-controlled trial (SAMS-PAP study)

Sulaiman Khadadah, R John Kimoff, Pierre Duquette, Vincent Jobin, Yves Lapierre, Andrea Benedetti, Fatema T Johara, Ann Robinson, Elaine Roger, Amit Bar-Or, Gabriel Leonard, Marta Kaminska, Daria A Trojan

doi : 10.1177/13524585211010390

First Published April 23, 2021; pp. 82–92

The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the Fatigue Severity Scale (FSS, preplanned primary outcome), another fatigue measure, sleep quality, somnolence, pain, disability, and quality of life in multiple sclerosis (MS) patients with obstructive sleep apnea-hypopnea (OSAH).

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Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy

Elisabetta Signoriello, Giacomo Lus, Simona Bonavita, Roberta Lanzillo, Francesco Saccà, Doriana Landi, Jessica Frau, Damiano Baroncini, Mauro Zaffaroni, Giorgia Teresa Maniscalco, Erica Curti, Arianna Sartori, Simone Cepparulo, Girolama Alessandra Marfia, Carolina Gabri Nicoletti, Antonio Carotenuto, Viviana Nociti, Francesca Caleri, Maria Pia Sormani, Alessio Signori

doi : 10.1177/13524585211005657

First Published April 15, 2021; pp. 93–101

Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity.

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Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis

Zoë YGJ van Lierop, Luuk Wieske, Marleen JA Koel-Simmelink, Madhurima Chatterjee, Iris Dekker, Cyra E Leurs, Eline AJ Willemse, Bastiaan Moraal, Frederik Barkhof, Filip Eftimov, Bernhard MJ Uitdehaag, Joep Killestein, Charlotte E Teunissen

doi : 10.1177/13524585211010097

First Published April 23, 2021; pp. 102–110

Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS).

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Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies

Nicola De Stefano, Maria Pia Sormani, Gavin Giovannoni, Kottil Rammohan, Thomas Leist, Patricia K Coyle, Fernando Dangond, Birgit Keller, Nektaria Alexandri, Andrew Galazka

doi : 10.1177/13524585211010294

First Published May 10, 2021; pp. 111–120

In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study of patients with relapsing-remitting multiple sclerosis, treatment with cladribine tablets 3.5 mg/kg (CladT) significantly reduced the annualised relapse rate (ARR) versus placebo; this effect was sustained in CLARITY Extension, without further treatment.

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Aging with multiple sclerosis: A longitudinal study of physical function, mental health, and memory in two cohorts of US women

Marianna Cortese, Kjetil Bjornevik, Tanuja Chitnis, Alberto Ascherio, Kassandra L Munger

doi : 10.1177/13524585211007739

First Published April 16, 2021; pp. 121–131

It is unknown how individuals with multiple sclerosis (MS) age compared to unaffected peers.

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Impact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey

Emilio Portaccio, Mattia Fonderico, Bernhard Hemmer, Tobias Derfuss, Bruno Stankoff, Krzysztof Selmaj, Mar Tintorè, Maria Pia Amato

doi : 10.1177/13524585211005339

First Published March 25, 2021; pp. 132–138

The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS).

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Depression readmission risk is elevated in multiple sclerosis compared to other chronic illnesses

Emily M Schorr, Daniel Kurz, Kyle C Rossi, Margaret Zhang, Anusha K Yeshokumar, Nathalie Jette, Mandip S Dhamoon

doi : 10.1177/13524585211051316

First Published November 17, 2021; pp. 139–148

Assess readmissions for depression or suicide attempt (SA) after MS admission versus other chronic inflammatory illnesses.

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Optic chiasm involvement in AQP-4 antibody–positive NMO and MOG antibody–associated disorder

Deena Tajfirouz, Tanyatuth Padungkiatsagul, Shannon Beres, Heather E Moss, Sean Pittock, Eoin Flanagan, Amy Kunchok, Shailee Shah, M Tariq Bhatti, John J Chen

doi : 10.1177/13524585211011450

First Published May 12, 2021; pp. 149–153

Optic neuritis (ON) is often the presenting symptom in inflammatory central nervous system demyelinating disorders.

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Mild gray matter atrophy in patients with long-standing multiple sclerosis and favorable clinical course

Rosa Cortese, Marco Battaglini, Francesca Parodi, Maria Laura Stromillo, Emilio Portaccio, Lorenzo Razzolini, Antonio Giorgio, Maria Pia Sormani, Maria Pia Amato, Nicola De Stefano

doi : 10.1177/13524585211019650

First Published June 8, 2021; pp. 154–159

The mechanisms responsible for the favorable clinical course in multiple sclerosis (MS) remain unclear. In this longitudinal study, we assessed whether magnetic resonance imaging (MRI)-based changes in focal and diffuse brain damage are associated with a long-term favorable MS diseases course. We found that global brain and gray matter (GM) atrophy changes were milder in MS patients with long-standing disease (⩾30 years from onset) and favorable (no/minimal disability) clinical course than in sex-age-matched disable MS patients, independently of lesions accumulation. Data showed that different trajectories of volume changes, as reflected by mild GM atrophy, may characterize patients with long-term favorable evolution.

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Pediatric paraneoplastic neuromyelitis optica spectrum disorder associated with ovarian teratoma

Lauren Tardo, Cynthia Wang, Veena Rajaram, Benjamin M Greenberg

doi : 10.1177/13524585211037582

First Published August 23, 2021; pp. 160–163

Neuromyelitis optica spectrum disorder is an inflammatory condition of the central nervous system typically manifesting as myelitis, optic neuritis, and/or area postrema syndrome. Here, we present a pediatric patient who developed symptoms consistent with area postrema syndrome with positive anti-aquaporin-4 (AQP4) antibodies who was also found to have an ovarian teratoma. Pathological specimens revealed the presence of aquaporin-4. This was felt to be the antigenic trigger that led to the patient’s condition. She suffered no further clinical attacks and seroconverted to negative AQP4 status upon teratoma removal. This case varies from others, in that the paraneoplastic presentation occurred in a pediatric patient and in that the patient has not required maintenance immunotherapy after teratoma removal.

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Aquaporin-4 antibody neuromyelitis optica spectrum disorder: A paraneoplastic disease?

Omar Abdel-Mannan, Yael Hacohen

doi : 10.1177/13524585211039755

First Published August 23, 2021; pp. 163–164

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SARS-CoV-2 antibodies in multiple sclerosis patients depending on the vaccine mode of action?

Paulus S Rommer, Gabriel Bsteh, Thomas Berger, Uwe Klaus Zettl

doi : 10.1177/13524585211039128

First Published August 13, 2021; pp. 165–167

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