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Stereotactic electroencephalography (SEEG) is an increasingly utilized method for invasive monitoring in patients with medically intractable epilepsy. Yet, the lack of standardization for labeling electrodes hinders communication among clinicians. A rational clustering of contacts based on anatomy rather than arbitrary physical leads may help clinical neurophysiologists interpret seizure networks. We identified SEEG electrodes on post-implant CTs and registered them to preoperative MRIs segmented according to an anatomical atlas. Individual contacts were automatically assigned to anatomical areas independent of lead. These contacts were then organized using a hierarchical anatomical schema for display and interpretation. Bipolar-referenced signal cross-correlations were used to compare the similarity of grouped signals within a conventional montage versus this anatomical montage. As a result, we developed a hierarchical organization for SEEG contacts using well-accepted, free software that is based solely on their post-implant anatomical location. When applied to three example SEEG cases for epilepsy, clusters of contacts that were anatomically related collapsed into standardized groups. Qualitatively, seizure events organized using this framework were better visually clustered compared to conventional schemes. Quantitatively, signals grouped by anatomical region were more similar to each other than electrode-based groups as measured by Pearson correlation. Further, we uploaded visualizations of SEEG reconstructions into the electronic medical record, rendering them durably useful given the interpretable electrode labels. In conclusion, we demonstrate a standardized, anatomically grounded approach to the organization of SEEG neuroimaging and electrophysiology data that may enable improved communication among and across surgical epilepsy teams and promote a clearer view of individual seizure networks.

OBJECTIVE Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, they are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus. We hypothesized that a two-trajectory approach could improve ablation of all relevant MTL structures. First, we created large-scale computer simulations to compare idealized one- vs two-trajectory approaches. A two-trajectory approach was then validated in an initial cohort of patients. METHODS We used magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two-trajectory LITT; demographic, operative, and outcome data were collected. RESULTS The two-trajectory approach was superior to the one-trajectory approach at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p

BACKGROUND Patients with refractory, bilateral, multifocal epilepsy have few treatment options that typically include a combination of antiseizure medications (ASMs) and vagus nerve stimulation (VNS). A man in his 40s presented with epilepsy refractory to a combination of five ASMs plus VNS; he was still experiencing 7–10 seizures per week. His seizure network involved multiple foci in both frontal and temporal lobes. Bilateral depth electrodes were implanted into the centromedian/parafascicular (CM/PF) complex of the thalamus and connected to the responsive neurostimulation (RNS) system for closed-loop stimulation and neurophysiological monitoring. OBSERVATIONS The patient reported clear improvement in his seizures since the procedure, with a markedly reduced number of seizures and decreased seizure intensity. He also reported stretches of seizure freedom not typical of his preoperative baseline, and his remaining seizures were milder, more often with preserved awareness. Generalized seizures with loss of consciousness have decreased to about one per month. RNS data confirmed a right-sided predominance of the bilateral seizure onsets. LESSONS In this patient with multifocal, bilateral frontotemporal epilepsy, RNS of the CM/PF thalamic complex combined with VNS was found to be beneficial. The RNS device was able to detect seizures propagating through the thalamus, and stimulation produced a decrease in seizure burden and intensity.

Background and purpose The aim of this study was to evaluate the quality of smartphone videos (SVs) of neurologic events in adult epilepsy outpatients. The use of home video recording in patients with neurological disease states is increasing. Experts interpretation of outpatient smartphone videos of seizures and neurological events has demonstrated similar diagnostic accuracy to inpatient video-electroencephalography (EEG) monitoring. Methods A prospective, multicenter cohort study was conducted to evaluate SV quality in patients with paroxysmal neurologic events from August 15, 2015 through August 31, 2018. Epileptic seizures (ESs), psychogenic nonepileptic attacks (PNEAs), and physiologic nonepileptic events (PhysNEEs) were confirmed by video-EEG monitoring. Experts and senior neurology residents blindly viewed cloud-based SVs without clinical information. Quality ratings with regard to technical and operator-driven metrics were provided in responses to a survey. Results Forty-four patients (31 women, age 45.1 years [r = 20-82]) were included and 530 SVs were viewed by a mean of seven experts and six residents; one video per patient was reviewed for a mean of 133.8 s (r = 9-543). In all, 30 patients had PNEAs, 11 had ESs, and three had PhysNEEs. Quality was suitable in 70.8% of SVs (375/530 total views), with 36/44 (81.8%) patient SVs rated as adequate by the majority of reviewers. Accuracy improved with the presence of convulsive features from 72.4% to 98.2% in ESs and from 71.1% to 95.7% in PNEAs. An accurate diagnosis was given by all reviewers (100%) in 11/44 SVs (all PNEAs). Audio was rated as good by 86.2% of reviewers for these SVs compared with 75.4% for the remaining SVs (p = 0.01). Lighting was better in SVs associated with high accuracy (p = 0.06), but clarity was not (p = 0.59). Poor video quality yielded unknown diagnoses in 24.2% of the SVs reviewed. Features hindering diagnosis were limited interactivity, restricted field of view and short video duration. Conclusions Smartphone video quality is adequate for clinical interpretation in the majority of patients with paroxysmal neurologic events. Quality can be optimized by encouraging interactivity with the patient, adequate duration of the SV, and enlarged field of view during videography. Quality limitations were primarily operational though accuracy remained for SV review of ESs and PNEAs.

