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  1. Article ; Online: Re-thinking race and geography in multiple sclerosis.

    Ontaneda, Daniel / Amezcua, Lilyana

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2023  Volume 30, Issue 1, Page(s) 16–18

    MeSH term(s) Humans ; Multiple Sclerosis/epidemiology ; Geography
    Language English
    Publishing date 2023-10-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/13524585231205969
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  2. Article ; Online: Progressive Multiple Sclerosis.

    Ontaneda, Daniel

    Continuum (Minneapolis, Minn.)

    2019  Volume 25, Issue 3, Page(s) 736–752

    Abstract: Purpose of review: This article provides an update on progressive forms of multiple sclerosis (MS), with a focus on pathogenic mechanisms, clinical features, imaging features, and recent therapeutic advances.: Recent findings: Progressive forms of MS ...

    Abstract Purpose of review: This article provides an update on progressive forms of multiple sclerosis (MS), with a focus on pathogenic mechanisms, clinical features, imaging features, and recent therapeutic advances.
    Recent findings: Progressive forms of MS are identified by a history of progressive accrual of disability independent of relapse, but they share many biological, clinical, and MRI features with relapsing MS. Both relapses and new lesions can occur in the context of progressive MS, and establishing when the transition from relapsing to progressive MS occurs is often difficult. Several pathogenic mechanisms coexist in progressive MS. Targeting inflammation in both primary and secondary progressive MS appears to reduce the accumulation of disability.
    Summary: Progressive MS remains a diagnostic challenge, and the pathogenesis underlying progression is complex. Significant overlap in the biology and clinical and imaging features of progressive MS exists with relapsing forms of the disease. The use of disease-modifying and symptomatic treatments may improve the quality of life for patients with progressive MS.
    MeSH term(s) Adult ; Aged ; Antibodies, Monoclonal, Humanized/administration & dosage ; Disease Progression ; Female ; Humans ; Immunologic Factors/administration & dosage ; Immunosuppressive Agents/administration & dosage ; Male ; Multiple Sclerosis, Chronic Progressive/diagnostic imaging ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging ; Multiple Sclerosis, Relapsing-Remitting/drug therapy
    Chemical Substances Antibodies, Monoclonal, Humanized ; Immunologic Factors ; Immunosuppressive Agents ; ocrelizumab (A10SJL62JY)
    Language English
    Publishing date 2019-06-20
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1538-6899
    ISSN (online) 1538-6899
    DOI 10.1212/CON.0000000000000727
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  3. Article ; Online: Slowly Expanding Lesions: A New Target for Progressive Multiple Sclerosis Trials?

    Simmons, Sarah B / Ontaneda, Daniel

    Neurology

    2022  Volume 98, Issue 17, Page(s) 699–700

    MeSH term(s) Brain ; Humans ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis, Chronic Progressive/drug therapy
    Language English
    Publishing date 2022-03-11
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000200230
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  4. Article ; Online: Incorporating the Central Vein Sign Into the Diagnostic Criteria for Multiple Sclerosis.

    Ontaneda, Daniel / Cohen, Jeffrey A / Sati, Pascal

    JAMA neurology

    2023  Volume 80, Issue 7, Page(s) 657–658

    MeSH term(s) Humans ; Multiple Sclerosis/diagnostic imaging ; Veins ; Magnetic Resonance Imaging
    Language English
    Publishing date 2023-04-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2702023-X
    ISSN 2168-6157 ; 2168-6149
    ISSN (online) 2168-6157
    ISSN 2168-6149
    DOI 10.1001/jamaneurol.2023.0717
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  5. Article ; Online: Making Sure Multiple Sclerosis Counts and Is Counted for All-An Update on Multiple Sclerosis Prevalence by Race and Ethnicity in the United States.

    Rotstein, Dalia L / Gyang, Tirisham V / Ontaneda, Daniel

    JAMA neurology

    2023  Volume 80, Issue 7, Page(s) 667–669

    MeSH term(s) Humans ; Ethnicity ; Multiple Sclerosis/epidemiology ; Multiple Sclerosis/ethnology ; Prevalence ; United States/epidemiology ; Racial Groups
    Language English
    Publishing date 2023-05-15
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2702023-X
    ISSN 2168-6157 ; 2168-6149
    ISSN (online) 2168-6157
    ISSN 2168-6149
    DOI 10.1001/jamaneurol.2023.0469
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  6. Article ; Online: The benefits and risks of escalation versus early highly effective treatment in patients with multiple sclerosis.

