Next Steps in Improving Autoimmune Encephalitis Care

Divyanshu Dubey, MBBS

This is the second of a 2-part interview. To view part 1, click here.

Autoimmune encephalitis is the collection of related conditions in which the body’s immune system attacks the brain, causing inflammation. Like multiple sclerosis (MS), the disease can be progressive or relapsing-remitting, with alternating flare-ups and periods of recovery. It has many subtypes that are dependent on the antibodies present which mistakenly attack brain cells.

At the ACTRIMS Forum 2021, February 25–27, Divyanshu Dubey, MBBS, gave an invited talk on autoimmune encephalitis, claiming that the incidence of the disease is growing in part due to the increased recognition and discovery of additional neural specific antibodies. In his presentation, he also noted that understanding the diagnostic potential and limitations of autoantibody detection assays may aid clinicians in optimal utilization of available autoimmune panels.

Dubey, an assistant professor of neurology at Mayo Clinic, sat down to discuss the next steps in improving autoimmune encephalitis care. In the second half of this interview, he detailed research that needs more attention, value in autoantibody assays, and the topics from ACTRIMS Forum 2021 that encompass the autoimmune encephalitis and COVID-19.

NeurologyLive: Are there areas or aspects that you feel need more research or you feel are kind of the next steps in research in this area?

Divyanshu Dubey, MBBS: Despite the significant growth that has happened, I still feel about close to 40% to 50% of all autoimmune encephalitis cases continue to be zero negative, suggesting they don’t really have a biomarker. In these cases, the number of these antibodies are high, and these specific antibodies are likely to continue to increase over time. Secondly, we’re realizing the limitations of some of these antibodies. Refining the clinical utility and improving the tests which are utilized for detection of these antibodies needs to be done. That’s another area of research which will continue.

Moving on from the diagnosis, a lot of work needs to be done on treatment of these conditions. We are still utilizing some of the methods, treatment protocols, and treatment medications which have been there for many years. Many of the new medications are monoclonal antibodies, which will be utilized in the future management of these conditions. That work still needs to be done and is actively going on.

Lastly, the one question I’m faced with every week when I see some of these patients is in terms of prognostication. That includes how long to treat these patients, which patients are going to monophasic versus which are going to continue to have relapses. We sort of understand that natural history, that long-term course, is something we’re still learning about and are actively investigating. Again, that’s another area which a lot of work will be done in the future.

How can understanding about the diagnostic potential of autoantibody assays aid clinicians in clinical care?

Half of my time I work in the neuroimmunology lab and the remaining 50% I see patients. Our lab gets about 200,000 samples every year for testing of these antibodies. We recognize that ultimately, we’re not treating antibodies, but we’ll keep treating patients. Understanding how to interpret these antibodies is extremely crucial. What do titers mean in certain scenarios? For example, GAD65 antibodies are where low titers can be found in normal human beings or can be associated with non-neurological autoimmunity. What samples do we test? Whether its serum versus CSF. Which antibodies is CSF highly specific or sensitive to compared to which one’s serums are better? When to test these antibodies before instituting treatments, such as plasma exchange. What tests are being utilized, and what are the limitations of the diagnostic assays? As these antibodies become a common practice in neurology, both inpatient and outpatient neurology, these are the things which even clinicians who are not actively involved in research of autoimmune encephalitis or autoimmune neurological conditions, will have to get some understanding. That includes the interpretations as well as the limitations. That’s something I will be talking about briefly in my talk as well.

With this being the first major MS-focused meeting of 2021, what is your main takeaway about the state of science and research in autoimmune encephalitis and MS amid the COVID pandemic based on the data and conversations happening at the ACTRIMS Forum?

I think I’m going to look forward to a lot of the research that’s going to be discussed at this meeting because COVID-19 has forced conferences to be canceled or delayed. This will be sort of hoarding up a lot of research that has been built up over the last few months or year or so. I’m looking forward to discussions with my colleagues who work in this area and getting updates from them in terms of what new things have been discovered in this field. This is an actively evolving field; nearly every year a new biomarker is discovered.

I also want to understand more about what impact COVID-19 has had. We’ve come across many studies which have suggested that COVID-19 can trigger autoimmunity, even though there is not clear-cut data to support this right now. We have seen certain associations where patients who develop COVID-19 first go on to develop certain antibodies and encephalitis either a few weeks or 2 months later. That is a question which is still being asked and many people are trying to answer it using techniques such as antibody detection or cytokine chemokine. That’s an area that would be interesting to see if there’s more literature or research to shed light on that.

One question we’re all facing in our clinic is the impact of these immunosuppressive drugs on COVID-19 vaccination. This is a discussion I have with my patients nearly every week, because many of them have very suppressed immune systems because of medications such as rituximab or cyclophosphamide. That is something which, hopefully in the future, we’ll be able to understand. How these medications will end up affecting the efficacy of the vaccine when it becomes available to these patients? Also, would there be strategies where we can somehow enhance their response by taking certain strategies so that these patients are also protected from infection?

Transcript edited for clarity.