Inhibitory neurons are critical for normal brain function but dysregulated in disorders such as epilepsy. At least two theories exist for how inhibition may acutely decrease during a seizure: hyperpolarization of fast-spiking (FS) inhibitory neurons by other inhibitory neurons, or depolarization block (DB) of FS neurons resulting in an inability to fire action potentials. Firing rate alone is unable to disambiguate these alternatives. Here, we show that human FS neurons can stop firing due to both hyperpolarization and DB within the same seizure. However, only DB of FS cells is associated with dramatic increases in local seizure amplitude, unobstructed traveling waves, and transient increases in excitatory neuronal firing. This result is independent of seizure etiology or focus. Computational models of DB reproduce the in vivo human biophysics. These methods enable intracellular decoding using only extracellular recordings in humans and explain the otherwise ambiguous inhibitory neuronal control of human seizures.

Rationale White matter abnormalities occur in both temporal lobe epilepsy (TLE) and depression, but there is limited research examining the depression–white matter association in depressed individuals with TLE. This study examined the relationship between white matter integrity (WMI) and depression including the influence of age at seizure onset, in adults with TLE, TLE and depression, and depression only. Methods Thirty-one adults were in one of three groups: TLE without depression (TLE; n = 11), TLE with depression (TLE + DEP; n = 9), and depression without TLE (DEP; n = 11). Participants completed structured interviews for depression diagnosis and severity. White matter integrity was estimated based on fractional anisotropy (FA) calculated in frontotemporolimbic (FTL) and non-FTL regions in the JHU DTI atlas. Results In adults with TLE (n = 20), depressive symptomology was significantly correlated with FA in non-FTL regions and trended toward significance in FTL regions. These associations were found in FTL (statistically significant) and non-FTL (trended toward significance) regions in participants with childhood seizure onset but not in those with adolescent/adult seizure onset. Conclusions Current results suggest that WMI, within FTL and non-FTL regions, are associated with depressive symptomology in adults with TLE. This association may be most notable in those with childhood-onset epilepsy. These findings could have important implications for the conceptualization and clinical care of neuropsychiatric comorbidities in TLE.

Differentiating epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) is commonly based on electroencephalogram and concurrent video recordings (vEEG). Here, we demonstrate that these two types of seizures can be discriminated based on signals related to autonomic nervous system activity recorded via wearable sensors. We used Empatica E4 Wristband sensors worn on both arms in vEEG confirmed seizures, and machine learning methods to train classifiers, specifically, extreme gradient boosting (XGBoost). Classification performance achieved a predictive accuracy of 78 ± 1.5% on previously unseen data for whether a seizure was epileptic or psychogenic, which is 6 standard deviations above the baseline of 68% accuracy. Our dataset contained altogether 35 seizures from 18 patients out of which 8 patients had 13 convulsive seizures. Prediction of seizure type was based on simple features derived from the segments of autonomic activity measurements (electrodermal activity, body temperature, blood volume pulse, and heart rate) and forearm acceleration. Features related to heart rate and electrodermal activity were ranked as the top predictors in XGBoost classifiers. We found that patients with PNES had a higher ictal heart rate and electrodermal activity than patients with ES. In contrast to existing published studies of mainly convulsive seizures, our classifier focuses on autonomic signals to differentiate convulsive or nonconvulsive semiology ES from PNES. Our results show that autonomic activity recorded via wearable sensors provides promising signals for detection and discrimination of psychogenic and epileptic seizures, but more work is necessary to improve the predictive power of the model.

Objective The objective of the study was to localize sources of interictal high-frequency activity (HFA), from tripolar electroencephalography (tEEG), in patient-specific, realistic head models. Methods Concurrent electroencephalogram (EEG) and tEEG were recorded from nine patients undergoing video-EEG, of which eight had seizures during the recordings and the other had epileptic activity. Patient-specific, realistic boundary element head models were generated from the patient's magnetic resonance images (MRIs). Forward and inverse modeling was performed to localize the HFA to cortical surfaces. Results In the present study, performed on nine patients with epilepsy, HFA observed in the tEEG was localized to the surface of subject-specific, realistic, cortical models, and found to occur almost exclusively in the seizure onset zone (SOZ)/irritative zone (IZ). Significance High-frequency oscillations (HFOs) have been studied as precise biomarkers of the SOZ in epilepsy and have resulted in good therapeutic effect in surgical candidates. Knowing where the sources of these highly focal events are located in the brain can help with diagnosis. High-frequency oscillations are not commonly observed in noninvasive EEG recordings, and invasive electrocorticography (ECoG) is usually required to detect them. However, tEEG, i.e., EEG recorded on the scalp with tripolar concentric ring electrodes (TCREs), has been found to detect narrowband HFA from high gamma (approximately 80 Hz) to almost 400 Hz that correlates with SOZ diagnosis. Thus, source localization of HFA in tEEG may help clinicians identify brain regions of the epileptic zone. At the least, the tEEG HFA localization may help determine where to perform intracranial recordings used for precise diagnosis.

