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Human studies revealed thinner myelin sheaths in CD59-deficient patients, indicative of a process of segmental demyelination followed by remyelination.

Preclinical Study Links CD59 Deficiency to Demyelination and Conduction Blocks

Videos

Neurology News Network. for the week ending December 21, 2024. [WATCH TIME: 4 minutes]

FDA Places Hold on CONNECT2-EDO51, Sevasemten Meets End Point in Becker, Tolebrutinib Gets Breakthrough Therapy Designation

Take 5 minutes to catch up on NeurologyLive®'s highlights from the week ending December 20, 2024. 

NeurologyLive® Friday 5 — December 20, 2024

Managing ALS, particularly its respiratory complications, requires a collaborative multidisciplinary team—including neurologists, pulmonologists, and respiratory therapists—working together to address the complexities of respiratory failure, the leading cause of death in these patients.

Breathing Life Into ALS Care: The Vital Role of Multidisciplinary Teams

Assistant professor of neurosurgery and neuroscience at Mayo Clinic Arizona

The assistant professor of neurosurgery and neuroscience at Mayo Clinic Arizona discussed an ongoing early-stage study assessing the therapeutic potential of NRTX-1001 nerve cell therapy in drug-resistant unilateral mesial temporal lobe epilepsy. [WATCH TIME: 5 minutes]

Studying Nerve Cell Therapy NRTX-1001 to Treat Mesial Temporal Lobe Epilepsy: Jonathan Parker, MD, PhD

, has been with the team since September 2022. Follow her on Twitter 

The program assembles a collaborative team of in-house and external experts in research, clinical care, and regulatory affairs to navigate gene therapy programs through the drug development process.

FDA Grants MDA Kickstart Program Rare Pediatric Disease Designation and Orphan Drug Designation in Congenital Myasthenic Syndrome

IJMSC Insights offers a closer look at the latest research and the people behind it from the community of the International Journal of Multiple Sclerosis Care (IJMSC) and the Consortium of Multiple Sclerosis Centers (CMSC).

IJMSC Insights: Blanca De Dios Perez on Employment and Multiple Sclerosis

Pediatric epilepsy specialist at University of California, San Francisco.

At AES 2024, a duo of pediatric epilepsy specialists discussed how implementation science, validated blood biomarkers, and cross-disciplinary collaboration are advancing epilepsy care and closing research gaps. [WATCH TIME: 3 minutes]

Advancing Epilepsy Research Through Implementation Science and Biomarkers: Adam Numis, MD; Laura Kirkpatrick, MD

The multiple sclerosis condition center is a resource for clinical news on the diagnosis, treatment, and management of multiple sclerosis. | NeurologyLive.


Multiple Sclerosis | Clinical Neurology News | NeurologyLive

NeurologyLive is your direct connection to the latest neurology news and interviews with expert neurologists in multimedia formats.

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 MS Disease Spotlight page offers specific updates and coverage on the latest expert conversations and data readouts related to the treatment and management of patients with multiple sclerosis and demyelinating disorders.

 to subscribe on your favorite streaming service.

The Mind Moments podcast features exclusive interviews with leaders in the field discussing the latest research and disease management strategies across the breadth of neurology, including epilepsy, multiple sclerosis, Parkinson disease, dementia, sleep disorders, and more.

In this episode, "Understanding Major Changes to New McDonald Criteria for Multiple Sclerosis," Daniel Ontaneda, MD, PhD, a staff member of the Cleveland Clinic Mellen Center for Multiple Sclerosis, provided an in-depth overview on the new McDonald criteria to diagnose multiple sclerosis (MS), which was presented at the 

40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)

. Ontaneda, who also serves as an assistant professor of neurology, discussed the most notable changes to the criteria and how it may help towards improving rates of misdiagnosis and missed diagnosis. He spoke on the incorporation of new biomarkers, such as central vein sign and paramagnetic rim lesions, and the ability to diagnose MS in stages before clinical presentation shows. Furthermore, Ontaneda gave some perspective on the areas of the new criteria that will take some time to adjust to, as well as how these criteria may change the philosophical perspective of the disease as a whole.


