Post-AAN Perspectives: Recapping Major Areas of Growth in Neurology

Robert Bermel, MD; Dileep Nair, MD; Andrew Russman, DO

The American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, is considered a premier event in the field of neurology, drawing thousands of neurologists, neuroscientists, and healthcare professionals from around the world. The conference serves as a platform for the dissemination of cutting-edge research, innovative clinical practices, and emerging trends in neurology.

Several of the presentations at this meeting often set the stage for future advancements in neurology and patient care. This year’s event was among the largest it’s ever been, fostering networking and collaboration among professionals, offering numerous opportunities for attendees to connect with peers, share insights, and discuss challenges and solutions in the field.

Weeks after the conclusion of AAN 2024, NeurologyLive® sat down with a trio of experts from Cleveland Clinic who provided unique perspectives on the advances in their respective fields, highlighting some of the notable research and discussion from the meeting. Specifically, Dileep Nair, MD, an epilepsy neurologist and head of the adult section in epilepsy at the Epilepsy Center, provided insight on the epilepsy-focused side of the meeting, whereas Andrew Russman, DO, head of the Stroke Program and medical director of the Comprehensive Stroke Center, gave the stroke side of the meeting. Robert Bermel, MD, director of the Mellen Center for MS, rounded out the group, giving the latest on advances in multiple sclerosis (MS).

Dileep Nair, MD

Dileep Nair, MD, on Epilepsy:

One of the main themes that played out at AAN relating to epilepsy is the evolution of some of the newer therapies that are coming now for epilepsy. These include some gene therapy techniques, as well as the expanding role of neuromodulation in epilepsy and the under appreciation or the underutilization of epilepsy surgery as a methodology. These were some of the main themes. There's also this question about burden and recognition of epilepsy as an entity early in the disease course. There's some concern about delay in diagnosis that was brought up by some of the research presented.

The most important thing I would highlight is the expanding role of therapy and hope for patients in whom drug-resistant epilepsy is still a lifelong burden for them at this moment in time. There is expanding roles of new therapies and new types of medications that will hopefully diminish the burden of epilepsy in those patients. There's a theme of hope through the research presented that in the future, our methods of how we care for epilepsy may change fundamentally.

The other is that there is an expanding understanding of the morbidity associated with poorly treated epilepsy. These are two things I think the general neurology community should be more in tune with. In particular, there were some aspects of recognizing epilepsy early in the disease course that may be important. One of the press releases that came out of the AAN was related to a study by Jacqueline French, MD. This study was on the early diagnosis of epilepsy, based on the recognition that non-motor symptoms are often the very first symptoms that some young patients with epilepsy exhibit. And unfortunately, the first seizure may only be recognized years later when they begin to have their motor seizures. The non-motor symptoms include things like auras, nausea, visual distortions, etc. But they can also include brief episodes where they have an arrest of behavior or changes to their cognition that if the history is obtained, may indicate that the patient is having seizures, rather than waiting years before the disease progresses, making it more likely to lead to a more complicated epilepsy course, with a late diagnosis.

Another notable aspect from AAN was in one of the platform prep presentations, where they showed that there is a disparity problem in epilepsy surgery, and in particular, when it relates to the timing of when epilepsy surgery is first recommended to a patient. It showed that this recommendation is dependent upon things like insurance, race, and income status. These disparities that exist currently in the delivery of epilepsy surgery might explain a little bit the underutilization of epilepsy surgery. Again, we need to be more cognizant of how we deal with patients who are in these vulnerable population groups.

The ultimate morbidity with epilepsy is something called sudden unexplained death in epilepsy, or SUDEP. Some of the research that was presented at AAN suggests that there may be biomarkers that we can look at in the heart and in the EKG rhythms beforehand. In a small group of patients who eventually suffered SUDEP, investigators looked at their EKGs in the Epilepsy Monitoring Unit and found some subtle changes in the QT interval as well as the heart rate variability that might help us understand a little bit more who is at risk for a SUDEP. Maybe through these measures, it will allow us to focus on these at-risk patients in terms of reducing their seizures with some of the therapies available.

Andrew Russman, DO

Andrew Russman, DO, on Stroke:

The AAN provides an opportunity for the stroke community to network. While its presentations may not be as groundbreaking as those at larger stroke meetings, there were still notable highlights, indicating the field's direction.

We're seeing greater trends toward identifying opportunities for catheter-based procedures to try and help patients with strokes of different types. At other meetings, we’ve seen a lot of presentations about middle meningeal artery embolization for patients who have subdural hemorrhage. While that particular condition was not a big theme at the AAN, one of the presentations that I was impressed with was an endovascular technique in order to provide CSF shunting for patients with hydrocephalus after subarachnoid hemorrhage. Currently, endovascular techniques or endoscopic techniques or have not reached the recommended mainstream for patients with subarachnoid hemorrhage. External ventricular drains are sort of the mainstay of therapy for patients with hydrocephalus with subarachnoid hemorrhage; however, this shunting system that was developed for endovascular use seems feasible. I'd be excited to see what further work is done to show how it compares to some of our traditional techniques, especially external ventricular drains. If it were comparable, maybe easier to perform with less risk for patients, I certainly see the opportunities there, but we don't know that information yet.

