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. Giventhe 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. 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,weed curing 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, 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.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, non-maleficence, 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.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 non-maleficence 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,drying cannabis 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 non-epileptic 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 , severe ictal or postictal behavioral disturbance, and in resource-limited communities.
Similarly, it is important to check the blood levels of seizure medications when changes in metabolism are expected or in the context of suspected toxicity, but a routine practice of blood-level monitoring is a waste of time and resources.Second, better evidence is needed to guide the initiation, choice, and discontinuation of seizure medications. For example, while traditional seizure medications such as clobazam may be highly effective to treat pediatric drop attacks, newer but significantly more expensive treatments are now avaiable. Without robust analyses comparing the effectiveness and the cost of the traditional versus novel medication options, the choice of the ideal treatment remains controversial.Another glaring controversy is the timing and safety of medication withdrawal after successful epilepsy surgery where patient goals of independence and freedom from cost and adverse effects of seizure medications must be weighed against the risks of recurrent breakthrough seizures and downstream effects of reinstated seizure precautions such as driving restrictions.28 Lastly, the recent increase in the use of invasive electroencephalography recordings brings with it its own challenges to define indications and ideal methods for intracranial evaluations. Sub-dural electrodes have the advantage of permitting extraoperative ictal recordings in addition to mapping of eloquent cortex. Stereo EEG evaluations offer the ideal intracranial method for electroclinical correlations of an epileptic network.Intraoperative electrocorticography has been equally successful in guiding surgical resections based on definition of epileptiform repetitive discharges. Given the lack of any direct comparative effectiveness studies and similar published long-term outcomes, the choice of one invasive EEG method over the other is largely dependent on the expertise of a center’s neurosurgical and epileptology faculty. In summary, controversies and epilepsy management abound, reflecting a need for more robust data.The symposium addressed topics related to the consequences of febrile status epilepticus in children and in developing animals. The goal was to address the consequences including hippocampal injury and development of hippocampal sclerosis and mesial temporal lobe epilepsy.Dr Dale C Hesdorrfer addressed the epidemiology of status epilepticus and where FSE fits in. In new ILAE definitions of SE while for treatment purposes, the revised definition is 5 minutes, for the study of consequences, the 30-minute definition remains appropriate. Time to treatment unfortunately remains much longer than we would like. Mortality of SE, while primarily a function of etiology, remains substantial. Febrile status epilepticus rarely stops on its own without administration of AEDs. Dr Shlomo Shinnar, who moderated the symposium, then discussed data on the consequences of FSE with an emphasis on results of the FEBSTAT study .Hippocampal injury as reflected in increased hippocampal T2 signal on magnetic resonance imaging occurs in about 12% of cases. When hippocampal injury is present, there is substantial shrinkage of the hippocampi within a year and development of anatomic hippocampal sclerosis, though epilepsy has likely not yet developed. Children with evidence of acute hippocampal injury had a different cytokine profile than those without such evidence and from those with a fever but no seizure.As a group, children with FSE had somewhat smaller hippocampi at baseline than a control group with simple febrile seizures.Subsequent hippocampal growth is impaired in children with febrile SE. Dr David Masur then presented data on cognitive outcomes of children with FSE.Data from prior studies, most of which did not explicitly study memory, were reviewed. In FEBSTAT, overall intelligence was normal. In children with evidence of acute hippocampal injury, memory as measured by the Wide Range Assessment of Memory and Learning particularly verbal memory, was impaired 5 years later. This is even in the absence of epilepsy. In children with normal imaging memory appears to be intact. Dr Tallie Z Baram then presented the animal data that help explain findings in humans. In immature rats, hyperthermia produces seizures. Susceptibilty is influenced by genetic background but can be reliably reproduced in immature rodents. Febrile status epilepticus produces epilepsy after a silent period with duration of FSE determining severity of resulting epilepsy.Febrile status epilepticus also results in enduring memory deficits with impaired function of hippocampal place cells. Inflammation may play a key role. An improved understanding of the mechanisms involved can inform future trials to prevent development of epilepsy and memory deficits following febrile SE.There is a known and close interaction between sleep and epilepsy. Understanding this complex relationship has far reaching implications. It is now evident that risk of interictal activity and seizures in different human epilepsy types and syndromes varies depending on sleep states, and rapid eye movement stage is universally the least permissive to seizures.However, little is known about the effects of state transitions on seizures, and experimental research suggests an increased risk of seizures in transitions from REM.But what may be the molecular correlates of the circadian variation of epileptic excitability?