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Take 5 minutes to catch up on NeurologyLive®'s highlights from the week ending April 19, 2024. 

NeurologyLive® Friday 5 — April 19, 2024

Patients experienced improvements in ON/OFF time and motor function, with favorable tolerability, paving the way for a phase 2 trial.

Parkinson Gene Therapy AB-1005 Continues to Show Promising Results at 18 Months

Videos

The instructor in neurology at Brigham and Women's Hospital talked about research exploring takotsubo syndrome, a heart condition often triggered by emotional or physical stressors, and its relationship with brain lesions. [WATCH TIME: 5 minutes]

Takotsubo Syndrome and the Brain-Heart Connection: Frederic Schaper, MD, PhD

Neal K. Shah, CEO of CareYaya Health Technologies, an AI innovator in neurological care, discussed how technology is poised to transform the fight against Parkinson, with the potential to improve millions of lives and advance health equity.

The AI Revolution That Could Slow Parkinson In Its Tracks

Chief of the Division of MS and Neuroimmunology at UConn Health.

The chief of the Division of MS and Neuroimmunology at UConn Health talked about the unevenly distributed progress in multiple sclerosis care, impacting minority populations who often face worse disease outcomes. [WATCH TIME: 6 minutes]

Advancing MS Care for Minority Populations Using the VISIBL-MS Bilingual Framework: Jaime Imitola, MD

Dermatology resident, University Hospitals.

A trio of experts from university hospitals discussed a study that aimed to uncover the prevalence and associations of limb swelling in patients with Dravet syndrome in hopes of improving care. [WATCH TIME: 5 minutes]

Investigating Limb Swelling in Patients With Dravet Syndrome: Mandy Alhajj, DO, James Dolbow, DO & Neel Fotedar, MD

The executive vice president of research at National MS Society talked about the Dystel Prize which is presented at AAN to a recognized individual who promotes further advancements in understanding and treating MS. [WATCH TIME: 3 minutes]

Recognizing Excellence in Multiple Sclerosis Research, the Dystel Prize: Bruce Bebo, PhD

Director of the Allegheny Multiple Sclerosis Treatment Center at Allegheny General Hospital.

The director of the Allegheny Multiple Sclerosis Treatment Center at Allegheny General Hospital discussed exploring the potential role of BTK inhibitors and advanced MRI techniques to address smoldering multiple sclerosis. [WATCH TIME: 10 minutes]

New Insights into BTK Inhibitors and MRI Techniques for Smoldering MS: Thomas F. Scott, 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

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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.

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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

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

Disease Spotlight: Multiple Sclerosis

"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

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.

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

Elizabeth Miller, MA, the manager of health literacy at the National MS Society, discussed the impact of health literacy in the multiple sclerosis community. 

Advancing Equity and Inclusion: Health Literacy for the MS Community and Beyond

As part of our monthly clinician spotlight, NeurologyLive® highlighted multiple sclerosis expert Scott Newsome, DO, MSCS, FAAN, FANA, director of the Stiff Person Syndrome Center and professor of neurology at Johns Hopkins Medicine. 

NeurologyLive® Clinician of the Month Spotlight: Scott Newsome, DO, MSCS, FAAN, FANA

A feature on NeurologyLive®, 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).

Are Apps the Answer? Access in Multiple Sclerosis Care

In a paradigm with many options, once multiple sclerosis is confirmed as a patient’s diagnosis, physicians are left with 1 question: What do we choose for long-term treatment? 

Navigating Treatment Decision-Making in Multiple Sclerosis

Here's the latest multidisciplinary MS research published online first in the International Journal of MS Care.

IJMSC Online First: March 2024

Jaime Imitol, MD, talked about the unevenly distributed progress in multiple sclerosis care, impacting minority populations.

Advancing MS Care for Minority Populations Using the VISIBL-MS Bilingual Framework: Jaime Imitol, MD

"By increasing self-agency in patients and raising awareness of early red flags and warning signs of MS, we can improve the number of patients who seek timely medical care."

