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Seizure freedom is recognized as the goal of epilepsy treatment by patients, families, and in treatment guidelines and is associated with notably improved quality of life. However, many studies of epilepsy treatments (including antiseizure medications/antiepileptic drugs, neurostimulation, and dietary therapies) fail to report data on seizure freedom. Even among studies that include this outcome, methods for defining and analyzing seizure freedom vary considerably. Thus, the available data are often difficult to interpret and comparisons between studies are particularly challenging. Although these issues had been identified over a decade ago, there remains a lack of clarity and standardized methods used in analyzing and reporting seizure freedom outcomes in studies of epilepsy treatments. In addition, it remains unclear whether short-term seizure freedom outcomes from pivotal clinical trials are predictive of longer-term seizure freedom outcomes for patients with treatment-refractory epilepsy. Ultimately, the limitations of the available data lead to the potential for misinterpretation and misunderstanding of seizure freedom outcomes associated with the spectrum of available treatments when examining treatment options for patients. Clearly defined outcome analyses of seizure freedom attainment and duration are essential in future clinical studies of treatment for seizures to guide treatment selection and modification for patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The goal of the study was to measure the performance of academic and private practice (PP) neurologists in detecting interictal epileptiform discharges in routine scalp EEG recordings., Methods: Thirty-five EEG scorers (EEGers) participated (19 academic and 16 PP) and marked the location of ETs in 200 30-second EEG segments using a web-based EEG annotation system. All participants provided board certification status, years of Epilepsy Fellowship Training (EFT), and years in practice. The Persyst P13 automated IED detection algorithm was also run on the EEG segments for comparison., Results: Academic EEGers had an average of 1.66 years of EFT versus 0.50 years of EFT for PP EEGers (P < 0.0001) and had higher rates of board certification. Inter-rater agreement for the 35 EEGers was fair. There was higher performance for EEGers in academics, with at least 1.5 years of EFT, and with American Board of Clinical Neurophysiology and American Board of Psychiatry and Neurology-E specialty board certification. The Persyst P13 algorithm at its default setting (perception value = 0.4) did not perform as well at the EEGers, but at substantially higher perception value settings, the algorithm performed almost as well human experts., Conclusions: Inter-rater agreement among EEGers in both academic and PP settings varies considerably. Practice location, years of EFT, and board certification are associated with significantly higher performance for IED detection in routine scalp EEG. Continued medical education of PP neurologists and neurologists without EFT is needed to improve routine scalp EEG interpretation skills. The performance of automated detection algorithms is approaching that of human experts.

Objective: We evaluated whether deep learning applied to whole-brain presurgical structural connectomes could be used to predict postoperative seizure outcome more accurately than inference from clinical variables in patients with mesial temporal lobe epilepsy (TLE)., Methods: Fifty patients with unilateral TLE were classified either as having persistent disabling seizures (SZ) or becoming seizure-free (SZF) at least 1 year after epilepsy surgery. Their presurgical structural connectomes were reconstructed from whole-brain diffusion tensor imaging. A deep network was trained based on connectome data to classify seizure outcome using 5-fold cross-validation., Results: Classification accuracy of our trained neural network showed positive predictive value (PPV; seizure freedom) of 88 ± 7% and mean negative predictive value (NPV; seizure refractoriness) of 79 ± 8%. Conversely, a classification model based on clinical variables alone yielded <50% accuracy. The specific features that contributed to high accuracy classification of the neural network were located not only in the ipsilateral temporal and extratemporal regions, but also in the contralateral hemisphere., Significance: Deep learning demonstrated to be a powerful statistical approach capable of isolating abnormal individualized patterns from complex datasets to provide a highly accurate prediction of seizure outcomes after surgery. Features involved in this predictive model were both ipsilateral and contralateral to the clinical foci and spanned across limbic and extralimbic networks., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Overview: As new research has increased our understanding of epilepsy and the challenges patients with epilepsy face, the role of the nurse as an educator and advocate has grown. This article, the second in a two-part series, addresses the most important aspects of assessing and caring for patients with epilepsy-highlighting the seizure first-aid instructions that all family members of a patient with epilepsy should have; the teaching points to share with parents of young children with epilepsy; and online epilepsy resources for patients, family members, and health care professionals. The authors also discuss current medical, surgical, neurostimulatory, and dietary approaches to epilepsy treatment.

