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There is a reciprocal relationship between epilepsy and reproductive endocrine disorders. Seizures and anti-seizure medications (ASMs) can contribute to reproductive and endocrine dysfunction and reproductive dysfunction may exacerbate seizures. Epilepsy via neuroendocrine mechanisms affects the hypothalamic–pituitary-ovarian (HPO) axis, disrupting the regulation of gonadotropin secretion, and resulting in dystrophic effects on the ovaries and early menopause. Anti-seizure medications have endocrine-related side effects on sexual function and bone health. Long-term use of ASMs may result in menstrual irregularities, sexual dysfunction, anovulatory cycles, polycystic ovaries, and reduced fertility. Some ASMs also interfere with bone metabolism. Epilepsy patients treated with ASMs are at risk for bone loss and fractures. This article explores the endocrine and hormonal effects of seizures and ASMs.

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia.

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New-onset refractory status epilepticus (NORSE) is a rare clinical presentation of refractory status epilepticus (RSE) that occurs in people without active epilepsy or preexisting neurologic disorder. Febrile infection-related epilepsy syndrome (FIRES) is a subcategory of NORSE. New-onset refractory status epilepticus/FIRES are becoming increasingly recognized; however, information pertaining to disease course, clinical outcomes, and survivorship remains limited, and mortality and morbidity are variable, but often high. The objective of the NORSE/FIRES Family Registry is to (1) provide an easily accessible and internationally available multilingual registry into which survivors or NORSE/FIRES surrogates or family members of people affected by NORSE/FIRES or their physicians can enter data in a systematic and rigorous research study from anywhere in the world where internet is available; and (2) to examine past medical history, outcomes, and quality of life for people affected by NORSE/FIRES.

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Epilepsy is a chronic disease with multiple, complex comorbidities. Bidirectional relationships exist among seizures, sleep, circadian rhythms, and diseases within and outside of the central nervous system. Seizures fragment sleep and can contribute to development of sleep disorders, which in turn leads to worse overall health and more seizures. Moreover, treatment options are often limited by interactions with anti-seizure medications. Advances in the fields of epilepsy and in sleep medicine have been made separately, and therefore treating patients with these comorbidities necessitates interdisciplinary approach. The focus of this section of the Sleep and Epilepsy Workgroup was to identify methods of collaboration and outline investigational, educational, and treatment priorities to mutually advance what we consider a combined field.

Neuroimaging techniques, particularly magnetic resonance imaging, yield increasingly sophisticated markers of brain structure and function. Combined with ongoing developments in machine learning, these methods refine our abilities to detect subtle epileptogenic lesions and develop reliable prognostics.

The study of high frequency oscillations (HFO) in the electroencephalogram (EEG) as biomarkers of epileptic activity has merely focused on their spatial location and relationship to the epileptogenic zone. It has been suggested in several ways that the amount of HFO at a certain point in time may reflect the disease activity or severity. This could be clinically useful in several ways, especially as noninvasive recording of HFO appears feasible. We grouped the potential hypotheses into 4 categories: (1) HFO as biomarkers to predict the development of epilepsy; (2) HFO as biomarkers to predict the occurrence of seizures; (3) HFO as biomarkers linked to the severity of epilepsy, and (4) HFO as biomarkers to evaluate outcome of treatment. We will review the literature that addresses these 4 hypotheses and see to what extent HFO can be used to measure seizure propensity and help determine prognosis of this unpredictable disease.

Intracranial electroencephalography (iEEG) has been the mainstay of identifying the seizure onset zone (SOZ), a key diagnostic procedure in addition to neuroimaging when considering epilepsy surgery. In many patients, iEEG has been the basis for resective epilepsy surgery, to date still the most successful treatment for drug-resistant epilepsy. Intracranial EEG determines the location and resectability of the SOZ. Advances in recording and implantation of iEEG provide multiple options in the 21st century. This not only includes the choice between subdural electrodes (SDE) and stereoelectroencephalography (SEEG) but also includes the implantation and recordings from microelectrodes. Before iEEG implantation, especially in magnetic resonance imaging -negative epilepsy, a clear hypothesis for seizure generation and propagation should be based on noninvasive methods. Intracranial EEG implantation should be planned by a multidisciplinary team considering epileptic networks. Recordings from SDE and SEEG have both their advantages and disadvantages. Stereo-EEG seems to have a lower rate of complications that are clinically significant, but has limitations in spatial sampling of the cortical surface. Stereo-EEG can sample deeper areas of the brain including deep sulci and hard to reach areas such as the insula.  To determine the epileptogenic zone, interictal and ictal information should be taken into consideration. Interictal spiking, low frequency slowing, as well as high frequency oscillations may inform about the epileptogenic zone. Ictally, high frequency onsets in the beta/gamma range are usually associated with the SOZ, but specialized recordings with combined macro and microelectrodes may in the future educate us about onset in higher frequency bands. Stimulation of intracranial electrodes triggering habitual seizures can assist in identifying the SOZ. Advanced computational methods such as determining the epileptogenicity index and similar measures may enhance standard clinical interpretation. Improved techniques to record and interpret iEEG may in the future lead to a greater proportion of patients being seizure free after epilepsy surgery.

Insular seizures are great mimickers of seizures originating elsewhere in the brain. The insula is a highly connected brain structure. Seizures may only become clinically evident after ictal activity propagates out of the insula with semiology that reflects the propagation pattern. Insular seizures with perisylvian spread, for example, manifest first as throat constriction, followed next by perioral and hemisensory symptoms, and then by unilateral motor symptoms. On the other hand, insular seizures may spread instead to the temporal and frontal lobes and present like seizures originating from these regions. Due to the location of the insula deep in the brain, interictal and ictal scalp electroencephalogram (EEG) changes can be variable and misleading. Magnetic resonance imaging, magnetic resonance spectroscopy, magnetoencephalography, positron emission tomography, and single-photon computed tomography imaging may assist in establishing a diagnosis of insular epilepsy. Intracranial EEG recordings from within the insula, using stereo-EEG or depth electrode techniques, can prove insular seizure origin. Seizure onset, most commonly seen as low-voltage, fast gamma activity, however, can be highly localized and easily missed if the insula is only sparsely sampled. Moreover, seizure spread to the contralateral insula and other brain regions may occur rapidly. Extensive sampling of the insula with multiple electrode trajectories is necessary to avoid these pitfalls. Understanding the functional organization of the insula is helpful when interpreting the semiology produced by insular seizures. Electrical stimulation mapping around the central sulcus of the insula results in paresthesias, while stimulation of the posterior insula typically produces painful sensations. Visceral sensations are the next most common result of insular stimulation. Treatment of insular epilepsy is evolving, but poses challenges. Surgical resections of the insula are effective but risk significant morbidity if not carefully planned. Neurostimulation is an emerging option for treatment, especially for seizures with onset in the posterior insula. The close association of the insula with marked autonomic changes has led to interest in the role of the insula in sudden unexpected death in epilepsy and warrants additional study with larger patient cohorts.

Objective: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. Methods: Systematic review of evidence; modified Grading Recommendations Assessment, Development and Evaluation process for developing conclusions; recommendations developed by consensus. Results: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0–17 years) is 0.22/1,000 patient-years (95% CI 0.16–0.31) (high confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64–2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). Recommendations: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.