Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity.

Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.

Anticipation-induced delta phase reset improves human olfactory perception.

Anticipating an odor improves detection and perception, yet the underlying neural mechanisms of olfactory anticipation are not well understood. In this study, we used human intracranial electroencephalography (iEEG) to show that anticipation resets the phase of delta oscillations in piriform cortex prior to odor arrival. Anticipatory phase reset correlates with ensuing odor-evoked theta power and improvements in perceptual accuracy. These effects were consistently present in each individual subject and were not driven by potential confounds of pre-inhale motor preparation or power changes. Together, these findings suggest that states of anticipation enhance olfactory perception through phase resetting of delta oscillations in piriform cortex.

Early Seizures Are Predictive of Worse Health-Related Quality of Life at Follow-Up After Intracerebral Hemorrhage.

OBJECTIVES: Early seizures are a common complication of intracerebral hemorrhage, occurring in ~10% of patients. However, the independent effect of early seizures on patient outcomes, particularly health-related quality of life, is unclear. Without a potential benefit to patient outcomes, the widespread use (~40%) of prophylactic seizure medications has no reasonable chance of improving patient outcomes. We tested the hypothesis that health-related quality of life at follow-up is different between patients with and without early seizures (and secondarily, with nonconvulsive status epilepticus) after intracerebral hemorrhage. DESIGN: Patients with intracerebral hemorrhage were enrolled in an observational cohort study that prospectively collected clinical data and health-related quality of life at follow-up. SETTING: Academic medical center. PATIENTS: One-hundred thirty-three patients whose health-related quality of life was assessed 3 months after intracerebral hemorrhage onset. MEASUREMENTS AND MAIN RESULTS: Health-related quality of life was obtained at 3 months after intracerebral hemorrhage onset. T Scores of health-related quality of life were modeled with multivariable linear models accounting for severity with the intracerebral hemorrhage Score and hematoma location. Health-related quality of life was measured with National Institutes of Health Patient Reported Outcomes Measurement Information System/Neuroquality of life, expressed in T Scores (U.S. normal 50 ± 10). The modified Rankin Scale (a global measure) was a secondary outcome. There were 12 patients (9%) with early seizures. T Scores of health-related quality of life at follow-up were lower (worse) in patients with early seizure compared with patients without an early seizure (44 [32.75-51.85] vs 30.25 [18.9-39.15]; p = 0.04); results for other domains of health-related quality of life were similar. The association persisted in multivariable models. There was no association between early seizures and prophylactic seizure medications (p = 0.4). Results for patients with nonconvulsive status epilepticus were similar. There was no association between early seizures and the modified Rankin Scale at 3 months. CONCLUSIONS: Early seizures and nonconvulsive status epilepticus were associated with lower health-related quality of life at follow-up in survivors of intracerebral hemorrhage.

Efficacy of clobazam as add-on therapy in brain tumor-related epilepsy.

PURPOSE: Brain tumor-related epilepsy (TRE) is often resistant to currently available antiepileptic medications (AEDs). Clobazam was initially approved as adjunctive AED for patients with Lennox Gastaut syndrome but has been used in TRE, despite limited evidence in this context. This observational study aims to examine the effect of clobazam on seizure frequency on patients who have a primary CNS tumor and continued seizures despite their current AEDs. METHODS: A retrospective review of patients with histologically-confirmed primary brain tumors seen in the neuro-oncology interdisciplinary clinic from April 2016-2019 was completed, and patients on clobazam were identified. Response to clobazam was defined as a greater than 50% reduction in seizure frequency. Additional data including patient and tumor characteristics, treatment course, tolerability, AEDs used prior to addition of clobazam, and AEDs concomitantly used with clobazam were collected. RESULTS: A total of 35 patients with TRE on clobazam were identified, with 2 patients unable to tolerate the medication due to side effects. Of the 33 remaining patients, a total of 31 (93.9%) of patients were deemed responders. Ten patients (30.3%) were seizure free within 6 months of clobazam initiation and 21 (63.6%) reported a significant reduction in seizure frequency. This reduction also allowed several patients to modify concurrent AEDs. CONCLUSIONS: Clobazam is an effective agent to use as add-on AED in TRE, with 94% of patients showing a significant response within 6 months. Furthermore, the addition of clobazam may yield a reduction in polypharmacy, as concomitant AEDs can be reduced and potentially withdrawn.

Seizure outcome in patients with cavernous malformation after early surgery.