Importance Misdiagnosis of epilepsy is common. Video electroencephalogram provides a definitive diagnosis but is impractical for many patients referred for evaluation of epilepsy. Objective To evaluate the accuracy of outpatient smartphone videos in epilepsy. Design, Setting, and Participants This prospective, masked, diagnostic accuracy study (the OSmartViE study) took place between August 31, 2015, and August 31, 2018, at 8 academic epilepsy centers in the United States and included a convenience sample of 44 nonconsecutive outpatients who volunteered a smartphone video during evaluation and subsequently underwent video electroencephalogram monitoring. Three epileptologists uploaded videos for physicians from the 8 epilepsy centers to review. Main Outcomes and Measures Measures of performance (accuracy, sensitivity, specificity, positive predictive value, and negative predictive value) for smartphone video–based diagnosis by experts and trainees (the index test) were compared with those for history and physical examination and video electroencephalogram monitoring (the reference standard). Results Forty-four eligible epilepsy clinic outpatients (31 women [70.5%]; mean [range] age, 45.1 [20-82] years) submitted smartphone videos (530 total physician reviews). Final video electroencephalogram diagnoses included 11 epileptic seizures, 30 psychogenic nonepileptic attacks, and 3 physiologic nonepileptic events. Expert interpretation of a smartphone video was accurate in predicting a video electroencephalogram monitoring diagnosis of epileptic seizures 89.1% (95% CI, 84.2%-92.9%) of the time, with a specificity of 93.3% (95% CI, 88.3%-96.6%). Resident responses were less accurate for all metrics involving epileptic seizures and psychogenic nonepileptic attacks, despite greater confidence. Motor signs during events increased accuracy. One-fourth of the smartphone videos were correctly diagnosed by 100% of the reviewing physicians, composed solely of psychogenic attacks. When histories and physical examination results were combined with smartphone videos, correct diagnoses rose from 78.6% to 95.2%. The odds of receiving a correct diagnosis were 5.45 times greater using smartphone video alongside patient history and physical examination results than with history and physical examination alone (95% CI, 1.01-54.3;P = .02). Conclusions and Relevance Outpatient smartphone video review by experts has predictive and additive value for diagnosing epileptic seizures. Smartphone videos may reliably aid psychogenic nonepileptic attacks diagnosis for some people.

While antiepileptic drugs (AEDs) provide adequate seizure control for most patients with epilepsy, ~30% continue to have seizures despite treatment with two or more AEDs.1 In addition to direct harm from seizures, poor epilepsy control correlates with higher mortality, morbidity, 2, 3 and cost to the healthcare system.4 In the subset of patients with persistent seizures despite medical management, surgical intervention and neuromodulation may be more effective. Primary care physicians and general neurologists should be aware of non-AED treatment options that are standard of care for drug- resistant epilepsy (DRE).

SummaryObjective New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Methods Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic–clonic seizures and 49 focal to bilateral tonic–clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. Results The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had

Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (∼40–60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ∼3 Hz). Fine (

Epilepsy is the second most prevalent neurological disorder (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}\(\sim 1\) \end{document}% prevalence) affecting \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}\(\sim 67\) \end{document} million people worldwide with up to 75% from developing countries. The conventional electroencephalogram is plagued with artifacts from movements, muscles, and other sources. Tripolar concentric ring electrodes automatically attenuate muscle artifacts and provide improved signal quality. We performed basic experiments in healthy humans to show that tripolar concentric ring electrodes can indeed record the physiological alpha waves while eyes are closed. We then conducted concurrent recordings with conventional disc electrodes and tripolar concentric ring electrodes from patients with epilepsy. We found that we could detect high frequency oscillations, a marker for early seizure development and epileptogenic zone, on the scalp surface that appeared to become more narrow-band just prior to seizures. High frequency oscillations preceding seizures were present in an average of 35.5% of tripolar concentric ring electrode data channels for all the patients with epilepsy whose seizures were recorded and absent in the corresponding conventional disc electrode data. An average of 78.2% of channels that contained high frequency oscillations were within the seizure onset or irritative zones determined independently by three epileptologists based on conventional disc electrode data and videos., Electroencephalography (EEG) is a noninvasive means for recording electrical activity of the brain. We have developed tripolar concentric ring electrodes (TCREs) and have shown that TCREs provide higher signal-to-noise ratios, higher spatial resolution, and less mutual information than conventional disc electrodes. This paper describes the results of a clinical study of patients with epilepsy to determine if high-frequency oscillations (HFOs) were present in EEG recorded with TCREs.

This study examined the contribution of depression to reduced executive functioning in temporal lobe epilepsy (TLE) using three groups: TLE only (TLE; N=29), TLE+depression (TLE+DEP) (N=22), and nonneurologic participants with depression (DEP; N=31). Participants completed the Delis-Kaplan Executive Function System. Individuals with TLE performed worse than the DEP group on many tests of executive functions. Among the TLE participants, those with depression demonstrated poorer executive functioning. These findings support the notion that depression may further contribute to executive difficulties in individuals with TLE. Depression treatment in this population could lead to improvements in cognition.