Overview: Epilepsy is a serious, common neurologic disease that affects people of all ages. As underscored in the 2012 Institute of Medicine report Epilepsy Across the Spectrum: Promoting Health and Understanding, the millions of people living with epilepsy in the United States face the challenges of seeking out high-quality, coordinated health care and community services; overcoming epilepsy misinformation and stigma; and finding understanding and support in their communities. This article, the first in a two-part series, discusses new research that has increased our understanding of epilepsy's etiology and pathophysiology, new definitions that are changing the ways we evaluate and treat this disease, conditions that frequently present with epilepsy, and psychosocial challenges faced by people with epilepsy. Part 2, which will appear in next month's issue, reviews comprehensive nursing care and evidence-based treatment for epilepsy and presents resources for people with epilepsy and their families.

Epilepsy is a common childhood neurologic disorder. In 2007, epilepsy affected an estimated 450,000 children aged 0-17 years in the United States. Approximately 53% of children with epilepsy and special health care needs have co-occurring conditions, and only about one third have access to comprehensive care. The few studies of mortality risk among children with epilepsy as compared with the general population generally find a higher risk for death among children with epilepsy with co-occurring conditions but a similar risk for death among children with epilepsy with no co-occurring conditions. However, samples from these mortality studies are often small, limiting comparisons, and are not representative. This highlights the need for expanded mortality surveillance among children with epilepsy to better understand their excess mortality. This report describes mortality among children with epilepsy in South Carolina during 2000-2011 by demographic characteristics and underlying causes of death. The overall mortality rate among children with epilepsy was 8.8 deaths per 1,000 person-years, and the annual risk for death was 0.84%. Developmental conditions, cardiovascular disorders, and injuries were the most common causes of death among children with epilepsy. Team-based care coordination across medical and nonmedical systems can improve outcomes and reduce health care costs for children with special health care needs, but they require more study among children with epilepsy. Ensuring appropriate and timely health care and social services for children with epilepsy, especially those with complications, might reduce the risk for premature death. Health care providers, social service providers, advocacy groups and others can work together to assess whether coordinated care can improve outcomes for children with epilepsy.

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Computerized detection of epileptiform transients (ETs), characterized by interictal spikes and sharp waves in the EEG, has been a research goal for the last 40 years. A reliable method for detecting ETs would assist physicians in interpretation and improve efficiency in reviewing long-term EEG recordings. Computer algorithms developed thus far for detecting ETs are not as reliable as human experts, primarily due to the large number of false-positive detections. Comparing the performance of different algorithms is difficult because each study uses individual EEG test datasets. In this article, we present EEGnet, a distributed web-based platform for the acquisition and analysis of large-scale training datasets for comparison of different EEG ET detection algorithms. This software allows EEG scorers to log in through the web, mark EEG segments of interest, and categorize segments of interest using a conventional clinical EEG user interface. This software platform was used by seven board-certified academic epileptologists to score 40 short 30-second EEG segments from 40 patients, half containing ETs and half containing artifacts and normal variants. The software performance was adequate. Interrater reliability for marking the location of paroxysmal activity was low. Interrater reliability of marking artifacts and ETs was high and moderate, respectively.

One memory disorder that is potentially treatable with antiepileptic drugs is transient epileptic amnesia (TEA). Working diagnostic consensus criteria for TEA include: (1) a history of recurrent witnessed episodes of transient amnesia; (2) confirmation by a reliable witness that cognitive functions other than memory are intact during typical episodes; and (3) evidence for a diagnosis of epilepsy. We describe a case with both complex partial seizures and episodes of TEA. This is the first reported case of a neurosurgical intervention for symptoms resembling those described in refractory TEA. Video/EEG, 3-T MRI, neuropathology, and neurological as well as neuropsychological findings are presented with postsurgical clinical outcome. The patient underwent right anterior amygdalohippocampectomy for symptoms resembling refractory TEA with additional complex partial seizures at our epilepsy surgical center. She remained seizure free at the 15-month follow-up, and memory complaints remitted. This case report illustrates one memory disorder, transient epileptic amnesia, that is potentially treatable with antiepileptic drugs or surgery., (Published by Elsevier Inc.)

