Okay. So, for our first speaker, it is a distinct honor for me to introduce Dr. Olga Tereshchenko. I have known Olga for a number of years as a close friend and colleague since the time that she did her epilepsy fellowship at Emory. Dr. Olga Tereshchenko is Associate Professor and Director of the Epilepsy Program at the University of Nebraska, and she also directs the Autoimmune Epilepsy Laboratory. She leads translational research on refractory seizures and autoimmune encephalitis. She's been recognized with numerous awards and grants, and no doubt you've seen some of her work here at this meeting. But today, we've asked her to talk about a very different topic that I think is very personal to her. She's going to focus on the treatment of epilepsy and maintaining adequate epilepsy treatment in conflict zones and war-affected areas with a specific focus on her home country of Ukraine. Dr. Tereshchenko. Good afternoon, everyone. Thank you so much for this great introduction and for inviting me to speak today. Well, it's always a great opportunity to speak at the AAS, and I'm usually fueled by this enthusiasm, and I work on my slides, and I'm usually way ahead of that CME deadline, but this time it was different. It was difficult. I had to start and stop making those slides, and I almost missed that deadline. But it was difficult because it was challenging to separate my personal and very painful take on the war and make sure that the information that I'm providing is useful for the large audience. As Dr. LaRose has mentioned, I am Ukrainian. As many of you in this audience, I've been living in this country for many years, but the rest of my family, except for my immediate family, live in Ukraine, in Kiev, and we also have several members who have been fighting in the front lines, defending the country, and so we've been enduring quite a hardship for the past two years. And as I was preparing this talk, another terrible war broke out in Israel, and it made me believe that, yes, we need to talk about what our patients are going through in those war-affected territories, and we have to learn how we can better take care of these patients. Those are my disclosures. They are not relevant to this talk. For the learning objectives, we will analyze the scope of activities directed to support epilepsy patients and providers during the war in Ukraine. We will also look at the recent recommendations by the International League Against Epilepsy for rapid agent conversion at the time of crisis and severe medication shortages, and then we'll discuss how healthcare delivery for seizures during wartime can also inform future disaster preparedness. Well, why do we care about epilepsy treatment in war-affected areas? Some of you can make an argument that the AIS community is largely comprised of Americans, and so we should be focused on the issues pertinent to North America. However, if you look at this diagram from the last year participation, and as you know, that was an in-person meeting, the majority of the attendees are, in fact, from the USA and Canada, but also we have a sizable proportion of participants who come from Europe, primarily from Great Britain, as well as Asia and Middle East, primarily from Japan, as well as other continents. So we do have a lot of international members who reside in all continents, and also the U.S.-based members are connected globally, either through their professional connections or through family connections, and if you look at the right or left-hand side, you will probably find those people in this audience. Another argument that one can make that I live in the U.S. and the war is not possible in my soul, well, over the past two years we've learned that geopolitical landscape is very complex and ever-changing, that the wars can occur suddenly, they are unanticipated and devastating, and we have to be prepared to support our colleagues abroad, and also be ready to learn new skills, and I'm not only talking about some medical or technical skills, I'm also talking about something that we never done in our careers, probably, such as fundraising or building relationship with pharmaceutical companies. Finally, another misconception may exist that if a large-scale conflict occurs here, there will be a quick and coordinated response from the medical community, but in fact the medical community is all of us here, and by and large our system, medical system, healthcare delivery system, is not built for disaster preparedness, despite our experience with COVID. Our healthcare system is inflexible, very complex, relies on advanced technologies, and one recent example I can give you is that the pipe broke down next to one of the hospital buildings, and we were down for a number of weeks with all our EEG, EMG, and MAG recordings. Another example was a cyber attack a couple years ago when all monitoring was stopped for several weeks. Finally, we as practitioners lack training in tactical medicine, and this is not only hands-on skills, but the entire philosophy of delivering care is completely different among us than it is in medics who are delivering care at the front lines, because they are focused on channeling their resources into caring for patients who most likely survive their injuries, which is completely opposite to the philosophy that we learn in medical school and practice in our day-to-day activities, saving every patient's life. So, hopefully, lessons learned from Ukraine can be applied to other medical conflicts. Let me tell you a little bit about the invasion. As you know, on February 24, 2022, there was an unprovoked and full-scale invasion by the Russian Federation. The size of Ukraine is close to the area of Texas, and you can see this map on day 14 of the invasion. The red areas are occupied, so within two weeks, about 20% of the territory was occupied by the Russian Federation. And