All right, thanks to everyone for coming out and spending the evening with us. It's truly a privilege to get to share this space and learn from my colleagues here, and we're hearing from lots of disciplines caring for patients in a comprehensive way, patients who are living with epilepsy. Well, when it comes to mental health care for patients who are living with epilepsy, that in itself is quite a multidisciplinary enterprise. Not just a neuropsychiatrist, but we're thinking about psychologists, we're thinking about licensed clinical social workers, advanced practice providers, and many, many others. I have no financial disclosures. These are our learning goals that we hope each of you is able to take away from your time with us, and a bit of a roadmap for this part of the symposium. We're gonna be thinking, how do we conceptualize neuropsychiatric symptoms in epilepsy, thinking about their phenomenology, their multifactorial etiologies, and how all of those interact in a biopsychosocial way? How do I sit with a patient and assess for neuropsychiatric comorbidities, the questions and things that I would be weighing on my mind in those interviews? And then a particular focus on the neuropsychiatry of epilepsy surgery. So in 2014, the International League Against Epilepsy, it took a really important step, which is to recognize that epilepsy is not just about clinical seizures. No, it's far more than that. It is about the impact on an individual's neurobiological, psychological, and sociocultural domains, and how that influences the overall quality of a patient's life, their functioning, the story that they would tell of themselves. One of my favorite neuropsychiatrists, Michael Trimble in the UK, has done a lot of really incredible work in epilepsy, and he wrote a prolific history of neuropsychiatry called The Intentional Brain. And one of the quotations from that, I think, captures the essence of what the ILAE was doing as well. Epilepsy is not just about seizures, it's a diagnosis of continuous cerebral electrochemical activity in the brain that every now and then will have intermittent eruptions that reaches the threshold of a clinical seizure. And if the first question that a treating clinician asks is how many seizures have you had, then I think that clinician needs to revisit their understanding of the disorder. So as a neuropsychiatrist talking to you about epilepsy, I would be remiss if I did not include at least one quotation from Hippocrates. And I bet everybody in here already has an idea about what one it's gonna be. But Hippocrates wrote on the sacred disease and did incredibly important work to shift our understanding away from divine intervention to the organ of the brain as where epilepsy is seated. And in all of his prescient work, he said that melancholics ordinarily become epileptics and epileptics melancholics. So what did he mean by that? Well, we know from epidemiologic data that patients living with epilepsy have higher comorbidity rates of psychopathology across psychiatric symptoms from mood disorders and anxiety disorders, psychotic disorders. ADHD can be diagnosed in roughly a third of children at the time of a seizure onset. And suicidality, 25%, suicidality capturing the whole spectrum of suicidal behaviors from ideation to attempts and completions. And a study that's a bit dated now, but about 20 years ago found that 12% of patients living with epilepsy died by suicide compared to just over 1% in the general population at that time. That's a number that I think causes all of us to see how imperative it is to have mental health care integrated into epilepsy care. They're inseparable. So that bi-directional relationship, if you take patients who have a diagnosis of what would be considered a primary psychiatric disorder, major depression, bipolar disorder, anxiety disorders, or a prior suicide attempt, and they've never had a seizure in their entire life, and you follow them throughout several years, you find that the odds of them having epilepsy later in life is between two to three times. So Hippocrates did not have the epidemiologic methodologies that we do today, but he predicted this before we had the data to show it. And there's all kinds of theories and hypotheses around why this is the case. Underlying shared temporal limbic dysregulation, genetic factors, and so forth and so on. But the mechanisms underpinning epilepsy and psychiatric conditions are almost assuredly shared in some way. So when it comes to psychiatric symptoms, I think about how would I characterize them, how would I categorize them, and how would I think about the etiologies, again, that are giving rise to them. And these may include periictal or interictal, the idea of that a neuropsychiatric symptom is somehow temporally correlated with the ictus, with the seizure itself. Could it be the consequence of psychiatric and behavioral side effects of anti-seizure medicines? We'll talk more about that in a moment. Could this be post-traumatic epilepsy and related to a lesion that has disrupted networks in the brain responsible for emotion, cognition, or behavior? So let's think a bit more about the periictal and interictal phenomenon. So I think this is a helpful way for us to characterize neuropsychiatric symptoms. However, it itself is a bit too simplified. But the idea of periictal divided between preictal, occurring in those hours to days before a seizure, not to be confused with what we would previously call an aura, and aura is the ictus, but in the hours to days prior. And studies have shown that patients describe, and I'm sure this