The symposium addressed the intricate relationship between epilepsy and other medical conditions. Dr Scott Mintzer kicked off the symposium with his talk “Epilepsy & Heart Disease: Tips for the Consultant.” He identified the impacts of anticonvulsants on the cardiovascular system and the interactions between antiepileptic drugs and cardiac medications. Hepatic enzyme inducing anticonvulsants are associated with worse lipid profiles and vascular risk markers and reduce the efficacy of some cardiovascular medications, such as statins.1 Older anticonvulsants, such as carbamazepine, may even be associated with increased risk of myocardial ischemia. Dr Steven Pacia presented “Syncope and Other Seizure Mimics,” where he reviewed key clinical features that distinguish seizures fromsyncope and other seizure mimics such as migraine, transient ischemic attacks, metabolic disorders, nonepileptic psychogenic seizures, transient global amnesia, and sleep disorders.Some, such as prolonged QT syndrome, should not be missed.Dr. Andres Kanner led the discussion on “Do Psychotropic and Antibiotic Drugs Cause Seizures? A Review of the Evidence.” He reviewed selection of antibiotics and psychiatric medications that would minimize seizure risk. Therapeutic doses of serotonin and norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants appear to be associated with reduced seizure incidence, though overdoses of these classes of medications can be associated with increased risk of seizures.Bupropion and clomipramine were the exceptions to the rule,vertical grow system and seizure risk was increased with these medications compared to placebo. Antibiotics may increase the risk of seizures.
The mechanism by which antibiotic lower seizure threshold may be decreased GABAergic activity. Dr Page Pennell discussed the management of AEDs during pregnancy to optimize seizure control and pregnancy outcomes in her talk “Seizure Management during Pregnancy.” Her presentation reviewed the teratogenic risk of AEDs and other pregnancy outcomes including “small for gestational age” .Valproate was also associated with lower IQ in childhood and increased risk of autism. On the other hand, folate prescribed before pregnancy or at start of pregnancy was associated with higher IQ and lower risks of autism. There are changes in pharmacokinetics of AEDs during pregnancy and dose adjustments are needed to maintain seizure control. Dr Jeanne Young discussed “Anticonvulsants and the Skin Hypersensitivity”. Dr Young emphasized the diversity in hypersensitivity associated with AEDs, distinguishing drug rash based on pathophysiology and clinical characteristics, and recognizing clinical features that could alert us to severe cutaneous adverse reactions. The most common type of reaction is a morbilliform rash with erythematous papules or plaques due to immune complex deposition and cell-mediated immunity. These rashes characteristically begin 7 to 10 days after starting medication and typically resolve in 2 to 3 weeks. Patients usually feel well, though they may complain of pruritis. Interestingly, in some cases it is possible to “treat through” the rash, or re-challenge later with the same medication, with the patient under close observation by dermatology. Signs characteristic of more severe drug reactions are swelling of the face, presence of pustules, bullae, or vesicles, dusky or painful lesions, mucous membrane involvement, or signs of systemic involvement. Morbilliform skin eruptions beginning later than expected along with systemic symptoms and patient feeling ill are more concerning for progressing to Drug Rash with Eosinophilia and Systemic Symptoms syndrome.
The neurobiology of memory has long been a central issue in epilepsy, particularly for syndromes involving mesial temporal lobe structures. While Ramon y Cajal first detailed the neuroanatomical structure of the hippocampus more than 100 years ago,it was the well-known case of “H.M.” that revealed the prominent role of the hippocampal formation and related structures in declarative memory.Patients undergoing temporal lobe resection for control of pharmacoresistant seizures may experience postoperative memory decline. Preoperative reorganization of the posterior hippocampus with transfer of function to contralateral and extratemporal structures including anterior cingulum and insula may be a key factor in preservation of memory function,and there may be a role for memory functional magnetic resonance imaging studies in individualized outcome prediction.There is also evidence that the choice of surgical approach has important implications for postoperative memory outcomes.Even apart from surgical intervention, memory deficits are a common comorbidity in epilepsy. At the cellular level, seizureinduced epigenetic dysregulation likely plays an important— but little understood role. Abnormally regulated BDNF DNA methylation was explored in a rodent temporal lobe epilepsy model, and was shown to have a dual role in modulating both epileptiform abnormalities and memory impairments.Memory consolidation is an important mechanism supporting long-term memory that may also be disrupted by epileptiform activity. Studies of human multi-scale and animal recordings demonstrated locally recorded cortical replay of waking patterns during subsequent sleep periods.This process involves an intricate coordination of cortical up and down states, hippocampal sharp-wave ripples and thalamocortical spindle activity, with distinct roles played by the anterior and posterior hippocampus. Finally, building on the previous year’s symposium, early results from a recent high-profile study of the use of cortical electrical stimulation to improve memory function were presented.