The stories featured in this week's Neurology News Minute, which will give you quick updates on the following developments in neurology, are further detailed here:

Potential Regulatory Submission for Inebilizumab in Myasthenia Gravis Following Positive Phase 3 MINT Data

Parkinson Agent Tavapadon Meets Primary and Secondary End Points as Monotherapy in Phase 3 TEMPO-1 Trial

Sage Therapeutics and Biogen Officially Announce Ending of SAGE-324 Program in Essential Tremor

 – Focus and direction of new diagnostic criteria

 – Overviewing specific changes to McDonald criteria

 – Approach to diagnosing pre-MS; treating radiologically isolated syndrome earlier

 – Incorporation of new biomarkers, central vein sign, paramagnetic rim lesions, OCT

 – Unanswered questions/challenges left out of the diagnostic criteria

 to subscribe to the Mind Moments podcast. Be sure to leave a rating and review for the show. Thanks for listening!

Hoping to listen on your favorite podcast app? See below:

European Committee for Treatment and Research in Multiple Sclerosis Congress (ECTRIMS)

Mind Moments®, a podcast from NeurologyLive®, brings you an exclusive interview with Daniel Ontaneda, MD, PhD. [LISTEN TIME: 27 minutes]

Episode 125: Understanding Major Changes to New McDonald Criteria for Multiple Sclerosis

The Mind Moments podcast features exclusive interviews with leaders in the field discussing the latest research and disease management strategies across the breadth of neurology, including epilepsy, multiple sclerosis (MS), Parkinson disease, dementia, sleep disorders, and more.

Episode 47, "Incorporating Physical Therapy Into MS Care," features an exclusive interview with Patricia Bobryk, MHS, PT, MSCS, ATP, physical therapist, UC Health, and cochair, 

International Organization of MS Rehabilitation Therapists (IOMSRT)

. Bobryk shared her insight into the clinical care of MS from the perspective of a rehabilitative specialist, and the importance of including physical therapy approaches as part of the multidisciplinary approach to care as early as possible to ensure more beneficial long-term outcomes for patients, also speaking to the latest advances and developments in rehabilitative medicine.

The stories feature in this week's Neurology News Minute, which will give you quick updates on the following developments in neurology, are further detailed here:

Noncontact Boxing Exercise Assessed for Parkinson Disease Benefit

Opicapone Demonstrates Small Benefit for Sleep in Parkinson Disease

Amylyx Announces Plans to Submit NDA for AMX0035 for ALS

Episode Breakdown

"Mind Moments," a podcast from NeurologyLive, brings you an exclusive interview with Patricia Bobryk, MHS, PT, MSCS, ATP.

Episode 47: Incorporating Physical Therapy Into MS Care

Episode 38, "Advancing MS Care and Awareness," features an interview with Barry Hendin, MD, clinical professor, University of Arizona; director, Multiple Sclerosis Clinic, Banner University Medical Center; and chief medical officer, Multiple Sclerosis Association of America. He shared his perspective on the recent World MS Day on May 30, the impact awareness efforts have had on care, and how treatment has evolved during his time as a multiple scleorsis (MS) physician.

"Mind Moments," a podcast from NeurologyLive, brings you an exclusive interview with Barry Hendin, MD.

Episode 38: Advancing MS Care and Awareness

Those on intermittent calorie restriction showed a notable improvement in the mental subscale of the MSIS Score and a significant reduction in cognitive and psychosocial fatigue.

Calorie Restriction is Safe in Multiple Sclerosis, With Positive Impacts on Cognition and Fatigue

Findings from the ongoing PERSEUS phase 3 study of tolebrutinib in primary progressive multiple sclerosis are anticipated to be reported in the second half of 2025.

FDA Grants Tolebrutinib Breakthrough Therapy for Nonrelapsing Secondary Progressive Multiple Sclerosis

Obesity was associated with faster progression of disability, including a higher risk of reaching higher EDSS scores, suggesting that increased body weight contributes to MS severity over time.

Case-Control Study Highlights Significant Negative Effects of Obesity in Patients With Multiple Sclerosis

A new feature, in collaboration with NeurologyLive® and the International Journal of MS Care, brings perspectives from both the research and clinical community on women’s brain health as a subspecialty in neurology.