I have to tell you that the magnitude of atrocities, the scale of atrocities committed towards the civilian population, and we see it over and over, like we see it in Israel's war, too, the magnitude of atrocities was truly unprecedented, and that included basic limitations for basic medical care and medications for those civilians from the occupied areas. Well, it's truly a genocidal war, and a lot of targets were aimed at health care facilities, and some of those pictures met the headlines. This is a bombing of the maternity ward in Mariupol, which is a city on the Azov coast. You can see that responders are carrying this pregnant woman. Unfortunately, neither the woman nor her child survived the injuries. This is a picture shared by my colleague who visited recently deoccupied Kharkiv area. You can see completely destroyed rural ambulatory center and horrifying pictures of bullet casings in a CT scanner where Russian soldiers were staged. Finally, a lot of power grid was targeted with missile strikes, and hospitals were not prepared to switch to the generators at that time. Only a few of them had it. This is a video which went viral of the pediatric heart surgery in Kiev, the capital, when during the blackout, all the equipment switched, including the artificial circulation, switched to the generator, and the surgeons were able to successfully complete the surgery. Overall, there was a massive destruction and closure of treatment facilities. By June 2023, when the last WHO report was available, over 1,000 attacks took place at the health care facility. There was constant danger of shelling for patients and health care workers, and those facilities that were spared from bombing were overwhelmed with wounded delivered from other decimated cities. That resulted to disruption of pharmacy network. The medications were not delivered into the hospitals or pharmacies, and there was a limited or discontinued urban and suburban transportation system. Finally, a lot of physicians and nurses died or relocated to other areas. This map shows a missile strike on one day in October 2022, when over 70 missiles were hitting those large cities, which has population over a million and primarily targeting civilian infrastructure, including the hospitals. A couple of words about the pre-epilepsy care in Ukraine. The population of Ukraine prior to war was close to 43 million, and there were about 250,000 patients with epilepsy, of which were about 42,000 children. The consultative care for drug-resistant epilepsy was established in five large cities. At those centers, they had epilepsy case conferences with U.S. neurosurgeons. This organization, RASOM for Ukraine, which stands for Together for Ukraine, was established by the neurosurgeon from New Jersey that allowed to prepare or train Ukrainian neurosurgeons in epilepsy surgery and tumor surgeries within the U.S. and Canada. The volumes were close to 100 surgeries per year. They were conducted at three large centers and included ATLs, lesionectomies, corpus callosotomies, and rare VNSs because they are not supported by the state insurance. Within the first weeks of war, there was a massive relocation of patients with epilepsy. Close to 50,000 to 80,000 patients left the country to the neighboring European countries, and another 50,000 got internally displaced. You can imagine that that created a major chaos in delivery of care for those patients. While international organizations were providing medications, medications for neurological conditions were not their focus. They were focused on antibiotics, pain medications, blood products. The burden of treating those patients really fall on to the organizations, professional organizations. The International League Against Epilepsy quickly created emergency response task force, and that call was answered by several large European organizations, such as European Academy of Neurology, European Pediatric Society, as well as Society for Neurosurgery, and these organizations largely helped to establish care for those patients who left the country and also helped with telemedicine consults and also some medication delivery. At the level of AAM, there was a Ukraine crisis response work group, and most importantly, there were major efforts, grassroots efforts by several neurologists and epileptologists, which, in my opinion, made the largest, the most significant difference in care of those patients. While within first weeks of war, the letter was published by Dr. Dubenko, who is the head of Ukrainian League Against Epilepsy, noting the critical need for all ACMs. That letter was published in Lancet and become rapidly available to global audience. There was also a telephone survey of the Ukrainian members of International League Against Epilepsy regarding the need for medications, which was conducted over the phone, and the survey noted over 2,000 children in the registry, and only, you know, one third of them had available medications in only for two weeks. Can you imagine how terrifying it is to know that your patients cannot get to anti-seizure medications beyond two weeks? This is the results of that survey for adults and children on the left and right-hand side, and you can see that majority of patients were receiving on a regular basis carbamazepine, levatoracetam, and valproate, as well as some other medications in pediatric population, and those three top medications are on WHO must-have list, as you remember that lecture a couple days ago. But there was also a shortage of rescue medications, including benzodiazepines in all forms and injectable forms of valproate, levotriacetam, and finitoin. These physicians had made a major contribution in helping to establish viable supply of medications to the patients in Ukraine. So Dr. Tuchkivska is a pediatric epileptologist from Lviv. She was recently trained at Sick Kids in Toronto and