NeurologyLive® Top Expert Interviews: January 2022

The NeurologyLive^® team has been as busy as always bringing you the latest clinical news and research updates in neurology over the last month, including conducting several interviews with experts across a number of different and varying topics.

Among these included conversations about the challenges in conducting clinical trials in migraine with Christina Szperka, MD, MSCE; the use of MR fingerprinting in epilepsy care with Irene Wang, PhD; the current understanding of disorders of consciousness and COVID-19 with David Fischer, MD; the development of the SAGE test for early dementia detection with Douglas Scharre, MD; addressing disparities in the US following COVID-19 with Mitzi Joi Williams, MD; and the current monoclonal antibodies in development for Alzheimer disease with Anton Porsteinsson, MD.

Click through the slides to see and read more from each expert’s exclusive conversation with NeurologyLive^® in January 2022.

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WATCH TIME: 6 minutes

Conducting Clinical Trials in Pediatric Migraine: Christina Szperka, MD, MSCE

“The CHAMP study showed that there were a lot of adverse effects in those meds, particularly topiramate. So, if we have another therapy that does ultimately have long-term safety and fewer adverse effects and that's easier in terms of adherence, maybe then the prescription patterns will eventually shift. But for right now, early on, when they meds have only been approved in adults for a couple of years, it's hard sometimes for parents to say, ‘I want to put my child in that study.’ That's something that we wrestle with, and it just depends.”

Difficulties surround enrollment for clinical trials in pediatric migraine, as new medications often have no long-term safety data, complicating parents’ decisions when it comes to enrolling their children and expose them to potential risks of an unproven therapy. Christina Szperka, MD, MSCE, director of the Pediatric Headache Program at the Children’s Hospital of Philadelphia (CHOP), commented on this issue, adding that trials are often designed for patients with “regular, more straightforward, earlier-on migraine,” leaving out those who have continuous headache and have become ineligible after failing multiple therapies.

In conversation with NeurologyLive^®, Szperka also discussed advances made for general migraine during the COVID-19 pandemic, including a paper she coauthored during the lockdown period entitled, “Migraine care in the era of COVID-19: Clinical pearls and plea to insurers,” which provided alternative options for patients with migraine, in the event they could not visit a facility for usual procedures.¹

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WATCH TIME: 3 minutes

Utilizing MR Fingerprinting to Benefit Epilepsy Care: Irene Wang, PhD

"What we do currently with MRI is look at dark or bright. This is similar to feeling a high or low fever. But what we need to do is have that number that could tell us about the state of the brain—the healthy state of the brain, so to speak."

MR fingerprinting is a relatively recent approach to the acquisition and evaluation of MRI data aimed at generating quantitative multiparametric data from a single acquisition. The idea behind MR fingerprinting is that it will make comparison across individuals, scanners, and vendors possible, rather than the current situation in which most imaging data is qualitative. The benefits of MR fingerprinting were further showcased at the recently concluded 2021 American Epilepsy Society (AES) Annual Meeting, December 3-7, in Chicago, Illinois, with research conducted by Irene Wang, PhD.

Wang, the research director and a staff scientist at the Comprehensive Epilepsy Center of Cleveland Clinic, presented 3 abstracts that evaluated MR fingerprinting in the characterization of medically intractable focal epilepsy and focal cortical dysplasia (FCD). FCD, one of the most common pathologies for medically intractable focal epilepsy, can be difficult to detect by using traditional weighted MRI. Using a radiomics extraction approach, the data showed high accuracies of MR fingerprinting to classify FCD from healthy tissue, and to classify FCD type 2 from type 1.²

These projects have been in the works for years, according to Wang. She sat down with NeurologyLive^® to discuss the reasoning behind the research, how this novel approach will change the way epilepsy is viewed, and why clinicians should be excited about it.

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WATCH TIME: 3 minutes

Disorders of Consciousness and COVID-19: David Fischer, MD

“Medical teams and families wanted to know if life-sustaining treatment should be continued or not, basically asking how long they could expect these disorders of consciousness to continue, and we really didn’t know. We didn’t really know how COVID was affecting the brain.”

A recent prospective study investigated patients with COVID-19 and disorders of consciousness (COVID-DoC), which has been identified as a serious complication of the virus. As prognosis and pathophysiology of the condition are not yet fully understood, an added layer or complications arose in terms of the decision to continue life-sustaining treatment.

Led by David Fischer, MD, neurocritical care fellow at Massachusetts General Hospital and Brigham and Women’s Hospital, investigators enrolled 12 patients with COVID-DoC, 11 of whom recovered consciousness after 0-25 days (median, 7 [5-14.5]) after stopping continuous intravenous sedation—excluding 1 patient who died following enrollment. We sat down with Fischer to learn more about study findings, the most surprising of which was the recovery of significant neurologic function and minimal disability by 9 surviving patients upon returning home.³

Speaking with NeurologyLive^®, Fischer outlined motivations for the study, which was prompted by questions from families and medical teams regarding admitted patients with severe COVID-19 infections and DoC that were not waking up. This generated issues for clinicians, Fischer said, as they were unable to provide informed advice to families and medical teams regarding the withdrawal of life-sustaining treatment.

