Expert clinicians offer their perspectives on transitional care in pediatric MS, a biomarker for SUDEP, and a novel approach to narcolepsy, among other topics.
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 a conversation on the use of focused ultrasound to open the blood-brain barrier for Alzheimer disease therapy with Ali Rezai, MD; the potential of MCHR1 antagonists in the treatment of narcolepsy with Thomas Scammell, MD; preparing teens with multiple sclerosis for the transition to adult care with Vikram Bhise, MD; the findings of the NAVIGATE-ESUS trial in stroke with Alexander Merkler, MD, MS; and the possibility of short-term heart rate variability as a biomarker for sudden unexplained death in epilepsy with Orrin Devinsky, MD.
Click through the slides to see and read more from each expert’s exclusive conversation with NeurologyLive® in November 2021.
WATCH TIME: 3 minutes
“This is actually a new mechanism for clinicians to learn about—I think many doctors who are familiar with the treatment of narcolepsy know about the conventional medications, but this is a novel signaling molecule, and there may be many novel benefits, but there could also be some novel concerns. So, we really need to work towards thoroughly studying the safety and efficacy of this medication as it comes through the pipeline.”
Harmony Biosciences recently acquired HBS-102 (formerly CSTI-100; ConSynance Therapeutics), a melanin-concentrating hormone receptor 1 (MCHR1) antagonist with the potential for a novel approach to the treatment of narcolepsy, particularly symptoms of rapid eye movement (REM) sleep dysregulation—cataplexy, hallucinations, and sleep paralysis.1 Following the acquisition, Thomas Scammell, MD, professor of neurology, Beth Israel Deaconess Medical Center, spoke with NeurologyLive® on the potential of MCHR1 antagonists.
Scammell noted that the mechanism has yet to be tested in humans, with him and his team investigating a separate compound, SNAP 94847, in an orexin knockout mouse model of narcolepsy, seeing a significant reduction in cataplexy events.2 Harmony is currently putting forth efforts to initiate a phase 2 clinical trial of HBS-102 once an investigational new drug application is open.
WATCH TIME: 5 minutes
“A lot of it—and I don't have a defined point [but] hopefully, that's something we can figure out in further studies—is listening very carefully for that point where teenagers are ready to listen. There may be a sense in the beginning that it's just too overwhelming, or they know that their parents are taking care of it, or the perhaps they're in a bit of denial, or just that they want some time to process things.”
Transition readiness is crucial for patients with pediatric multiple sclerosis (MS), ideally discussed during a visit(s) focused solely on the move to adulthood. Vikram Bhise, MD, associate professor, pediatrics and neurology; and division director, division of child neurology and neurodevelopmental disabilities, Rutgers–Robert Wood Johnson Medical School, discussed the need to engage teenagers with MS in conversation, particularly when they signal that they are ready to begin learning more about their condition. Listening for this readiness can assist in identifying the best time to schedule a transition visit to set goals and identify patients’ individual areas of need.3
WATCH TIME: 4 minutes
"We did this exploratory analysis under the hypothesis that patients with left ventricular dysfunction may be at risk for recurrent stroke, and that anticoagulation may be beneficial to that patient group. Essentially, left ventricular dysfunction may be a novel stroke risk factor and perhaps anticoagulation can help them.”
The phase 3 NAVIGATE-ESUS trial (NCT02313909) was a comparator study that evaluated the effect of rivaroxaban (Xarelto; Janssen), an anticoagulant, with that of aspirin on reducing the risk of recurrent stroke or systemic embolism in those with embolic strokes of undetermined source (ESUS). Patients were randomized to either 15 mg of rivaroxaban or 100 mg of aspirin once daily.4
Led by Alexander Merkler, MD, MS, a post-hoc analysis specifically looked at those with left ventricular dysfunction. Over a median follow-up of 10.4 months, the primary outcome of recurrent stroke or systemic embolism occurred in 321 participants (4.9% per year). When comparing the 2 treatments, event rates were 2.4% per year (95% CI, 1.1-5.4) in those assigned to rivaroxaban versus 6.5% (95% CI, 4.0-11) in those on aspirin. In comparison, event rates were noticeably similar between treatment arms for those without LV dysfunction.
WATCH TIME: 4 minutes
"If only we could have a biomarker that says, ‘This looks like a well-controlled person who should be at low-risk but might actually be at high-risk based on their heart rate variability or other markers.’ The only biomarker that’s been proposed, has some support, and makes logical sense, is post ictal EEG suppression."
Sudden unexplained death in epilepsy (SUDEP) affects nearly 3000 individuals each year and remains among the most complicated events to tackle in epilepsy care. While there are no FDA-approved medications to treat SUDEP, clinicians have focused on controlling patient’s seizures to try to reduce the risk. In the largest SUDEP biomarker study conducted to date, senior author Orrin Devinsky, MD, and colleagues found an association between short-term heart rate variability and SUDEP.5
The study featured 31 SUDEP cases and 56 controls. Investigators found normalized low-frequency power (LFP) to be lower in SUDEP cases (median, 42.5 [interquartile range (IQR), 32.6-52.6]) than epilepsy controls (median, 55.5 [IQR, 40.7-68.9]; P = .015; critical value = 0.025). Additionally, there was a negative correlation between LFP and the latency to SUDEP, where each 1% incremental reduction in normalized LFP conferred a 2.7% (95% CI, 0.95-0.995) decrease in the latency to SUDEP (P = .017; critical value = .025).
WATCH TIME: 7 minutes
“The blood-brain barrier is a diffusion barrier, limiting the access of most substances from the blood vessels into the brain tissue, and essentially substances that are larger than 400 Dalton molecular weight do not cross the blood-brain barrier readily—this includes many pharmaceuticals, medications, antibodies, and other therapies. So, in the neurosciences, a big problem has been the noninvasive opening of the blood-brain barrier, and focused ultrasound allows that.”
The focal opening of the blood-brain barrier (BBB) in patients with mild Alzheimer disease (AD) using MRI-guided focused ultrasound (FUS) was found to be safe and effective, according to early findings from a multicenter clinical trial. Lead investigator Ali Rezai, MD, executive chair, Rockefeller Neuroscience Institute; vice president, neuroscience; and associate dean and John D. Rockefeller IV tenured professor in neuroscience, West Virginia University, spoke with NeurologyLive® to provide an overview of the FUS technology, as well as processes for opening the BBB.
Emerging FUS technology is a noninvasive, outpatient procedure, allowing clinicians to use MRI to target different areas of the brain with precision. Rezai outlined 3 different applications of the treatment, including 1 that is FDA-approved and reimbursed by Medicare for the treatment of Parkinson disease and essential tremor.
To hear more insight from experts in the clinical care of patients and leading researchers in neurology, check out more of NeurologyLive®'s videos.