Early detection in multiple sclerosis (MS) is important in the age of disease modifying therapies (DMT) and improved diagnostic criteria. Research shows that there is a lack of public awareness about MS, which results in delays of DMT initiation. This negatively impacts demographics with increased risk of severe disease burden and increased health disparities, including the African American and Hispanic patient population.

 are effective for educating patients, families, and medical students about the early signs of stroke. Recently, investigators conducted a systematic review to determine the use of educational tools and mnemonics in MS education. After consulting with culturally competent bilingual physicians and patients, researchers then designed a mnemonic called 

 to encompass early signs of MS for medical students, general neurologists, and the population at large. This bilingual framework, which offers directions in English and Spanish, provides a novel structure for MS-specific awareness that addresses the interconnection between language, culture, health literacy, and health outcomes

2024 American Academy of Neurology (AAN) Annual Meeting

, held April 13-18, in Denver, Colorado, by senior author Jaime Imitola, MD, chief of the Division of MS and Neuroimmunology at UConn Health. Imitol sat down with 

 at the meeting to discuss steps that can be taken to increase awareness and understanding of MS among minority populations. He also spoke about how medical students and healthcare providers can be better equipped to support patients with the disease. Additionally, Imitol, who also serves as a professor of neurology, genetics and genome sciences, and neuroscience at University of Connecticut, talked about the main challenges in delivering equitable MS care to African American and Hispanic patients.

Click here for more coverage of AAN 2024.

REFERENCES
1. Patel S, Rafferty S, Aquino L, et al. VISIBL-MS: A Bilingual Educational Tool to Increase Awareness of Early Multiple Sclerosis in Diverse Populations. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
2. Patel S, Rafferty S, Aquino L, et al. VISIBL-MS: A bilingual educational framework to increase awareness of early multiple sclerosis. 

. 2024;30(4-5):585-593. doi:10.1177/13524585241228739

SAP Partners

Prashanth Rajarajan, MD, PhD, Brigham talked about the assessment of safety with checkpoint inhibitors for cancer treatment in patients with multiple sclerosis.

Safety of Cancer Treatment in Patients With Multiple Sclerosis: Prashanth Rajarajan, MD, PhD

"The checkpoint inhibitors seem to be safe from the perspective of not exacerbating the underlying neurologic condition."

Research shows an association between the use of immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs) as well as exacerbation of pre-existing autoimmune diseases. Although prior studies show that ICIs trigger relapses in patients with multiple sclerosis (MS), the incidence of ICI-induced MS activity is unclear. In a new interim analysis of  a study of patients with MS who were predominantly older and not on disease-modifying therapy (DMT), findings showed an unusual occurrence of MS relapses and disease progression following ICI treatment.

Investigators identified 38 patients with MS who were treated with ICIs, 13 (34%) of whom were on DMT immediately prior to ICI initiation and 8 who continued on DMT during ICI therapy. Presented at the 

, held April 13-18, in Denver, Colorado, by coauthor Prashanth Rajarajan, MD, PhD, and colleagues, the most common primary tumors were lung (n = 11) and melanoma (n = 10). Over a mean follow-up of 13 months after ICI initiation, 1 patient had a relapse after ICI treatment and 1 other patient had ongoing progressive disease. Notably, 2 patients (5%) had peripheral nervous system ICI irAEs and 12 (32%) had a nonneurologic ICI irAEs.

Rajarajan, neurology resident at Massachusetts General Brigham, sat down with 

 at the meeting to further discuss how the use of immune checkpoint inhibitors impact patients with pre-existing MS. He also talked about the rates of relapse or disease activity that occur in MS patients treated with checkpoint inhibitors. In addition, Rajarajan spoke about how the treatment approach should differ for patients with MS as opposed to other autoimmune conditions.

REFERENCES
1. Quinn C, Rajarajan P, Kopinsky H. Multi-institutional Study of Neurologic Outcomes in People with Multiple Sclerosis Who Are Treated with Immune Checkpoint Inhibitors for Oncologic Indications. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.

The neurology resident at Massachusetts General Brigham talked about assessing the safety of cancer treatments in patients with multiple sclerosis using checkpoint inhibitors. [WATCH TIME: 6 minutes] 

Safety of Cancer Treatments in Patients With Multiple Sclerosis: Prashanth Rajarajan, MD, PhD

Riley Bove, MD, talked about findings from an analysis that assessed the safety of ocrelizumab when administered close to pregnancy.