had very well-established ties with her colleagues, Dr. Killing and Dr. Abbott from Boston Children's, and they were joined by Dr. Fakturovich from Boca Raton Hospital, who is a neurologist there. So they made titanic efforts to establish this sustained delivery system. So they started with obtaining information from the local physicians and patients, and that was pretty much the Excel spreadsheet with names of patients and addresses. Then Dr. Fakturovich and her colleague worked to establish connections with vendors, including pharmaceutical companies in the United States, Germany, Israel, India, and other countries, asking them to either donate medications or provide them at the wholesale prices. Finally, they needed to establish delivery system, and in my experience, that's the most expensive part. So they found logistic companies and nonprofit organizations, which were allowing to ship those medications overseas for free. And then established the delivery corridors locally, mostly through Poland to Ukraine, and that was done also through the help of local nonprofit organizations. Well, this squares look very simple, but this is a months and months, weeks of efforts of those physicians who never had any experience with wholesale purchasing or working with nonprofit organizations or with fundraising. So that's the skills that these doctors have raised, and Dr. Fakturovich was very successful with her group, raising close to half a million dollars for purchase of ASMs, and we, with our smaller group, raised close to $50,000 for tactical medical supplies, which included tourniquets, hemostatic devices, and burn dressings, et cetera. So I want to give applause to these physicians who found time in their busy careers to bother and worry and help those patients in need. The greatest challenges in their experience was obtaining and shipping controlled substances, especially benzodiazepines. Virtually every vendor said no to that because they were not comfortable providing those medications. So Dr. Fakturovich reached out to the Israeli government through the personal connections, and Israeli government helped to purchase those medications in Israel, and those included clobazem and clonazepam, very much needed for children with infantile spasms and other pediatric encephalopathies, and they were able to not only ship them in large quantities, but continue to deliver them at regular intervals. The other challenge was purchasing medications at the wholesale price. This is nothing that physicians know how to do. Dr. Fakturovich was able to establish an account with her hospital pharmacy, and was able to purchase those medications, and she was telling me how much levotrastamine and valproate cost, and none of us ever had those answers prior to that. And then finally, the challenging part was communicating with recipients locally in Ukraine to make sure that medications reached the physicians and children and adults who needed them. Initially, the effort was made to even deliver those medications into the occupied regions. However, after several volunteers were killed by Russian soldiers, that effort was abandoned, and the medication delivery at this stage only occurs to the Ukrainian-controlled territories. Those are pictures of actual patients who received those medications and continue to receive them through this program. You can see this is very rewarding to see smiles of those kids who otherwise probably would suffer from status or potentially could die. AEN also got involved. They created Ukraine Crisis Response Work Group, which was chaired by Dr. Lyle Jones, and really, the effort was to help local neurologists in Ukraine not only with anti-seizure medications, but also medications for MS, Parkinson's disease, et cetera. And then the goal of this group was to create a roadmap for future wars and future crisis, how to address similar challenges in the future. So they obtained report from AEN members in Ukraine on local needs, including medications, created a database of Ukrainian-speaking and Polish-speaking members who could conduct telehealth services for consultations. And then Dr. Ovitser, who was AEN president at that time, placed a personal call to the stakeholders from the industry roundtable to either donate or sell anti-seizure medications at low prices. This is a list of people who are involved in this initiative. It's not a comprehensive list, but you can see a lot of our colleagues here. And if I forgot to include somebody here, please forgive me. And many thanks to all these physicians. The International League Against Epilepsy has placed a call to the leading expert in the field responding to this crisis with medication shortages to develop recommendations on rapid ASM conversions at the time of crisis when the patient's traditional medications are not available. You can see that those overnight transitions exist only for a few medications. And enantiomers and congeners of carbamazepine can be readily switched overnight. And in the right-hand side, you can see the dose adjustments that we have to follow. Also, clobazum can be transitioned to clonazepam, but remember that it's less potent, much less potent than clonazepam. Also, breviracetam can be transitioned to levitracetam, and primidone can be swapped with phenobarbital. However, this is a very short list of medications. For the majority of other agents, such overnight rapid transitions do not exist, and we have to use a different strategy. First, we have to identify a syndrome, prepare a list of appropriate or contraindicated ASMs based on our knowledge of pharmacokinetics, and then transition with at least one overlapping dose. Several points have to be kept in mind that the initiation of carbamazepine will still require a titration, preferably over the course of two to three weeks. However, it can be accomplished sooner, and we can start