We examined if depression symptoms in patients with intractable (IE) or controlled epilepsy (CE) differ and how long after onset of epilepsy these effects would be most pronounced. The NDDI-E was administered to all outpatients (n=358) seen in a comprehensive epilepsy program clinic over a two-year period. Patients who met inclusion criteria (n=223) completed a total of 431 NDDI-E surveys over this time. Patients with a diagnosis of IE (n=72) or CE (n=151) were compared as a function of time since their epilepsy onset, segmented into 10-year epochs. Depression symptoms were higher in patients with IE compared to CE at 10

This study used the Bear-Fedio Personality Inventory (BFI) to compare 41 individuals with temporal lobe epilepsy (TLE) and 37 with psychogenic non-epileptic seizures (NES). Both groups exhibited similar elevations on the BFI, although TLE individuals show greater endorsement of at least one hypergraphia symptom, as compared with those with NES. The correlates of the BFI with demographic and seizure characteristics differed between the groups. These results argue against a specific TLE personality syndrome and suggest that personality characteristics may be related to the experience of having repeated seizures, rather than the specific underlying pathophysiology of temporal lobe epilepsy.

Several studies have shown reliable predictive factors for outcome in status epilepticus (SE), especially etiology and presentation in coma. Duration of SE is predictive, but probably only in the first few hours, and there have been many reports of patients treated successfully for SE lasting many days or weeks. Nevertheless, there are many other patients with SE treated for prolonged periods without success, sometimes apparently futilely. We compared clinical features of 10 survivors of prolonged SE with those of a matched cohort treated for similarly prolonged episodes but unsuccessfully, looking for exceptions to known predictive factors. Multiple medical problems (i.e., etiologies) and coma on presentation were confirmed as predictors of a poor outcome. Analysis of individual exceptions to these predictors showed that age, overall background health, and family input on the value of prolonged treatment, on the one hand, and earlier epilepsy plus rapid and accurate diagnosis and treatment, on the other, contributed to results different from what would have been expected.

Cardiac computed tomographic angiography (CCTA) is a unique diagnostic modality that can provide a comprehensive assessment of cardiac anatomy. Rapid advances in scanner and software technology have resulted in the ability to noninvasively image the coronary arteries. However, careful patient preparation and scanning technique is required to ensure optimal image quality while minimizing radiation dose delivered. Important components of patient preparation include knowledge of the indications and contraindications for CCTA, patient screening, patient premedication, patient positioning, prescan instruction, and electrocardiograph lead placement. Scanning technique should be determined on a patient by patient basis and tailored according to age and radiation risk, body mass index and chest circumference, heart rate and variability, presence of stents, and coronary calcification.

To determine whether 1) combined oral contraceptive (COC) use affects serum levels of valproate (VPA) as well as lamotrigine (LTG) and 2) the naturally occurring high (mid-luteal) and low (early-mid follicular) reproductive steroid level phases of the menstrual cycle might affect antiepileptic drug levels as well.This investigation compared serum antiepileptic drug levels at two timepoints during a single menstrual cycle in four groups of women with epilepsy: 12 on VPA, 12 on VPA plus COC (VPA-COC), 12 on LTG, and 12 on LTG plus COC (LTG-COC).Both VPA and LTG levels were lower (p0.01) on active COC than on inactive pill with median declines of 23.4% for the VPA-COC group and 32.6% for the LTG-COC group. Serum LTG levels showed a notable but not significant 31.3% median decline during the mid-luteal phase compared to the early-mid follicular phase in the non-COC group. The non-COC valproate group showed the least change of any group between the two measured timepoints with a decline of 8.3% (p = NS).The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle.

Status epilepticus (SE) is not rare in critically ill intensive care unit (ICU) patients, but its diagnosis is often delayed or missed, in part because it is mistaken for other causes of altered mental status. Even once diagnosed, SE in the ICU can be refractory to treatment. We sought to determine the causes, clinical features, and difficulties in diagnosis of SE in the ICU, and the effects of antiepileptic drugs (AEDs) on its course. We reviewed the course of ICU patients with both clinical and EEG evidence of SE, attempting to determine which patients are at risk for unsuspected SE, what was the typical delay in diagnosis, and whether AED treatment made a difference in their clinical courses. By clinical and EEG evidence, 91 ICU patients with SE were identified, all with abnormal mental status: 74 were comatose. Vascular disease (in 24) and anoxia (22) were the most common causes; most had multiple medical problems. Although 76 patients had clinically evident seizures earlier (and 56, clinical SE) only 20 were thought to be in SE at the time of the diagnostic EEG. There was a median delay of 48 hours from clinical deterioration until diagnosis in patients with earlier clinical seizures and 72 hours without seizures. Among the 68 nonanoxic patients treated with AEDs, 38 (56%) seemed to improve in alertness, including 25 who were comatose. Although patients who were stuporous or confused (vs. comatose) improved more often on AEDs, they were less often realized to be in SE before the EEG. Patients with earlier seizures were also more likely to improve, but no more likely to be diagnosed before the EEG. Patients who responded to AEDs were more likely to survive. ICU patients with altered mental status and EEG evidence of SE often have severe medical and surgical illnesses, refractory SE, and a high mortality. The delay to diagnosis is substantial, but a significant subset of patients improves on AEDs once SE is discovered. This diagnosis should be sought more often in ICU patients with abnormal mental status, especially after clinical seizures or SE without full recovery.