    Morgan, Annalisa / Tallantyre, Emma / Ontaneda, Daniel

    Expert review of neurotherapeutics

    2023  Volume 23, Issue 5, Page(s) 433–444

    Abstract: Introduction: Multiple sclerosis is a chronic, demyelinating, inflammatory, and neurodegenerative disease of the central nervous system that affects over 2 million people worldwide. Considerable advances have been made in the availability of disease ... ...

    Abstract Introduction: Multiple sclerosis is a chronic, demyelinating, inflammatory, and neurodegenerative disease of the central nervous system that affects over 2 million people worldwide. Considerable advances have been made in the availability of disease modifying therapies for relapsing-remitting multiple sclerosis since their introduction in the 1990s. This has led to debate regarding the optimal first-line treatment approach: a strategy of escalation versus early highly effective treatment.
    Areas covered: This review defines the strategies of escalation and early highly effective treatment, outlines the pros and cons of each, and provides an analysis of both the current literature and expected future directions of the field.
    Expert opinion: There is growing support for using early highly effective treatment as the initial therapeutic approach in relapsing-remitting multiple sclerosis. However, much of this support stems from observational real-world studies that use historic data and lack safety outcomes or randomized control trials that compare individual high versus low-moderate efficacy therapies, instead of the approaches themselves. Randomized control trials (DELIVER-MS, TREAT-MS) are needed to systemically and prospectively compare contemporary escalation versus early highly effective treatment approaches.
    MeSH term(s) Humans ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Neurodegenerative Diseases ; Treatment Outcome ; Risk Assessment
    Language English
    Publishing date 2023-05-15
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 2112534-X
    ISSN 1744-8360 ; 1473-7175
    ISSN (online) 1744-8360
    ISSN 1473-7175
    DOI 10.1080/14737175.2023.2208347
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  7. Article ; Online: Differentiating multiple sclerosis from non-specific white matter changes using a convolutional neural network image classification model.

    Amin, Moein / Nakamura, Kunio / Ontaneda, Daniel

    Multiple sclerosis and related disorders

    2023  Volume 82, Page(s) 105420

    Abstract: Background: The diagnosis of multiple sclerosis (MS) relies heavily on neuroimaging with magnetic resonance imaging (MRI) and exclusion of mimics. This can be a challenging task due to radiological overlap in several disorders and may require ancillary ... ...

    Abstract Background: The diagnosis of multiple sclerosis (MS) relies heavily on neuroimaging with magnetic resonance imaging (MRI) and exclusion of mimics. This can be a challenging task due to radiological overlap in several disorders and may require ancillary testing or longitudinal follow up. One of the most common radiological MS mimickers is non-specific white matter disease (NSWMD). We aimed to develop and evaluate models leveraging machine learning algorithms to help distinguish MS and NSWMD.
    Methods: All adult patients who underwent MRI brain using a demyelinating protocol with available electronic medical records between 2015 and 2019 at Cleveland Clinic affiliated facilities were included. Diagnosis of MS and NSWMD were assessed from clinical documentation. Those with a diagnosis of MS and NSWMD were matched using total T2 lesion volume (T2LV) and used to train models with logistic regression and convolutional neural networks (CNN). Performance metrices were reported for each model.
    Results: A total of 250 NSWMD MRI scans were identified, and 250 unique MS MRI scans were matched on T2LV. Cross validated logistic regression model was able to use 20 variables (including spinal cord area, regional volumes, and fractions) to predict MS compared to NSWMD with 68.0% accuracy while the CNN model was able to classify MS compared to NSWMD in two independent validation and testing cohorts with 77% and 78% accuracy on average.
    Conclusion: Automated methods can be used to differentiate MS compared to NSWMD. These methods can be used to supplement currently available diagnostic tools for patients being evaluated for MS.
    MeSH term(s) Adult ; Humans ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/pathology ; White Matter/diagnostic imaging ; White Matter/pathology ; Magnetic Resonance Imaging/methods ; Neural Networks, Computer ; Neuroimaging/methods ; Leukoencephalopathies/pathology ; Brain/diagnostic imaging ; Brain/pathology
    Language English
    Publishing date 2023-12-31
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2645330-7
    ISSN 2211-0356 ; 2211-0348
    ISSN (online) 2211-0356
    ISSN 2211-0348
    DOI 10.1016/j.msard.2023.105420
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  8. Article: Thalamic Injury and Cognition in Multiple Sclerosis.