Pregnancy Outcomes of Maternal Exposure to Ocrelizumab: Riley Bove, MD

"From what we can gather from our best data, we don't see any major risk or safety signal [with ocrelizumab], whether that's about the pregnancy itself, or about how the babies are doing."

The United States prescription information advises for contraception with ocrelizumab (Ocrevus; Genentech) and for 6 months following the latest infusion; however, patients with multiple sclerosis (MS) may have pregnancies during this interval. In a new analysis, findings showed that 

 exposure to ocrelizumab did not increase risk of adverse pregnancy or infant outcomes compared with previous reports and an epidemiological background of both MS and general population.

, held April 13-18, in Denver, Colorado, by lead author 

As of July 12, 2023, investigators received data on 3253 cumulative MS pregnancies from the Roche safety database (prospectively, n = 2446; retrospectively, n = 800; unspecified, n = 7). Among the prospective pregnancies, 855 (35.0%) had 

 exposure and 1016 (41.5%) had unknown exposure. Of 855 prospective pregnancies exposed 

, 512 had known outcomes including 431 (84.2%) live births, 4 (0.8%) ectopic pregnancies, 38 (7.4%) elective terminations, 38 (7.4%) spontaneous abortion, and 1 (0.2%) stillbirth.

Bove, associate professor of neurology at University of California, San Francisco, sat down with 

® at the meeting to further discuss the findings related to pregnancy outcomes in women exposed to ocrelizumab. She also spoke about the areas that may require further data collection and monitoring, especially concerning infant outcomes. Additionally, Bove talked about some recommendations that are suggested for healthcare professionals based on the study’s results.

REFERENCES
1. Bove R, Pietrasanta C, Oreja-Guevara C, et al. Pregnancy and Infant Outcomes in Females Receiving Ocrelizumab for the Treatment of Multiple Sclerosis: Analysis of over 3,000 Pregnancies to Date. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.

The associate professor of neurology at University of California, San Francisco talked about findings from an analysis that assessed the safety of ocrelizumab when administered close to pregnancy. [WATCH TIME: 5 minutes]

Bruce Bebo, PhD, talked about the Dystel Prize which is presented at AAN to a recognized individual who promotes further advancements in understanding MS.

Recognizing Excellence in MS Research, the Dystel Prize: Bruce Bebo, PhD

"Prizes like the Dystel Prize help elevate and recognize excellence in MS research and create excitement and interest, promoting MS as a specialty that deserves to be studied and investigated."

, director of the Multiple Sclerosis Program at University of California, Los Angeles (UCLA), received the 2024 John Dystel Prize for Multiple Sclerosis Research. Voskuhl delivered the Dystel Prize lecture and received the award presented at the 

The award recognized Voskuhl, also a professor of neurology at UCLA, in her research to understand the mechanisms underlying sex differences in MS and advance women’s health.

Voskuhl has performed extensive research to understand why women are more susceptible to develop MS than men. In her research, she made discoveries related to the influence of sex hormones and sex chromosomes in laboratory models, and then translated those results to the clinic. She conducted 4 clinical trials that assessed the effect of treatment of patients with MS with sex hormones. Voskuhl’s research reported a gene on women sex chromosomes that promoted inflammation. In addition, she investigated the brain-protective effects of the sex hormone estrogen and other estrogen receptor molecules that bind to estrogen docking sites.

, executive vice president of research at 

 and who presented the prize to Voskuhl, sat down with 

 at the meeting to talk more about the Dystel Prize and how it plays a role in advancing MS research. He also spoke about how the nomination process for the Dystel Prize works if clinicians were interested in nominating their colleagues. Additionally, Bebo discussed the reason why it is important to recognize and honor outstanding research in MS.

REFERENCES
1. Noted UCLA Neurologist Dr. Rhonda Voskuhl Wins 2024 John Dystel Prize for Multiple Sclerosis Research. News Release. National MS Society. Published April 2, 2024. Accessed April 15, 2024. https://www.nationalmssociety.org/About-the-Society/News/Noted-UCLA-Neurologist-Dr-Rhonda-Voskuhl-Wins-2024

discuss strategies for personalizing decisions and mitigating risks when stopping medication.

When to Stop Multiple Sclerosis Therapy

This is a video synopsis/summary of a panel discussion involving Ahmed Obeidat, MD, PhD; Riley Bove, MD; Stephen Krieger, MD; and Erin Longbrake, MD, PhD.