This chapter describes the evaluation process for the diagnosis of psychogenic nonepileptic seizures (PNES), which is determined based on concordance of the composite evidence available, including historic and physical exam findings, seizure semiology, and ictal/interictal electroencephalogram (EEG). No single clinical feature is pathognomonic of PNES. The diagnosis of PNES can be at times challenging, such as when seizure documentation on video-EEG cannot be readily achieved. A multicomponent approach to the diagnosis of PNES, with use of all available evidence, may facilitate diagnosis and then care of patients with PNES. Emerging evidence supports the use of symptom identification by the patient as part of the treatment of these patients. With advances in diagnostic methods and criteria, the diagnosis of PNES can be made reliably.

A 39-year-old man, who presented at age 3 1 2 with Landau–Kleffner syndrome, had persisting oral and written language deficits into adulthood. Seizures were easily controlled in childhood, but reemerged in adulthood as medication-refractory complex partial seizures. Abnormal T2 signal hyperintensity was seen in the left mesial temporal area on brain MRI. Later, left temporal lobectomy revealed focal cortical dysplasia in the lateral temporal neocortex and gliosis plus neuronal loss in the hippocampus. This case suggests that focal cortical microdysgenesis may be a cause of the Landau–Kleffner syndrome. Persistent seizures in this illustrative case may have led to the evolution of dual-temporal-lobe pathology with mesial temporal sclerosis.

International audience; Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4 × 4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) a newly developed stage segmentation method, applied to local field potentials (LFPs) and multiunit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~ 2–3 Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25–60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA peak onset time (in seizures where such peak onset occurred) and changes in MUA or LFP propagation patterns. Overall, our findings indicate that the recruitment of neocortical territories into ictal activity undergoes complex spatiotemporal dynamics evolving in slow discrete states, which are consistent across seizures within each patient. Furthermore, ictal states at finer spatiotemporal scales (individual SWDs or gamma oscillations) are organized by slower time scale network dynamics evolving through these discrete stages.

Memory complaints are common among older adults with epilepsy (OAE), though discrepancy between subjective complaints and objective performance often exists. This study examined how accurately OAE and their informants reported on the participant's cognitive difficulties by comparing ratings of everyday cognition to objective performance. Thirty-seven OAE and 27 older adult controls completed a brief battery of neuropsychological tests, the Beck Depression Inventory, and the Cognitive Difficulties Scale (CDS). Each participant had an informant who completed the CDS. Older adults with epilepsy performed worse than controls on cognitive testing and reported more subjective cognitive complaints. Neither participant- nor informant-reported cognitive complaints were related to performance on any of the neuropsychological tests for either the group with epilepsy or control group, but both were related to greater depressive symptoms. Results suggest that subjective report of cognitive problems by both OAE and their informants may not reliably reflect the extent to which these problems exist.

The relationship between peripheral arterial disease (PAD), cardiovascular disease (CAD), and underlying atherosclerotic risk factors such as dyslipidemia, smoking, diabetes, and hypertension is well established. Patients with PAD have dramatically increased risks of cardiovascular mortality due to underlying atherosclerosis. As interventionalists, we focus primarily on improving the functional status of our patients by "fixing" their peripheral arterial occlusions, often ignoring the more serious concerns, as well as the root cause of the problem. In addition to interventional strategies, comprehensive clinical management of PAD should include attention to risk factor modification, lifestyle changes, exercise therapy, and pharmacologic interventions. Conventional training in interventional radiology imparts very little familiarity with these management issues. The following article addresses one critical modifiable risk factor, dyslipidemia, and treatment with the powerful class of drugs, the statins, reviewing the rationale for as well as the practical considerations in the use of these agents.

Importance There is a paucity of controlled treatment trials for the treatment of conversion disorder, seizures type, also known as psychogenic nonepileptic seizures (PNES). Psychogenic nonepileptic seizures, the most common conversion disorder, are as disabling as epilepsy and are not adequately addressed or treated by mental health clinicians. Objective To evaluate different PNES treatments compared with standard medical care (treatment as usual). Design, Setting, and Participants Pilot randomized clinical trial at 3 academic medical centers with mental health clinicians trained to administer psychotherapy or psychopharmacology to outpatients with PNES. Thirty-eight participants were randomized in a blocked schedule among 3 sites to 1 of 4 treatment arms and were followed up for 16 weeks between September 2008 and February 2012; 34 were included in the analysis. Interventions Medication (flexible-dose sertraline hydrochloride) only, cognitive behavioral therapy informed psychotherapy (CBT-ip) only, CBT-ip with medication (sertraline), or treatment as usual. Main Outcomes and Measures Seizure frequency was the primary outcome; psychosocial and functioning measures, including psychiatric symptoms, social interactions, quality of life, and global functioning, were secondary outcomes. Data were collected prospectively, weekly, and with baseline, week 2, midpoint (week 8), and exit (week 16) batteries. Within-group analyses for each arm were performed on primary (seizure frequency) and secondary outcomes from treatment-blinded raters using an intention-to-treat analysis. Results The psychotherapy (CBT-ip) arm showed a 51.4% seizure reduction ( P = .01) and significant improvement from baseline in secondary measures including depression, anxiety, quality of life, and global functioning ( P P = .008) and significant improvements in some secondary measures, including global functioning ( P = .007). The sertraline-only arm did not show a reduction in seizures ( P = .08). The treatment as usual group showed no significant seizure reduction or improvement in secondary outcome measures ( P = .19). Conclusions and Relevance This pilot randomized clinical trial for PNES revealed significant seizure reduction and improved comorbid symptoms and global functioning with CBT-ip for PNES without and with sertraline. There were no improvements in the sertraline-only or treatment-as-usual arms. This study supports the use of manualized psychotherapy for PNES and successful training of mental health clinicians in the treatment. Future studies could assess larger-scale intervention dissemination. Trial Registration clinicaltrials.gov Identifier:NCT00835627

PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.