A Subspecialty for Half the World’s Population: Women’s Neurology

Here's the latest multidisciplinary multiple sclerosis (MS) research from the International Journal of MS Care.

Research from IJMSC November 2024

Panelists discuss how disease-modifying therapies (DMTs) like dimethyl fumarate, fingolimod, and cladribine demonstrate potential blood-brain barrier penetration, offering neuroprotective mechanisms. While these therapies show promise in mitigating cognitive decline, their impacts vary, highlighting the complex interplay among neuroinflammation, immune modulation, and cognitive preservation in multiple sclerosis management.

Exploring DMTs: Blood-Brain Barrier Penetration and Cognitive Health Benefits

Video content above is prompted by the following:

Which of the DMTs can penetrate the blood-brain barrier and have the potential to impact brain health directly?

What is our understanding of the impact of various DMTs on cognitive health?

Disease-modifying therapies (DMTs) for multiple sclerosis (MS) vary in their ability to penetrate the blood-brain barrier (BBB) and impact brain health. Some DMTs, such as fingolimod, siponimod, and natalizumab, have demonstrated the ability to cross the BBB and potentially influence cognitive health. The impact of DMTs on cognitive health is an area of ongoing research, with some studies suggesting potential benefits in slowing cognitive decline. However, the extent of these effects and the mechanisms involved remain under investigation, necessitating further studies to elucidate their cognitive benefits.

Panelists discuss how in managing multiple sclerosis (MS), clinicians must adopt a comprehensive approach to progressive irreversible reductions in activity (PIRA) that prioritizes early detection, transparent communication, and patient empowerment. By integrating regular cognitive assessments, providing compassionate and clear explanations, and emphasizing proactive management strategies, physicians can help patients navigate the complex cognitive landscape of MS, ultimately preserving quality of life and fostering patient resilience in the face of neurological challenges.

Addressing PIRA in Clinical Practice and Patient Conversations

Considering this data, how should MS specialists and other clinicians be thinking about PIRA in everyday clinical practice?

How should physicians communicate PIRA with patients?

Why is it important to think about cognitive health in MS and to talk to patients about it?

Cladribine's impact on disability accumulation, including PIRA, relapse-associated worsening, and confirmed disability accumulation, underscores the significance of early therapy initiation. The MAGNIFY-MS study reveals that both treatment-naive and previously treated patients benefit from cladribine, with reduced disability progression. Comparatively, high-efficacy DMTs like ocrelizumab, ofatumumab, and S1P receptor modulators also demonstrate efficacy in managing PIRA. These therapies show promise in mitigating disability accumulation, emphasizing the need for timely intervention. The data suggest that early and effective treatment strategies are crucial in managing disease progression and improving patient outcomes.

The manager of the BARLO MS education program at St. Michael's Hospital highlighted the significance of recognition, the pivotal role of nurses in multiple sclerosis care, and the lasting impact of mentorship and advocacy. 

Honoring the Impact of Recognition and Advocacy in MS Care: Aprile Royal, RN, BA, MEd

"I think we all do a little more, go the extra mile, listen more, and take things to heart a little more when we feel appreciated across the board. An award like this goes a long way toward creating that sense of appreciation and inspiring us to do more."

Consortium of Multiple Sclerosis Centers (CMSC)

, the Giants of Multiple Sclerosis award honors trailblazers, innovators, and visionaries acknowledged by their colleagues for their outstanding contributions to multiple sclerosis (MS) research. Established in 2021, individuals named to this prestigious program have made significant contributions to the field. Out of numerous nominations, 

 have been selected to join the esteemed group of 2024 honorees.

The advisory board, who determine the finalists in each category, consists of MS health care professionals, each recognized for their significant contributions to the field. They offer guidance to 

 as it continues to develop and grow the recognition program. The selection committee, comprising over 30 MS professionals, then votes to determine the inductee from each category. At the 

, held May 29 to June 1, in Nashville, Tennessee, Aprile Royal, RN, BA, MEd, manager of the BARLO MS education program at St. Michael's Hospital, received recognition for the award in nursing.