ObjectiveTo describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system.MethodsWe retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection.ResultsWe identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets.SignificanceChronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

ObjectiveTo demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.MethodsRandomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up.ResultsAll 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p

Background and Purpose: This is an observational study to evaluate the safety of magnetic resonance imaging (MRI) to localize subdural grids and depth electrodes in patients with refractory epilepsy using a 1.5 Tesla MR scanner.Methods: We implemented an optimized MRI protocol providing adequate image quality for the assessment of subdural grids and depth electrodes, while minimizing the specific absorption rate (SAR). We reviewed all MRI studies performed in patients with subdural grids and depth electrodes between January 2010 and October 2018. Image quality was graded as acceptable or nonacceptable for the assessment of intracranial device positioning. We reviewed the medical record and any imaging obtained after intracranial implant removal for adverse event or complication occurring during and after the procedure.Results: Ninety-nine patients with refractory epilepsy underwent MRI scans using a magnetization-prepared rapid acquisition of gradient echo sequence and a transmit-receive head coil with depth electrodes and subdural grids in place. Two patients underwent two separate depth electrode implantations for a total of 101 procedures and MRI scans. No clinical adverse events were reported during or immediately after imaging. Image quality was graded as acceptable for 97 MRI scans. Review of follow-up CT and MRI studies after implant removal, available for 70 patients, did not demonstrate unexpected complications in 69 patients.Conclusion: In our experience, a low SAR MRI protocol can be used to safely localize intracranial subdural grids and depth electrode in patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: Incidence of status epilepticus (SE) ranges from 6.8 to 41.0 per 100,000 population. Although SE is associated with significant morbidity and mortality, the temporal relationship between SE, epilepsy, and mortality is less clear. The risk of all-cause mortality following SE with and without prior epilepsy was investigated.Method: This study identified hospitalizations and emergency department visits for persons with SE and persons with epilepsy between 2000 and 2013. Excluded were those with epilepsy subsequent to SE, epilepsia partialis continua, less than 90days follow-up, and less than 2 years of data prior to first diagnosis. The cohort was grouped into: 1) SE only, 2) post-epilepsy SE (PES), and 3) epilepsy only. The risk of mortality was estimated using Cox proportional hazard models adjusting for potential confounders.Results: The cohort (N=82,331) consisted of 1296 SE only cases (1.6%); 2136 PES cases (2.6%); and 78,899 epilepsy only controls (95.8%) with 24.9%, 29.2% and 20.0% mortality, respectively. Compared with controls, the hazard of mortality was increased for those with SE only (hazard ratio [HR]=1.61, 95% CI=1.41-1.82) and PES (HR=1.16, 95% CI=1.07-1.25) after adjustment for demographic and clinical factors. Prior stroke, central nervous system infection, and brain tumor increased the mortality hazard.Conclusion: There is a statistically significant increased risk of all-cause mortality with SE. The risk is stronger in those with no prior epilepsy. Specific etiologies increase mortality risk in those with SE warranting further investigation of the complex associations between these etiologies and SE. [ABSTRACT FROM AUTHOR]

Background: Medial temporal lobe epilepsy (MTLE) is associated with limbic atrophy involving the hippocampus, perihippocampal and extra-temporal structures. While MTLE is related to static structural limbic compromise, it is unknown whether the limbic system undergoes dynamic regional perfusion network alterations during seizures. In this study, we aimed to investigate state specific (i.e. ictal versus interictal) perfusional limbic networks in patients with MTLE. Methods:We studied clinical information and single photon emission computed tomography (SPECT) images obtained with intravenous infusion of the radioactive tracer Technetium- Tc 99 m Hexamethylpropyleneamine Oxime (Tc-99 m HMPAO) during ictal and interictal state confirmed by video-electroencephalography (VEEG) in 20 patients with unilateral MTLE (12 left and 8 right MTLE). Pair-wise voxel-based analyses were used to define global changes in tracer between states. Regional tracer uptake was calculated and state specific adjacency matrices were constructed based on regional correlation of uptake across subjects. Graph theoretical measures were applied to investigate global and regional state specific network reconfigurations. Results: A significant increase in tracer uptake was observed during the ictal state in the medial temporal region, cerebellum, thalamus, insula and putamen. From network analyses, we observed a relative decreased correlation between the epileptogenic temporal region and remaining cortex during the interictal state, followed by a surge of cross-correlated perfusion in epileptogenic temporal-limbic structures during a seizure, corresponding to local network integration. Conclusions: These results suggest that MTLE is associated with a state specific perfusion and possibly functional organization consisting of a surge of limbic cross-correlated tracer uptake during a seizure, with a relative disconnection of the epileptogenic temporal lobe in the interictal period. This pattern of state specific shift in metabolic networks in MTLE may improve the understanding of epileptogenesis and neuropsychological impairments associated with MTLE. [ABSTRACT FROM AUTHOR]