The ability to trigger functional magnetic resonance imaging (fMRI) acquisitions related to the occurrence of EEG-based physiologic transients has changed the field of fMRI into a more dynamically based technique. By knowing the temporal relationship between focal increases in neuronal firing rates and the provoked focal increase in blood flow, investigators are able to maximize the fMR-linked images that show where the activity originates. Our mastery of recording EEG inside the bore of a MR scanner has also allowed us to develop cognitive paradigms that record not only the fMR BOLD images, but also the evoked potentials (EPs). The EPs can subsequently be subjected to localization paradigms that can be compared to the localization seen on the BOLD images. These two techniques will most probably be complimentary. BOLD responses are dependent on a focal increase in metabolic demand while the EPs may or may not be related to energy demand increases. Additionally, recording EPs require that the source or sources of that potential come from an area that is able to generate far-field potentials. These potentials are related to the laminar organization of the neuronal population generating that potential. As best we know the BOLD response does not depend on any inherent laminar neuronal organization. Therefore, by merging these two recording methods, it is likely that we will gain a more detailed understanding of not only the areas involved in certain physiologic events, e.g. focal epilepsy or cognitive processing, but also on the sequencing of the activation of the various participating regions.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool for patients with intractable epilepsy. Although seizures during treatment have been reported as adverse events in some patients, the nature and severity of seizures that may be provoked by low-frequency rTMS in patients with epilepsy have not been extensively studied. Accordingly, this article documents seizures in patients (n = 5) with intractable epilepsy and average seizure frequency greater than one per day who underwent 1-Hz rTMS for seizure suppression. We report three observations in the present case series: (1) in each instance the in-session seizure was typical in semiology to the patient’s habitual seizures, (2) the duration of each documented seizure was either the same as or shorter than the patients’ baseline seizures, and (3) the overall neurological outcome on follow-up was not affected by the in-session seizures. More data will be required for valid conclusions with respect to safety and tolerability of low-frequency rTMS in patients with epilepsy, but it is noteworthy from our perspective that seizures during rTMS in this series were similar to the patients’ habitual seizures, occurred in patients with epilepsy with baseline seizure frequency exceeding one per day, and did not correlate with a poor neurological outcome or with absence of clinical response to rTMS.

Elevations in temperature may produce conduction block in demyelinated neurons. A well-described phenomenon in multiple sclerosis, it has also been reported in some patients with inflammatory demyelinating polyneuropathies. We used carpal tunnel syndrome (CTS) as a model to study the effect of heat on nerves with focal demyelination secondary to chronic compression. Compound motor and sensory responses were measured in 12 CTS patients and 12 normal subjects at 32 degrees C and with heating to 42 degrees C. Changes in relative motor response amplitude and area were similar for both normal subjects and CTS patients. In CTS patients, however, sensory response amplitude and area decreased 34.3% and 48.9%, significantly more than the 25.2% and 39.1% reductions in normal subjects (P=0.021 and P=0.018 respectively). We hypothesize that these reductions in response amplitude are secondary to the occurrence of heat-induced conduction block in demyelinated sensory neurons.

Physicians in Rhode Island sometimes find it difficult to advise patients about returning to driving after they present with a seizure or syncopal episode due to lack of statutory or professional guidance on the issue. We provide an overview of the medical literature on public policies and recommendations regarding driving after seizures or syncope. We also present the laws in Rhode Island regarding physician notification of the medical advisory board of the Department of Motor Vehicles, legal obligations, and immunity from prosecution for those who report. Finally, we present the results of a survey of current practice by Rhode Island neurologists when they advise patients who have had a recent seizure or unexplained syncopal event. Based upon this information, we hope local practitioners are empowered in their decision making on driving restrictions and we hope this data informs future public policy efforts.

Epilepsy incidence is higher in the elderly than in younger adults. Diagnosis and management of the elderly with epilepsy presents several specific demands. A variety of other mimics can confound the diagnosis in this age group. Treatment choices should consider issues of metabolism, co-morbidities, and side effect profiles. Drug-drug interactions are prevalent and need to be minimized and/ or anticipated.

To evaluate different contributions of aspects of family functioning (FF) on health-related quality of life (HRQOL) in patients with psychogenic nonepileptic seizures (PNES) versus epileptic seizures (ES).Forty-five participants with PNES and 32 with ES completed self-report measures of FF (Family Assessment Device; FAD), HRQOL (Quality of Life in Epilepsy-31), and depression (Beck Depression Inventory-II; BDI-II). The FAD is a self-report questionnaire that assesses FF along six dimensions and general functioning. Regression analyses were used to evaluate the contribution of FF to HRQOL above and beyond the effects of disease severity and depression.Mean Family General Functioning fell in the unhealthy range in participants with ES or PNES. On further analysis, male participants in each group endorsed unhealthy levels of FF compared to female participants. Patients with PNES reported poorer HRQOL and greater depressive symptoms compared to ES participants; there were no gender differences in HRQOL. Regression analyses indicated that the FAD Roles subscale predicted reduced HRQOL in patients with PNES after controlling for illness duration, seizure frequency, and depression. After controlling for the same factors, Communication and Affective Involvement subscales scores predicted HRQOL in ES participants.Family dysfunction was reported in both ES and PNES participants, but greater family dysfunction was experienced by male participants in both groups. Aspects of FF predicted HRQOL in patients with PNES and ES differentially. FF may be an important treatment target to enhance coping in these groups, although the treatments may need to target different aspects of FF in PNES versus ES.