    Amin, Moein / Ontaneda, Daniel

    Frontiers in neurology

    2021  Volume 11, Page(s) 623914

    Abstract: Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, ... ...

    Abstract Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, as it undergoes volume loss in different MS subtypes and is involved in the earliest form of the disease, radiologically isolated syndrome. The thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been associated with a variety of clinical manifestations in MS, including fatigue, movement disorders, pain, and cognitive impairment (CI). Similar to thalamic volume loss, CI is seen from the earliest stages of MS and is potentially one of the most debilitating manifestations of the disease. The thalamus, particularly the dorsomedial nucleus as part of the basolateral limbic circuit and anterior thalamic nuclei through connections with the prefrontal cortex, has been shown to be involved in CI. Specifically, several cognitive performance measures such as processing speed and memory correlate with thalamic volume. Thalamic atrophy is one of the most important predictors of CI in MS, and both thalamic volume, diffusion tensor imaging measures, and functional activation correlate with the degree of CI in MS. Although the exact mechanism of thalamic atrophy is not well-understood, it is hypothesized to be secondary to degeneration following white matter injury resulting in secondary neurodegeneration and neuronal loss. The thalamus may represent an ideal biomarker for studies aiming to test neuroprotective or restorative therapies aimed at cognition.
    Language English
    Publishing date 2021-02-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2020.623914
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  9. Article ; Online: Inadequate outcome measures are the biggest impediment to successful clinical trials in progressive MS - Commentary.

    Ontaneda, Daniel

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2016  Volume 23, Issue 4, Page(s) 508–509

    MeSH term(s) Humans ; Multiple Sclerosis, Chronic Progressive ; Outcome Assessment (Health Care)
    Language English
    Publishing date 2016-10-11
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/1352458516674368
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  10. Article ; Online: Clinical trials for progressive multiple sclerosis: progress, new lessons learned, and remaining challenges.

    Chataway, Jeremy / Williams, Thomas / Li, Vivien / Marrie, Ruth Ann / Ontaneda, Daniel / Fox, Robert J

    The Lancet. Neurology

    2024  Volume 23, Issue 3, Page(s) 277–301

    Abstract: Despite the success of disease-modifying treatments in relapsing multiple sclerosis, for many individuals living with multiple sclerosis, progressive disability continues to accrue. How to interrupt the complex pathological processes underlying ... ...

    Abstract Despite the success of disease-modifying treatments in relapsing multiple sclerosis, for many individuals living with multiple sclerosis, progressive disability continues to accrue. How to interrupt the complex pathological processes underlying progression remains a daunting and ongoing challenge. Since 2014, several immunomodulatory approaches that have modest but clinically meaningful effects have been approved for the management of progressive multiple sclerosis, primarily for people who have active inflammatory disease. The approval of these drugs required large phase 3 trials that were sufficiently powered to detect meaningful effects on disability. New classes of drug, such as Bruton tyrosine-kinase inhibitors, are coming to the end of their trial stages, several candidate neuroprotective compounds have been successful in phase 2 trials, and innovative approaches to remyelination are now also being explored in clinical trials. Work continues to define intermediate outcomes that can provide results in phase 2 trials more quickly than disability measures, and more efficient trial designs, such as multi-arm multi-stage and futility approaches, are increasingly being used. Collaborations between patient organisations, pharmaceutical companies, and academic researchers will be crucial to ensure that future trials maintain this momentum and generate results that are relevant for people living with progressive multiple sclerosis.
    MeSH term(s) Humans ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Immunomodulation ; Forecasting
    Language English
    Publishing date 2024-01-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2081241-3
    ISSN 1474-4465 ; 1474-4422
    ISSN (online) 1474-4465
    ISSN 1474-4422
    DOI 10.1016/S1474-4422(24)00027-9
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