Some of the other things that I thought were interesting were a few presentations on AI. AI has sort of penetrated the use of a variety of applications that we have to detect large blood vessel occlusions in patients who present to the emergency department where we're looking at CT angiography in particular. When you use these types of tools, you're quicker to identify large vessel occlusions, you get them to the angio suite quicker. Time to treatment is a proxy for a potential outcome, so I do think that earlier treatment of patients, and the expansion of various AI techniques to identify candidates for procedural interventions is something we're going to continue to see grow, especially when we start to look at more distal vessels, or what we call mini medium vessel occlusions, the stroke is occurring in the more distal portion of the middle cerebral or M2 vessels. Those patients are not traditional targets for thrombectomy, but there are possible interventions and devices now available to intervene on them. In order to detect those, you need more tools. That’s where AI is going to be helpful to identify some of those more distal occlusions.

We continue to see some publications on patients with mild acute stroke deficits, people with lower NIH Stroke Scale scores, and we've seen a few studies over the years looking at patients who had nondisabling stroke symptoms within the 5 range on NIH Stroke Scale. We're often reviewing these cases to look for opportunities for how we can help patients. Traditionally, there was a concern that those patients are at higher risk of neurologic deterioration, as we do see rates upwards of 30% that patients may neurologically worsen in the 72 hours after their initial acute stroke presentation.

One of the meta analyses that I saw at AAN pointed out how, if you compare giving antiplatelets versus thrombolytic to these mild stroke patients, they clearly don’t do better with thrombolytic therapy. Yet, I don't think this signals that every patient in that group would has potentially of not benefiting. Not every patient with NIH (Stroke Scale score) less than 5 is created equal. Patients can have quite disabling symptoms with lower end stroke scales. For instance, aphasias or visual loss can be life changing events for patients, which is different than patients with mild facial weakness or sensory changes. Again, not every NIH less than 5 is created equal. We still need to consider those patients with disabling deficits, an offer them thrombolysis when they meet the criteria, and continue to explore that population.

When we look at our patient populations—I did see a poster looking at patients who are under treated or untreated for post stroke depression—it seems as though those with higher poverty index scores are really slipping through the gaps more often. We need to design interventions to look at that disparity in care. We don't know whether or not the under treatment is driven by patient specific factors or driven by the systematic issues, insurance coverages and other factors. But we need to be sensitive as clinicians to the risk of those in vulnerable populations, including those higher on the poverty scale who are going to suffer from under treatment, and to look at whether or not there are resources we can offer or ways we can connect them.

Another aspect of AAN that I thought was very interesting was that many clinicians are familiar with the fact that in patients with systemic lupus erythematosus, the use of hydroxychloroquine is sort of standard therapy for many patients in that population. We often find that many patients are not on this therapy or discontinue the therapy. There are potential long term risks, ophthalmologic risks, among others, to being on long term hydroxychloroquine. But one of the benefits showed that when you look at populations of patients who are on hydroxychloroquine, compared to those that are not, you find less small vessel disease, or cerebral microangiopathy. This signals some type of putative effect from that medication that I don't think can be ignored. We do see a lot of this kind of white matter disease develop in patients with lupus, and I think that could be a downstream cause of vascular dementia and other conditions. We should really be aware of this issue and make sure that patients are appropriately being treated for the prevention of this condition.

Robert Bermel, MD

Robert Bermel, MD, on Multiple Sclerosis:

I think we're in a transition period in the MS field where everyone feels comfortable with the existing high-efficacy therapies, including B-cell depleting therapy, the number of S1P receptor modulators on the market, and the fumarates. However, there's a desire to move into a new zone to potentially help patients with progressive MS.

We saw a combination of data on existing therapies. One of the most exciting things was the 10-year follow-up data on the ocrelizumab trials for both relapsing-remitting MS and progressive MS. This data is reassuring, showing that patients who started B-cell depleting therapy with ocrelizumab early do very well over the long term. For instance, over 90% of the patients followed up for 10 years didn't need a walking aid, and over three-quarters of those who started on ocrelizumab early did not have any disability progression. These long-term efficacy results with ocrelizumab are encouraging, especially since many patients are now on B-cell depleting therapy.

At the same session where the long-term efficacy for ocrelizumab was presented, we also heard about extended interval dosing of biosimilar rituximab. This strategy uses B-cell depleting therapy in a different way, potentially optimizing high-efficacy therapy for lower cost and higher safety, even though it currently lacks regulatory approval.

We also have newer generations of therapy, like subcutaneous administration of ocrelizumab, which can be accomplished in about 10 minutes. This method is equally effective as IV administration and may expand access to B-cell therapies for those who do not live near an infusion center or cannot easily access infusible therapy.

There's a strong desire to see data on new mechanisms of action. For example, we saw interest in BTK inhibitors at the poster sessions at AAN. I presented data on oral BTK inhibitors from other disease states like chronic spontaneous urticaria, providing safety data, especially around immunoglobulin levels. People are waiting for definitive safety data on BTK inhibitors, such as liver toxicity and liver function test abnormalities, and efficacy data, especially after the evobrutinib efficacy data showed equivalence with teriflunomide.

Overall, there's hope that another mechanism of action like BTK could provide new options for patients with MS, particularly for those with progressive MS. Any treatment that offers access to new mechanisms of action will be welcomed.

Transcript edited for clarity.