will be quite familiar to many people in the room, the most common periictal symptom of doc, I just get this funny feeling that builds up until I have the seizure. This funny feeling, it's kind of vague, nondescript. And just behind that, irritability, anxiety at the top of that list as well. Ictal phenomena, so of course this depends on the particular epileptogenic focus, and then the network surrounding it that become involved as it disseminates. But ictal fear in the amygdala. Jamevu and deja vu, and depersonalization, derealization in those mesial temporal structures. Complex hallucinations in the temporal lobes, or simple hallucinations like phosphenes or geometric shapes in the occipital lobe. We think about the idea of autoscopy, someone hallucinating themselves, seeing their own image in a mirror, has been correlated with seizure activity in the temporoparietal junction. Out-of-body experiences with disruptions of the brain's ability to map visual input onto extra personal space, and others as well. Alice in Wonderland syndrome, visual association cortex with micropsia, macropsia, metamorphopsia. And then postictal symptoms. So the one that we probably think about the most because it readily comes to the attention of clinicians and can be an emergency, is postictal psychosis. But you can also see postictal depression, postictal mania and hypomania. You can see postictal suicidality. And Andre Kanner and his team did a survey of 100 patients living with pharmacoresistant epilepsy. And what they found was that 3 4ths of patients had at least one postictal symptom with at least half of their seizures. So something to certainly be mindful of. Interictal neuropsychiatric conditions. So again, we can think of all the typical DSM labels that we would use, major depressive disorder, bipolar disorder, schizophrenia. However, one of the things about epilepsy is it reminds us of certainly the arbitrary divide between neurology and psychiatry. But it also reminds us of some of the pitfalls of our diagnostic structures, our nosology in the DSM. That many of the conditions that patients live with who have epilepsy, their psychiatric comorbidities, they don't quite always fit into those categories. And so we see things, ideas like interictal dysphoric disorder or the schizophrenia-like psychosis of epilepsy. But namely interictal, meaning that there's not a very clear-cut temporal association with the ictus. But as Dr. Trimble reminded us earlier, perhaps that's an imperfect way to think about this. A bit about anti-seizure medicines. So of course this is incredibly important, not just because of the potential for side effects, but if there's an exacerbation of psychiatric symptoms leading to poor adherence, perhaps discontinuation, and poor outcomes, poor outcomes that can be defined as impaired psychosocial functioning, suicide, SUDEP, worsening of psychiatric symptomatology, all certainly relevant. Some guiding principles of the neuropsychiatry of anti-seizure medicines. So always asking ourselves, does the patient in front of me have a history of a psychiatric condition? Or also I think pertinent is a family history. And we know that that history, a family history or personal history, will increase the risk of a psychiatric side effect with anti-seizure medicines. Am I introducing an anti-seizure medicine that is going to induce hepatic metabolism of other psychotropics that are playing really important roles in the treatment of psychiatric comorbidity? It's gonna chew it up and be less effective. The classic example from the literature is that if somebody's on a therapeutic dose of carbamazepine and they're on 800 milligrams of quetiapine, of Seroquel, that's a hefty dose of quetiapine. If you test the level of quetiapine in their blood, it cannot be detected. It cannot be detected. It's basically that they're taking a sugar pill. Am I introducing an anti-seizure medicine that may have a higher predilection to psychiatric side effects? Of course, classic examples that we think about quite often are levotiracetam and increasingly parampanil. We'll talk a bit about why that might be. And, or am I removing a medicine that may have had a mood-stabilizing property? The classic examples from psychiatry, valproic acid, carbamazepine, lamotrigine are mood-stabilizers for bipolar disorders, as well as others that can fall into that category. So this is a bit of a rough guide to think about what are those agents that may have lower risks of psychiatric side effects and those that may have higher risks. And the reason I say this is a rough guide is that we can never predict for one individual, we can never perfectly predict for one individual how they're going to tolerate an anti-seizure medicine. I can think of patients who came in and said, thank goodness, thank goodness the doctor got me off the Briviac and put me on Keppra, I'm doing so much better. And that just humbles me because it reminds me that we can't always exactly predict. But based on group studies, based on lots of analyses that we have in the literature, we have a pretty good feel for what's more likely and what's not. And some common themes that emerge from that data are that those anti-seizure medicines that modulate AMPA or potentiate GABA seem to have a higher correlation with psychiatric and behavioral side effects, whereas those that are sodium ion channel modulators, thinking about azolicarbazepine, carbamazepine, oxcarbazepine, lacosamide, and so forth, typically less of that risk. So a bit about pharmacoresistant epilepsy and epilepsy surgeries. I certainly don't have to tell