Summary Purpose: To evaluate different contributions of aspects of family functioning (FF) on health-related quality of life (HRQOL) in patients with psychogenic nonepileptic seizures (PNES) versus epileptic seizures (ES). Methods: Forty-five participants with PNES and 32 with ES completed self-report measures of FF (Family Assessment Device; FAD), HRQOL (Quality of Life in Epilepsy-31), and depression (Beck Depression Inventory-II; BDI-II). The FAD is a self-report questionnaire that assesses FF along six dimensions and general functioning. Regression analyses were used to evaluate the contribution of FF to HRQOL above and beyond the effects of disease severity and depression. Key Findings: Mean Family General Functioning fell in the unhealthy range in participants with ES or PNES. On further analysis, male participants in each group endorsed unhealthy levels of FF compared to female participants. Patients with PNES reported poorer HRQOL and greater depressive symptoms compared to ES participants; there were no gender differences in HRQOL. Regression analyses indicated that the FAD Roles subscale predicted reduced HRQOL in patients with PNES after controlling for illness duration, seizure frequency, and depression. After controlling for the same factors, Communication and Affective Involvement subscales scores predicted HRQOL in ES participants. Significance: Family dysfunction was reported in both ES and PNES participants, but greater family dysfunction was experienced by male participants in both groups. Aspects of FF predicted HRQOL in patients with PNES and ES differentially. FF may be an important treatment target to enhance coping in these groups, although the treatments may need to target different aspects of FF in PNES versus ES.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized ­pathologically by large numbers of extracellular neuritic plaques containing a core of amyloid Aβ fibrils as well as intracellular neurofibrillary tangles containing hyperphosphorylated tau protein filaments in the neurons of the cerebral cortex. Other features include reactive gliosis, synaptic loss, neuronal death, and mitochondrial dysfunction. A small percentage of cases are due to genetic mutations of the amyloid precursor gene on chromosome 21 and mutations in presenilin 1 and 2 genes on chromosomes 2 and 14, respectively [1]. These presenilin proteins are inherent to secretase enzymes involved with cleavage of the amyloid Aβ precursor protein into amyloidogenic A fragments, particularly Aβ42 [2]. Apolipoprotein E4 is an important risk factor allele for other cases [3]. The molecular underpinnings for the common form of AD occurring sporadically in older patients remain largely to be elucidated.

Neurotrophins promote neurogenesis and help regulate synaptic reorganization. Their dysregulation has been implicated in a number of neurologic and psychiatric disorders. Previous studies have shown decreased levels of brain-derived neurotrophic factor (BDNF) in the serum of patients with psychiatric disorders such as major depressive disorder (MDD) and conversion disorder (CD). In human patients with temporal lobe epilepsy, there is an increase in both BDNF mRNA and protein levels in surgically resected hippocampi compared to controls. One study of children with epilepsy has found normal to increased serum BDNF levels compared to controls. Plasma [corrected] BDNF levels have not been investigated in adult patients with epileptic seizures (ES). We hypothesized that BDNF would differentiate between ES and psychogenic nonepileptic seizures (PNES).We assessed plasma [corrected] BDNF immunoreactivity in 15 patients with ES, 12 patients with PNES, and 17 healthy volunteers. Plasma [corrected] BDNF levels were measured using an enzyme-linked immunoassay.Healthy controls showed higher BDNF levels (4,289 ± 1,810 pg/mL) compared to patients with PNES (1,033 ± 435 pg/mL) (p0.001). However, unexpectedly, healthy controls also showed higher levels of BDNF compared to patients with ES without comorbid MDD (977 ± 565 pg/mL) (p0.001).Unlike children, adults with epilepsy appear to have decreased levels of plasma [corrected] BDNF. Reduced plasma [corrected] BDNF levels can be used to differentiate adult patients with ES or PNES from healthy controls. Further human studies are needed to better understand the pathophysiology explaining the decreased plasma [corrected] BDNF levels found in epilepsy and in PNES.