When considering discontinuing therapy for patients with stable multiple sclerosis (MS) who show no signs of inflammatory activity, the decision-making process is typically a shared 1 with the patient. One often considers stopping medication for older patients who have been stable for many years without new lesions, relapses, or enhancing lesions.

However, patients are generally hesitant to change their stable treatment regimens. Situations where therapy might be stopped often arise when additional risks, like infections, become apparent. In such cases, adjusting the treatment or discussing discontinuation with the patient may be considered.

The decision to stop medication is complex and relies heavily on shared decision-making and clinical experience due to the lack of definitive data to guide the decision. Regular monitoring is crucial to assess the evolving risk-benefit ratio.

There's also a challenge in determining whether the absence of relapses is due to the patient's biology or the effectiveness of the medication. This uncertainty underscores the importance of continued vigilance and monitoring, especially when considering discontinuing B-cell depleting therapies.

Cell-depleting immunotherapies are believed to have longer-lasting effects, providing some reassurance when considering discontinuation. However, vigilant monitoring remains essential, especially as B-cells come back online after discontinuation, to understand their activity and potential impact on the patient's condition.

Video synopsis is AI-generated and reviewed by NeurologyLive editorial staff.

Ahmed Obeidat, MD, PhD, Erin Longbrake, MD, PhD, Stephen Krieger, MD, and Riley Bove, MD, discuss strategies for personalizing decisions and mitigating risks when stopping medication.

discuss the definition of high-efficacy therapy and its place in MS care.

Customizing Treatment Approaches With High Efficacy Therapies

The conversation revolves around the classification and efficacy of medications used in the treatment of multiple sclerosis (MS). The participants discuss 2 ongoing pragmatic trials: TREAT-MS and DELIVER-MS, which aim to compare different treatment approaches through randomization.

One participant shares their perspective on these trials, emphasizing the importance of objective evidence to support the early aggressive treatment approach in MS. They believe that starting treatment early with more effective therapies can lead to better outcomes, as delaying treatment can result in long-term complications.

In terms of medication efficacy, the participant categorizes medications into high, medium, and traditional efficacy tiers. High-efficacy medications include anti-CD20 therapy, S1P receptor modulators, and cladribine. On the other hand, first-line self-injectable therapies like interferons and glatiramer acetate are considered to be on the lower end of efficacy.

The efficacy of teriflunomide, an oral medication, remains ambiguous. While it was initially considered modestly effective compared to older injectable interferons, recent trial data suggests varying efficacy levels when compared to newer medications like ocrelizumab, ublituximab, and evobrutinib.

There is uncertainty regarding where to place teriflunomide in the current spectrum of MS treatments. Despite its inconsistent efficacy in trials against newer agents, it remains a viable treatment option with potential benefits.

The participants also discuss whether clinical trials are designed to favor teriflunomide. One participant suggests that trials are not intentionally designed to make teriflunomide appear more effective but acknowledges the challenges in determining its exact place in MS treatment protocols.

Ahmed Obeidat, MD, PhD, Riley Bove, MD, Stephen Krieger, MD, and Erin Longbrake, MD, PhD, discuss the definition of high-efficacy therapy and its place in MS care.

Thomas F. Scott, MD, discussed exploring the potential role of BTK inhibitors and advanced MRI techniques to address smoldering multiple sclerosis.

"We need to look at more nontraditional measures if we want to delve into the subject of smoldering [multiple sclerosis] and evaluate the potential role of [Bruton tyrosine kinase] inhibitors."

In the field of multiple sclerosis (MS), disability caused by the disease can derive from acute relapses or because of slow and steady deterioration. In the last decades, researchers have developed effective therapies to control the relapse activity in MS. These agents were primarily aimed to systemically target the peripheral immune system and/or prevent central nervous system (CNS) infiltration of immune cells.

One promising approach that may address the unmet need in patients may be inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of B cells as well as myeloid cells.

In a recent analysis of phase 2 studies assessing fenebrutinib (Roche), an oral investigational BTK inhibitor, results showed that the safety profile of the agent was similar in both patients with relapsing MS and other previously studied autoimmune indications. Presented at the 

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