Abstract: Epidemiologic data on convulsive status epilepticus (CSE) is needed to develop preventative strategies. Epilepsy is one of the known risk factors for CSE. A systematic review of epidemiologic studies on status epilepticus (SE) completed in the United States and Europe reports that people with epilepsy account for less than 50% of cases of SE in all age groups. Less is known about the epidemiology of SE in developing countries including those in Central America. A high incidence of epilepsy, widespread non-adherence to anti-epileptic drugs (AED), and common use of complementary and alternative medicines have been shown in all ages in the developing country of Honduras, Central America. In 2003, an epidemiologic study of CSE in Honduran children demonstrated it is common and exhibits a long duration until onset of treatment. The etiologies, treatment, and outcomes of CSE in Honduran adults have not been thoroughly studied. This study is a consecutive case series of 31 adult patients presenting with CSE to the adult medicine emergency department of the tertiary care “Hospital Escuela” in the capital city Tegucigalpa, Honduras. The majority (77.4%) of patients had a prior history of epilepsy. Non-adherence to AED was the most common etiology of CSE (75.0%). The mortality rate in this pilot CSE study was 14.8%, which is similar to studies from industrialized countries where mortality from status epilepticus ranged from 7.6 to 22% for all age groups. However, this rate is concerning given that CSE from epilepsy and AED non-adherence generally carries a good prognosis. Improving AED adherence in this population appears to be the most effective approach in decreasing the rate, and possibly the mortality of Honduran adult CSE. [Copyright &y& Elsevier]

Purpose: Medial temporal epilepsy (MTLE) is associated with extrahippocampal brain atrophy. The mechanisms underlying brain damage in MTLE are unknown. Seizures may lead to neuronal damage, but another possible explanation is deafferentation from loss of hippocampal connections. This study aimed to investigate the relationship between hippocampal deafferentation and brain atrophy in MTLE. Methods: Three different MRI studies were performed involving 23 patients with unilateral MTLE (8 left and 15 right) and 34 healthy controls: (1) voxel-based morphometry (VBM), (2) diffusion tensor imaging (DTI) and (3) probabilistic tractography (PT). VBM was employed to define differences in regional gray matter volume (GMV) between controls and patients. Voxel-wise analyses of DTI evaluated differences in fractional anisotropy (FA), mean diffusivity (MD) and hippocampal PT. Z-scores were computed for regions-of-interest (ROI) GMV and peri-hippocampal FA and MD (to quantify hippocampal fiber integrity). The relationship between hippocampal deafferentation and regional GMV was investigated through the association between ROI Z scores and hippocampal fiber integrity. Results: Patients with MTLE exhibited a significant reduction in GMV and FA in perihippocampal and limbic areas. There was a decrease in hippocampal PT in patients with MTLE in limbic areas. A significant relationship between loss of hippocampal connections and regional GMV atrophy was found involving the putamen, pallidum, middle and inferior temporal areas, amygdala and ceberellar hemisphere. Discussion: There is a relationship between hippocampal disconnection and regional brain atrophy in MTLE. These results indicate that hippocampal deafferentation plays a contributory role in extrahippocampal brain damage in MTLE. [ABSTRACT FROM AUTHOR]

Purpose: To describe the effects of vagus nerve stimulation (VNS) on sleep-related breathing in a sample of 16 epilepsy patients. Methods: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21-58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial. Results: Baseline PSGs: One of 16 patients had an apneahypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on-time) than without VNS activation (off-time; p = 0.016). Follow-up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels. Conclusions: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained < 5 in the majority of patients and was only mildly elevated (< 12) in five patients. In one patient, CPAP resolved VNS-related respiratory events. [ABSTRACT FROM AUTHOR]

Abstract: Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story–Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we evaluate the diagnostic and localizing value of SPECT in three patients with nonconvulsive status epilepticus (NCSE). Our results indicate that ictal/subtraction ictal SPECT is a useful complementary noninvasive diagnostic test in patients with focal NCSE. This is especially the case when the EEG findings are inconclusive and for patients in whom surgical treatment is being considered. [Copyright &y& Elsevier]