, Royal shared her reaction to being chosen by her peers as a "Giant" in the field of MS. She also described her time at the award ceremony in Nashville and her favorite portion of the event. In addition, she talked about her most proud career moment if she had to choose one and the most fulfilling part of working with patients with MS. She also spoke about the importance of recognizing others for their life's work with an award like this and explained why others should nominate their colleagues. Furthermore, she expressed what 

, meant to her and the wider MS community.

Have you nominated your Giant of Multiple Sclerosis? Help us recognize and celebrate pioneers, innovators, and leaders in MS. 

The manager of the BARLO MS education program at St. Michael's Hospital highlighted the significance of recognition, the pivotal role of nurses in multiple sclerosis care, and the lasting impact of mentorship and advocacy. [WATCH TIME: 5 minutes]

SAP Partners

Panelists discuss how the MAGNIFY-MS study underscores the significance of early, aggressive multiple sclerosis (MS) treatment with cladribine, demonstrating its potential to effectively mitigate disability progression through progression independent of relapse activity (PIRA) suppression in both treatment-naive and previously treated patient populations, with outcomes competitive with other high-efficacy disease-modifying therapies.

Disability Accumulation and Early Therapy: Insights from MAGNIFY-MS and High-Efficacy DMT Data

Stefano et al presented data on disability accumulation (PIRA, relapse-associated worsening, confirmed disability accumulation) with cladribine from the MAGNIFY-MS study that show the importance of early initiation of therapy. Please highlight disability accumulation in both treatment-naive and previously treated groups.

Please share an overview of PIRA data with other high-efficacy disease-modifying therapies (DMTs) (ocrelizumab, ofatumumab, S1P receptor modulators, etc).

Panelists discuss how recent investigations into progression independent of relapse activity (PIRA) in multiple sclerosis (MS) have revealed complex inflammatory signatures in cerebrospinal fluid and peripheral blood, with biomarkers like neurofilament light chain and pro-inflammatory cytokines showing promise in tracking neurodegeneration. The Swedish MS Registry’s findings suggest that early implementation of high-efficacy disease-modifying therapies may effectively delay or prevent PIRA progression, though these results require further robust, multicenter validation to definitively establish clinical significance and generalizability.

Biomarkers and Therapeutic Impact on PIRA

What is our understanding of biomarkers of PIRA? What do we know about inflammatory signatures in the cerebrospinal fluid and peripheral blood of patients with PIRA?

Findings from the Swedish MS Registry show that early use of high vs medium efficacy disease-modifying therapy may be effective in delaying or preventing PIRA. Are these differences meaningful? Do you have any concerns about this study?

Biomarkers of progression independent of relapse activity (PIRA) in multiple sclerosis (MS) are crucial for understanding disease mechanisms. Inflammatory signatures in cerebrospinal fluid and peripheral blood provide insights into PIRA's pathophysiology. The Swedish MS Registry suggests that early high-efficacy disease-modifying therapies (DMTs) may delay or prevent PIRA compared to medium-efficacy DMTs. These findings highlight the potential benefits of aggressive early treatment. However, concerns about study design, patient selection, and long-term outcomes warrant careful consideration to validate these results and ensure their applicability in clinical practice.

Panelists discuss how progression independent of relapse activity (PIRA) in multiple sclerosis (MS) represents continuous neurological decline unrelated to inflammatory events, distinct from relapse-associated worsening (RAW). Recent ECTRIMS 2024 presentations emphasized standardized evaluation methods to better understand disease progression and improve patient management strategies.

Understanding PIRA in MS: Key Insights and Advances From ECTRIMS 2024

Cognition and PIRA in MS have received a lot of attention in recent years.

Please provide an overview of PIRA and its potential impact on a patient’s quality of life.

How is PIRA evaluated? Discuss presentations from ECTRIMS 2024 by Muller and others about standardization of PIRA evaluation and why it might matter.