Objective: There have been few treatment trials for psychogenic nonepileptic seizures (PNES). Some psychotherapies have been shown to improve PNES and comorbid symptom outcomes. We evaluated a pharmacologic intervention to test the hypothesis that sertraline would reduce PNES. Methods: We conducted a pilot, double-blind, randomized, placebo-controlled trial in an academic medical hospital with epilepsy center outpatients. Subjects aged 18 to 65 years diagnosed with video-EEG–confirmed PNES were treated with flexible-dose sertraline or placebo over 12 weeks. Seizure calendars and symptom scales were charted prospectively. Secondary outcome measures included psychiatric symptom scales and psychosocial variables. Results: Thirty-eight subjects enrolled, and 26 (68%) completed the trial. Thirty-three subjects with nonzero nonepileptic seizure rates at baseline were included in intent-to-treat analysis of the primary outcome. Subjects assigned to the sertraline arm experienced a 45% reduction in seizure rates from baseline to final visit ( p = 0.03) vs an 8% increase in placebo ( p = 0.78). Secondary outcome scales revealed no significant between-group differences in change scores from baseline to final visit, after adjustment for differences at baseline. Conclusions: PNES were reduced in patients treated with a serotonin selective reuptake inhibitor, whereas those treated with placebo slightly increased. This study provides feasibility data for a larger-scale study. Level of evidence: This study provides Class II evidence that flexible-dose sertraline up to a maximum dose of 200 mg is associated with a nonsignificant reduction in PNES rate compared with a placebo control arm (risk ratio 0.51, 95% confidence interval 0.25–1.05, p = 0.29), adjusting for differences at baseline.

Comonitoring of seizures and respiratory function with pulse oximetry has shown that ictal respiratory changes (IRCs) accompany tonic-clonic convulsions and even partial seizures, especially those of temporal lobe origin. IRCs occur in children and adults, and diminished central drive is frequent, although peripheral obstruction is observed occasionally. Case reports of sudden unexplained death in epilepsy (SUDEP) have suggested IRC as a mechanism. In a series of 15 witnessed SUDEP cases, overt convulsions with marked respiratory difficulty were observed in 12. For two cases, obstructive mechanisms may have predominated. One near-SUDEP case implicated central apnea, but another case implicated postictal laryngospasm. Inhibition of brainstem respiratory control circuits likely subserves IRCs. The pre-Bötzinger complex in the rostral ventrolateral medulla is a key locus for respiratory rhythm generation, with expiratory control neurons near the nucleus ambiguous. Inputs to these neurons descend from the insula, hypothalamus, and reticular formation. Direct stimulation of limbic targets in humans causes apnea. Animal models of focal seizures with IRCs and SUDEP have produced inconsistent results: some support central mechanisms, whereas others implicate peripheral obstruction. Serotonin seems relevant in a mouse model of SUDEP. These models may elucidate how seizures embarrass respiration and possibly predispose patients to SUDEP.

The incidence of epilepsy is higher in the elderly than in younger adults. This community presents a challenging set of considerations in diagnosis and management. Numerous other processes may mimic seizures in the elderly. After careful diagnosis, AED choices should take into account metabolism, drug-drug in interactions, co-morbidities, and side effect profiles while striving to achieve seizure freedom.

Background Musical hallucinations (MHs) are rare and most often described in patients with hearing loss, female sex, older age, and various brain pathologies, including epilepsy. Case history We describe a unique case in which, after successful left temporal lobectomy for refractory epilepsy and subsequent ototoxic therapies, a 49-year-old man experienced the onset of songs replaying constantly in his mind for days to weeks. He had intractable partial epilepsy since age 26. Presurgical neurodiagnostic evaluations revealed a left temporal focus, left hippocampal magnetic resonance imaging abnormalities, bilateral language representation, and cognitive deficits lateralized to the left hemisphere. He underwent a partial left temporal lobectomy but required repeated antibiotic courses for postoperation bone flap infections, resulting in tinnitus. Surgery led to near seizure-freedom, plus improved cognitive and emotional function. Pathology revealed focal cortical dysplasia. Six months postsurgery, during antibiotic treatment, he began to hear songs replaying in his head, which increased in frequency over ensuing years. Conclusions We report, to our knowledge, the first case of MHs associated with temporal lobectomy for epilepsy. This patient had multiple risk factors for these unwanted musical experiences, including epilepsy, mild neuropsychiatric dysfunction, and tinnitus plus hearing loss. Possible mechanisms for MHs are discussed.

This chapter addresses the related topics of focal and generalized slowing, coma, and brain death. These EEG abnormalities are encountered in a wide range of clinical situations of variable severity. Focal and generalized slowing are both common and highly nonspecific findings in the EEG laboratory. Despite their lack of etiological specificity, EEG slowing and related patterns often bear important implications for both the location of CNS abnormalities and/or the prognosis for neurological recovery.

Somatosensory evoked potentials (SSEPs) are electrical potentials generated by various portions of the ascending sensory pathways in response to stimulation of peripheral sensory nerves. SSEPs can be easily elicited and recorded and can be used to examine the functional integrity of somatosensory pathways. This chapter summarizes the methodology for the recording of SSEPs, as well as their role in the evaluation of processes that may affect ascending sensory pathways (e.g., demyelination), and highlights their particular usefulness as an intraoperative tool during spinal cord surgery.

The object of this chapter is to familiarize the reader with a number of commonly encountered normal variants of brain-derived EEG activity. The term “normal variant pattern” refers to those rhythms or waveforms that have features reminiscent of either interictal or ictal EEG abnormalities. However, these patterns have been found in a substantial proportion of tracings from healthy subjects and, therefore, are not currently thought to represent pathological entities. It is, therefore, vital that such patterns be appropriately recognized by the EEG reader as normal variants and not erroneously confused for pathological patterns. This chapter addresses four main categories of variant EEG activity: 1. Rhythmic patterns. 2. Epileptiform patterns. 3. Lambda and lambdoids. 4. Age-related variants.