In a promising development, successful enhancement of hippocampal-dependent memory in patients with epilepsy has now been reported with lateral temporal stimulation and independently in entorhinal white matter using q-burst stimulation.Emilio Perucca, MD, PhD, focused on the rational use of anticonvulsant medication and reviewed a systematic approach to sequencing and combining antiepileptic medications. Given the extensive choice of treatments, an evidence-based systematic approach is important when treating patients.The literature contains a number of comparative studies, though more evidence is needed, particularly when planning polytherapy. Different clinical scenarios were provided to illustrate his approach, and he highlighted areas in which further knowledge must be obtained. This approach to therapy, which is driven by data and experience, offers a masterful way to treat epilepsy. The second lecture, given by Dennis Dlugos, MD, “What’s in the Pipeline? Newly Approved and Almost Ready Antiepileptic Drugs” provided a review of both recently approved medications and drugs that are presently in the pipeline, but anticipated to enter the clinical arena. Professor Dlugos reviewed pivotal trial data, both with regard to efficacy and adverse effects. Pipeline drugs show promise for both generalized and focal epilepsy. It is hoped that the information provided in this lecture will enable the practicing physician to integrate the use of these agents into practice once they are available. The third lecture, delivered by Barbara Dworetzky, MD, reviewed rescue therapy, with a particular focus on new and emerging treatments. Trials have been conducted employing several benzodiazepines, including diazepam, midazolam, and alprazolam. These new therapies may be administered intranasally, or in the case of alprazolam, by inhalation, though the latter agent has only recently entered the trial phase. Professor Dworetzky reviewed the pharmacology and trial results; these preparations do not require rectal administration and may prove a popular choice by patients and their families when rescue is needed. The final lecture, given by Jukka Peltola, MD, reviewed deep brain stimulation of the anterior nucleus of the thalamus for intractable epilepsy. This therapy was recently approved by the Food and Drug Administration in the United States,indoor vertical garden systems but has been in use in Europe since 2011. Professor Peltola reviewed both clinical trial data and the European clinical experience, and proposed suitable indications for employing this therapy.The symposium encompassed topics ranging from basic science, translational research, clinical trials, adverse effects, nutritional guidance, and possible anti-inflammatory benefits. Dr Susan Masino covered “Cellular metabolism as a paradigm for experimental therapeutics in epilepsy.” She discussed the 4 major possible therapeutic targets of metabolism-based therapies: changes in blood and cerebrospinal fluid , improved mitochondrial function and energy reserves, synaptic stability, and cellular changes including alterations in the gut microbiota.Dr Kristina Simeone then tackled “Metabolic approaches for treating complications and comorbidities of epilepsy.” She focused on how these therapies have been shown in preliminary studies to benefit cognition, autism, behavior, sleep, and even SUDEP .Dr Elizabeth Donner reviewed “Clinical evidence for metabolism-based therapies in children: trials and guidelines.” In her lecture, Dr Donner first covered the strong evidence from multiple randomized controlled trials for ketogenic diet therapy, then provided an overview of the updated 2018 revised international consensus guideline.The fourth lecture was given by Dr Anita Devlin and was titled “Ketogenic Diet for Infants?”