at the one-third of the target dose and increase it every couple days by 30%. Other medications, such as lamotrigine, topiramate, and zonisamide, would be better off to be titrated to avoid breakthrough seizures, and for that, we can use benzodiazepine bridge, which can be accomplished with any benzodiazepine, and I included the example here for clonazepam. And then once the medication reaches the target dose, then benzodiazepine can be slowly tapered off over the course of seven to 14 days. This benzodiazepine transition should be avoided in elderly and other patients who are prone to develop delirium. And finally, brand to generic switch, as we all know, is relatively safe, but bioequivalency for extended release and sustained release preparations can vary. This is not something new. All of us are familiar with medications that best suited for adult syndromes, but my goal was here to highlight in red medications that can be administered to all groups of patients, and for adult syndromes, you pretty much can safely transition to lamotrigine, levotriazepam, and leucosamide for all syndrome. For pediatric patients, there are also such similarities, and for infantile spasms and benoxgestose syndrome, as well as other pediatric syndromes, we can transition to topiramate and zonisamide virtually in any case. Finally, there are substitutions, very surprising substitutions that I learned about in seizure emergencies that we actually obtained from the field of palliative medicine, that if benzodiazepines are not available, we can use carbamazepine immediate release tablets or oral suspension, valproate syrup, or injectable preparation, or even lamotrigine crush tablets in a liquid, and all of these preparations can be administered rectally in a large volume of liquid, and also with a typical rescue doses that we traditionally use otherwise. Surprisingly, phenytoin, lorazepam, and midazolam, as much as they are effective in other routes, are poorly absorbed through the rectum, so they should not be administered for that indication. Going back to the Ukraine and the war, the group of physicians that I mentioned continue to focus on supporting patients in Ukraine, and they help with purchase of eight EEG machines, as well as VNS tablet and neurorehabilitation equipment, which is much needed now, as well as telemedicine services that are currently provided by several nonprofit organizations. And then the focus is on emerging medical needs, such as TBI and related epilepsy, secondary to heart trauma, and then prosthetics, which are really a big problem. So Ukraine is a nation of amputees currently, close to 50,000 people are in need for those prosthetics, and those are not only soldiers, but also civilians, including children. You can see this very complex amputations that they underwent. This first picture of amputated arm in a girl from Bucha, a suburb of the capital of Ukraine, due to gunshot wound, and she received prosthetics abroad, and is doing really well. And the second one is a young gymnast from Odessa, who was under the concrete wall for several hours before she was rescued, and that's how she lost her leg, but she received very nice prosthetic leg, and she returned back to competitive gymnastics. In summary, the opportunities in Ukraine and other war-torn regions exist at multiple levels. You can join if you're passionate about it, or if you have connections to the country that is in crisis, you can join international collaborations at the level of ANAS, or International League Against Epilepsy. Surprisingly, institutions many times have global health programs that are well-established, and I was surprised to learn how many our institution has. And then, at the individual level, connect with colleagues who share similar humanitarian aspirations, and engage your trainees, because many of them are very passionate about that. And also, you would be surprised that you'll find time for volunteering and learn the ropes of fundraising. This is what we have done at our hospital. Dr. Povoluri is our former epilepsy fellow. She's also a very talented artist. She painted a number of those beautiful paintings that we were able to auction and raise money for the medical supplies for Ukraine. And this is our medical personnel at the hospital that provided many donations of supplies. And right-hand side is our group of volunteers, which now includes our spouses, too. And then, on the right lower corner, you see the picture from Kherson city in Ukraine that received our donations. Finally, I would like to finish with this slide. What if the war is here? Do we have the patient registries, or we will be paralyzed without EMR? Will we need to do telephone interviews similar to what the Ukrainians did during the war? Is our ASM supply self-sustainable? Do we have vendors that will respond right away? Our transportation routes will not be affected? Will we be able to continue epilepsy surgeries? And will we have enough greed to sustain our patient care efforts? With that, I would like to thank physicians who were spearheading those efforts, Dr. Fakturovich, Kilian, Abbas, and Tuchkivska. I would like to thank the head of International League Against Epilepsy, Dr. Dubenko, our volunteers at UNMC. Sabrina So is a high school student from California who is very passionate about Ukraine and epilepsy. She helped me to prepare this presentation, and she is also leading small fundraising efforts in California. And finally, many thanks to two non-profit organizations, Brother Brother Foundation and Heartland Family Services, and specifically to their CEOs, Ozzy Samant and John Gennetta for helping us to continue our humanitarian efforts. And with that, I would like to thank everyone for listening. Thank you.

epilepsy treatment

conflict zones

medication shortages

anti-seizure medication

trauma-related epilepsy

crisis response