this crowd the epidemiology of epilepsy prevalence, but that close to a third of patients with focal onset epilepsy may have pharmacoresistant epilepsy. And the surgical procedure, the surgical procedure that we know the most about, just because it's been around the longest and we have the most studies about, are for focal temporal lobe epilepsy, the anterior temporal lobectomy, which can lead to a clinical seizure freedom rate of two-thirds of patients, patients who may have had multiple trials of anti-seizure medications and a longstanding history of poorly controlled seizures. And if you survey those patients, years after the fact, over 90% will say that the surgery was worthwhile. Now, in patients who are candidates for epilepsy surgery, when we look at psychiatric comorbidity prevalence rates before and after surgery, we see that they're substantially higher than the general population. They're higher than patients who don't have pharmacoresistant epilepsy. After surgery, you can see de novo psychiatric complications with depression and upwards of a quarter of patients, anxiety disorders, numbers quite similar. Psychotic disorders, postictal psychosis, pre-surgery of about 7% of patients with medication-resistant epilepsy and higher rates of interictal psychosis as well. And some patients can develop postictal psychosis or interictal psychosis for the first time after an anterior temporal lobectomy. And suicide rates. The suicide risk is about 13 times that of the general population in those immediate months after surgery. And this seems to be independent from whether or not they attain seizure freedom. So, surgical outcomes as it relates to psychiatric outcomes. There's been systematic reviews that find that by a year after surgery that patients are either doing as well or at least not worse than they were pre-surgery. While other prospective studies have found substantial improvements in a whole range of psychiatric symptom domains a year out. And a retrospective study by Dr. Kanner and his team found that using laser interstitial thermal therapy, LIT, for temporal lobe epilepsy, that of those patients who had comorbid depression and anxiety, over 60% had remission following LIT. So, I think about epilepsy surgery as in its own way a psychiatric treatment, a psychiatric intervention. But the important thing to be mindful of is the window of vulnerability after surgery. So, in that first three to six months, perhaps up to a year, that is a period of time where psychiatric decompensation may be at higher risk. Not a certainty by any means, but something to monitor for, to have follow-up for, to make sure to ask about in follow-ups. So, what is still needed? Well, we need more mental health clinicians embedded into our epilepsy centers. Beyond a shadow of a doubt, we have to do better at that. The last time, as far as I know, this data was collected from epilepsy centers across the country. Only about a quarter had a mental health clinician embedded. We need more prospective, longer-term studies. We need to understand psychopathology outside the restraints and confines of how the DSM diagnoses it, and actually use or be able to utilize epilepsy as a new paradigm of understanding psychiatric conditions that occur outside of epilepsy, or what we would call idiopathic or primary psychiatric conditions. And to find biomarkers that can help us stratify and predict a particular individual patient's response to epilepsy surgery as it relates to mood and other psychiatric phenomena post-operatively, sort of the idea of precision medicine. So, I'll leave you with just saying we absolutely need mental health clinicians on teams. It's instrumental to the comprehensive, multidisciplinary care of patients with epilepsy. Psychiatric comorbidities are common. They likely have shared underpinning mechanisms with epilepsy itself, and most importantly, they are treatable. I spend a substantial amount of time working with colleagues who may not have as much familiarity or experience in caring for patients with epilepsy and their mental health comorbidities, and saying, yes, we absolutely can treat these patients. We can treat them with psychological interventions. We can treat them with psychopharmacologic interventions. There's some nuances to that, but I find that there's a lot of hesitancy out there in the healthcare community with prescribing psychotropics when indicated. And a call to action to reach out to your departments, your departments of neurology, your departments of psychiatry and psychology, your healthcare systems, your academic centers, and say, please, please support us in this mission. Please help us integrate to hire mental health clinicians on our teams. I think I just heard today at Cleveland Clinic there is a psychiatric APP in the EMU, too, too. Oh, I was gonna say you're ahead of the curve, but you're way ahead of the curve. Curve didn't have a chance. So to have a little call to action for that. I'll close by saying that it's truly a privilege. I predominantly care for patients with epilepsy as well as patients with functional neurological disorder, and it's truly a privilege every day to go to clinic and ask questions along the lines of, how does this three-pound organ with 100 billion neurons and a quadrillion synapses somehow give rise to the human condition? But to ask that question always in the service of easing the suffering of another human being, every day feels very meaningful doing that. Thank you all. Thank you.

epilepsy care

mental health

neuropsychiatric symptoms

psychiatric comorbidity

treatment outcomes