Two specific epileptic encephalopathies affecting infants have evidence for treatment response to ketogenic diet.20 Dr Devlin ended by discussing the ongoing “KIWE” trial in the United Kingdom which has been enrolling infants 1 to 24 months of age into a randomized trial of the ketogenic diet versus further antiseizure drugs. Robyn Blackford, RD, provided a dietitian’s perspective on handling the adverse effects from these dietary interventions in a lecture entitled “Safety and prevention of risks from metabolism-based therapies.” Finally, Dr Stephane Auvin ended the symposium with a basic and clinical science lecture on “Are there anti inflammatory effects of metabolic therapies?”, with a focus on refractory status epilepticus and Febrile Infection-Related Epilepsy Syndrome .In summary, this symposium achieved its goal of highlighting how the ketogenic diet and other metabolism-based treatments have become “state of the art.” This symposium addressed bioethics in 4 areas: transition to adult care delivery of behavioral health services using technology self-management interventions and outcome measures, and anti-seizure medication. General ethical principles, including respect for autonomy, nonmaleficence, beneficence, and justice as they pertain to comprehensive care of persons with epilepsy were covered. Dr Eric Racine articulated the nuances of respect for autonomy in the transition from pediatric to adult care for persons with neurodevelopmental disabilities. Autonomy includes 6 component abilities: voluntariness , information , control , deliberation , authenticity , and enactment .Dr Hamada Altalib discussed ethics in employing technology to deliver behavioral health care to PWE, including specifically challenges related to consent, privacy, confidentiality, and the patient–provider relationship. Insight into howtele health and mobile health can improve justice and equity by removing barriers to care such as transportation and resource disparities. The VA Epilepsy Center of Excellence was presented as a model for mobile behavioral health care. Appropriately implemented technology can revolutionize the range and standard of care. Dr Martha Sajatovic covered self-management support and collecting behavioral outcomes. Given the high rate of mental health comorbidities and barriers to in-person behavioral health care, the SMART intervention contains one in-person session with a nurse educator-peer educator dyad and then 7 group sessions in a web-based format. Following SMART, PWE who had experienced a negative health event reported decreased depressive symptoms and improved quality of life versus people on a wait list.23 There are ethical considerations, such as group confidentiality and the role of patients as peer educators. Findings from 5 pooled managing epilepsy well network randomized controlled trials demonstrated a reduction in depressive symptoms following self-management interventions. Research relies on integrated research datasets.However, there are multiple ethical issues to consider, including protected health information, data sharing agreements, firewalls, and authorship. Dr Viet Nguyen addressed ethics in selection of AED therapy. Beneficence and nonmaleficence must be balanced when identifying epilepsy management goals and related costs, and the role of justice was also discussed. Patients express concerns with AED changes, and clinicians must manage adverse effects to promote improved quality of life. Patients have a right to choose their therapy and there must be the balance of autonomy of choice with adequate treatment.Caring for patients with epilepsy is both a science and an art. This statement has never been more accurate than today. Faced with an exponential growth in diagnostic technology and novel therapeutics, the variety of choices that we have to make have become much more complex. Yet, robust data on comparative effectiveness and for evidence-based decision making are lacking. This information deficit is at the root of the significant variation in our practices, and sub-optimal patient care. Considering several current controversies in the management of difficult epilepsies, some challenges stand out. First, the frequency and indications for some tests that are considered cornerstones of our epilepsy management remain highly variable and require balancing multiple factors, including the treatment goals of the patients, risks, alternatives, and cost. The indication for a video EEG study is a perfect example. This inpatient testing is warranted to confirm the diagnosis of epilepsy and rule out psychogenic nonepileptic seizures in patients who continue to have seizures despite 2 or more adequate and appropriate antiepileptic drug trials. Conversely, holding off the initiation of seizure medications until a diagnosis of epilepsy can be positively confirmed with video EEG is clearly inappropriate in patients at high risk of seizure related injuries, nocturnal convulsions with increased risk of sudden death in epilepsy, existing medical comorbidities , severeictal or postictal behavioral disturbance, and in resource-limited communities.