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WATCH TIME: 2 minutes

Development of SAGE for Early Dementia Detection: Douglas Scharre, MD

“The reason I developed and invented this test was because, as a neurologist, seeing cognitively impaired patients and/or with memory disorders, the number of individuals that would come into our clinic that had had issues for 3-4 years by the time they actually came to see us. It was clear to me that patients weren't right on top of it all the time, and primary care doctors weren't always referring.”

Detecting signs of dementia early can have a crucial impact on patients’ outcomes, allowing for health care providers to intervene with resources and treatment, if necessary. Several tests have emerged to identify signs of mild cognitive impairment (MCI), with the Self-Administered Gerocognitive Examination (SAGE) recently showing success in a longitudinal study of its efficacy compared to the Mini-Mental State Examination (MMSE).⁴

Douglas Scharre, MD, director, Division of Cognitive and Memory Disorders, department of neurology, the Ohio State Wexner Medical Center, sat down with NeurologyLive^® to discuss SAGE, which is a pen-and-paper assessment, and its digital companion assessment, BrainTest, which can be performed on a tablet or touchscreen computer. According to Scharre, he was prompted to develop SAGE and BrainTest upon recognizing that patients had cognitive issues that had persisted for several years and had not sought treatment, therefore creating a delay in their identification and treatment. 

Also discussed were findings from the study, where investigators concluded that SAGE identified MCI conversion to dementia at least 6 months ahead of the MMSE, which is not self-administered. The patients that were identified as being likely to eventually develop dementia had a 2- to 3-point decline in SAGE scores 12-18 months from baseline, which was a significant decline, Scharre said.

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WATCH TIME: 3 minutes

Addressing Health Disparities in the US Following COVID-19: Mitzi Joi Williams, MD

“Since the advent of the COVID-19 pandemic, I think it's really shined a spotlight on the health disparities in our country. We've learned a lot more about how ethnicity, systemic racism, how living in rural populations, and having limited access to transportation and care has really affected health outcomes in a real time basis.”

In the field of multiple sclerosis (MS), as with other conditions, health disparities persist, with barriers to care negatively affecting certain populations. Amidst the COVID-19 pandemic, these issues have come to the surface in MS, highlighting the need to put forth fresh initiatives to better serve these patients.

To learn more about shifts in care for underrepresented and minority populations in 2021, we sat down with Mitzi Joi Williams, MD, board certified neurologist and MS specialist, and founder and CEO, Joi Life Wellness Group Multiple Sclerosis Center. In conversation with NeurologyLive^®, Williams highlighted endeavors originating during the pandemic, including the establishment of the first trial of its kind to focus on how ocrelizumab (Ocrevus; Genentech) affects minority populations—the CHIMES trial (NCT04377555)—and the launch of the National African Americans with MS Registry.

Also discussed were the pros and cons of telemedicine for minority patients with MS. Williams described the practice as a “double-edged sword,” noting that telemedicine increases access and assists those who may not have had reliable transportation to and from appointments but may have negatively impacted those who do not have access to the internet or lack technological proficiency.

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WATCH TIME: 9 minutes

Monoclonal Antibodies in Development for Alzheimer Disease: Anton Porsteinsson, MD

“In my book, what’s happening with the other humanized monoclonal antibodies that target fibrillary and, to some degree, soluble beta-amyloid—that’s a very intriguing story. It goes beyond aducanumab.”

Last year, the field of Alzheimer disease (AD) underwent a massive change, headlined by the FDA approval of the first therapy for the disease since 2003: aducanumab (Aduhelm; Biogen). Although, despite the controversial conversations happening around the approval of the antiamyloid monoclonal antibody, far more was happening in the background.

For Anton Porsteinsson, MD, director, Alzheimer's Disease Care, Research and Education Program; William B. and Sheila Konar Professor of Psychiatry, School of Medicine and Dentistry, University of Rochester, the bustling activity of the pipeline is a sign of health for the field. In a conversation with NeurologyLive^®, he highlighted some of the progress that has been made by additional antiamyloid-ß antibodies in the pipeline and offered his insight into how their advancement will lend a better idea of the effectiveness of the overall class of medicines.

Porsteinsson focused on the 3 main players that are making their way through phase 3 trials—namely lecanemab (Eisai/Biogen), donanemab (Eli Lilly), and gantenerumab (Roche)—and provided context on the current understanding of their effect on AD and the structure of their clinical trials. All 3 agents have been fast tracked for review by the FDA, and a few of them are expected to attempt the same route of accelerated approval that aducanumab did.

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REFERENCES
1. Szperka CL, Ailani J, Barmherzig R, et al. Migraine care in the era of COVID-19: Clinical pearls and plea to insurers. Headache. 2020;60(5):833-842. doi:10.1111/head.13810
2. Choi JY, Su T, Hu S, et al. MR Fingerprinting radiomics for characterization of focal cortical dysaplasia. Presented at AES Annual Meeting; December 3-7, 2021. Poster 3.235
3. Fischer D, Snider SB, Barra ME, et al. Disorders of consciousness associated with COVID-19: A prospective, multimodal study of recovery and brain connectivity. Neurology. Published online December 3, 2021. doi:10.1212/WNL.0000000000013067
4. Scharre DW, Chang S, Nagaraja HN, Wheeler NC, Kataki M. Self-Administered Gerocognitive Examination: longitudinal cohort testing for the early detection of dementia conversion. Alzheimers Res Ther. 2021;13(1):192. doi:10.1186/s13195-021-00930-4