PIRA, or Progression Independent of Relapse Activity, is a concept in multiple sclerosis (MS) that highlights disease progression occurring without clinical relapses. It significantly impacts patients' quality of life by contributing to disability accumulation. Unlike Relapse-Associated Worsening (RAW), PIRA reflects a more insidious progression, often undetected by traditional relapse-focused assessments. Evaluating PIRA involves advanced imaging and clinical metrics, as discussed in ECTRIMS 2024 presentations. Standardizing PIRA evaluation is crucial for consistent monitoring and treatment strategies, potentially leading to improved patient outcomes and personalized therapeutic approaches.

Panelists discuss how modern multiple sclerosis (MS) management has evolved from symptomatic treatment to a proactive, personalized approach leveraging advanced biomarkers and sophisticated disease-modifying therapies. The focus has shifted toward early intervention, precise monitoring, and comprehensive disease control, significantly improving patient outcomes and quality of life.

The Impact of Biomarkers and Modern Disease-Modifying Therapies in MS

Please share how your management of MS has changed in recent years with the availability of biomarkers and highly efficacious disease-modifying therapies.

The management of multiple sclerosis (MS) has evolved significantly with the advent of biomarkers and advanced disease-modifying therapies (DMTs). Biomarkers have enhanced diagnostic precision, enabling earlier and more accurate identification of MS, which facilitates timely intervention. The introduction of highly efficacious DMTs has transformed treatment paradigms, offering improved control over disease progression and reducing relapse rates. These advancements have allowed for more personalized treatment strategies, optimizing patient outcomes. The integration of these innovations into clinical practice underscores a shift towards a more proactive and tailored approach in MS management.

The William S. and Lois Stiles Edgerly Professor of Neurology at Yale School of Medicine talked about the ongoing evolution of multiple sclerosis diagnostic criteria and the importance of comprehensive testing to guide early intervention and improve outcomes.

Evolution of Multiple Sclerosis Diagnostic Criteria and the Role of Spinal Taps: David A. Hafler, MD, FANA

“Ultimately, I should point out that the diagnosis of [multiple sclerosis] is a pathological diagnosis, and what we do clinically is add various measurements that increase the probability of making an accurate diagnosis.”

The McDonald Diagnostic Criteria, first introduced in 2001 and updated most recently in 2017, offers neurologists a framework designed to enhance the accuracy and speed of multiple sclerosis (MS) diagnoses. Since the last update, an expert committee has worked on further updates to incorporate recent advancements in the understanding of MS, with the goal of enabling earlier identification of the disease to improve patient outcomes. The newer updated revision emphasizes a deeper understanding of the biological mechanisms of MS, facilitating more precise assessments alongside clinical symptom evaluation.

, held September 18-20 in Copenhagen, Denmark, key recommendations from the new revision were presented. These include the adoption of advanced diagnostic methods and the development of age-specific criteria to more accurately diagnose MS in both younger and older populations. The aim of these changes is to enhance diagnostic precision by examining biomarkers of MS-related damage that go beyond observable symptoms. The committee is preparing a peer-reviewed publication of the finalized updates, expected by early 2025.

, the William S. and Lois Stiles Edgerly Professor of Neurology at 

 to discuss how advancements in technologies have improved the diagnostic criteria for MS, and how this has impacted the clinical practice. Hafler, who also serves as the Neurologist-in-Chief at the Yale-New Haven Hospital, talked about why the term "definitive" MS should be discarded, and how this would reflect the evolving approach to MS diagnosis. Moreover, he spoke about how age affects the accuracy of an MS diagnosis, and how the approach differs when diagnosing younger versus older patients.

REFERENCES
1. Montalban X. 2024 Revisions of the McDonald Criteria. Presented at ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. Scientific Session 1: New diagnostic criteria.
2. European Committee for Treatment and Research in MS. McDonald Diagnostic Criteria. Accessed November 12, 2024. https://ectrims.eu/mcdonald-diagnostic-criteria#

The William S. and Lois Stiles Edgerly Professor of Neurology at Yale School of Medicine talked about the ongoing evolution of multiple sclerosis diagnostic criteria and the importance of comprehensive testing to guide early intervention and improve outcomes. [WATCH TIME: 5 minutes]

Multiple Sclerosis

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