OBJECTIVE: To describe seizure outcome and complications in patients with cavernous malformations (CM) undergoing early versus late surgery. METHODS: A database was created for all CM patients who presented with seizure referred to the neurosurgical clinic at an academic center. A telephone survey and chart review were conducted to evaluate for preoperative and postoperative seizure frequency. Postoperative seizure-free outcome of patients who had ≤2 preoperative seizures versus those that had >2 preoperative seizures was compared. RESULTS: A total of 35 CM patients were included for analysis. Nineteen patients had ≤2 preoperative seizures and 16 patients had >2 preoperative seizures, six of them drug resistant for over two years. Among the ≤2 seizure group, 15 had only a single seizure before surgical resection. 94.7% of patients with ≤2 preoperative seizures and 62.5% of patients with >2 preoperative seizures were seizure free one year following surgical resection (p = 0.019). 78.9% of patients with ≤2 preoperative seizures and 25% of patients with >2 preoperative seizures were able to wean off AEDs (p < 0.001). Among those patients who had a single preoperative seizure, 100% of patients were seizure free at one year. CONCLUSIONS: Early surgical resection for CM patients who present after a CM-related seizure is an effective, well tolerated treatment and has good chance to offer seizure freedom without the need for long-term antiepileptic medications. Outcome for patients operated with only one or two preoperative seizures may lead to better results than patients who delay the procedure.

Counseling by epileptologists affects contraceptive choices of women with epilepsy.

INTRODUCTION: There are several important interactions between antiepileptic drugs (AEDs) and hormonal contraception that need to be carefully considered by women with epilepsy (WWE) and their practitioners. Many AEDs induce hepatic enzymes and decrease the efficacy of hormonal contraception. In addition, estrogen-containing hormonal contraception can increase the metabolism of lamotrigine, the most commonly prescribed AED in women of childbearing age. The intrauterine device (IUD) is a highly effective form of reversible contraception without AED drug interactions that is considered by many to be the contraceptive of choice for WWE. Women with epilepsy not planning pregnancy require effective contraceptive counseling that should include discussion of an IUD. There are no guidelines, however, on who should deliver these recommendations. The objective of this study was to explore the hypothesis that contraceptive counseling by a neurologist can influence the contraceptive choices of WWE. In particular, we explored the relationship between contraceptive counseling in the epilepsy clinic and the likelihood that patients would obtain an IUD. METHODS: We conducted a retrospective chart review of female patients age 18-45 seen at our institution for an initial visit between 2010 and 2014 to ascertain the type of contraceptive counseling each patient received as well as AED use and contraceptive methods. Patients who were pregnant or planning pregnancy at the first visit were excluded from further analyses as were patients with surgical sterilization. We also examined a subgroup of 95 patients with at least 4 follow-up visits to evaluate the efficacy of epileptologists' counseling. Specifically, we looked at the likelihood a patient obtained an IUD based on the type of counseling she had received. Fisher exact tests assessed associations between counseling type and whether patients had obtained an IUD. RESULTS: Three hundred and ninety-seven women met criteria for inclusion. Only 35% of female patients were counseled about contraception at the first visit. If women were not counseled at the first visit, they were unlikely to be counseled at subsequent visits; only 37% had ever received counseling by their fourth visit. Of the 95 patients who completed 4 visits, 28.4% were counseled about an IUD as an optimal contraceptive choice, 38.9% were generally counseled about contraceptive interactions, and 32.6% were not counseled about contraception. Women with epilepsy who received IUD-specific counseling were significantly more likely to switch to an IUD (44.4%) compared with women who received no contraceptive counseling (6.5%; p=0.0009). Women with epilepsy who received IUD-specific counseling also tended to switch to an IUD more often than those women receiving general counseling about AEDs and contraceptive interactions (18.9%; p=0.027). There was no significant difference in the likelihood of acquiring an IUD between the general counseling and no counseling groups. CONCLUSIONS: Contraceptive counseling by epileptologists and specific mention of an IUD is significantly associated with patient selection of an IUD as a contraceptive method. This suggests that neurologists can play an important role in patients' contraceptive choices.

New-Onset Seizure in Adults and Adolescents: A Review.

Importance: Approximately 8% to 10% of the population will experience a seizure during their lifetime. Only about 2% to 3% of patients go on to develop epilepsy. Understanding the underlying etiology leading to an accurate diagnosis is necessary to ensure appropriate treatment and that patients with low risk for recurrence are not treated unnecessarily. Observations: Patients can present with new-onset seizure for a variety of reasons such as acute symptomatic seizures due to acute brain injury or metabolic derangements, or unprovoked seizures that are the initial manifestation of epilepsy. A patient history and physical examination may identify features more consistent with an epileptic event and laboratory studies and brain imaging can identify an acute insult contributing to the presentation. Patients diagnosed with first-time unprovoked seizure require electroencephalography and epilepsy protocol-specific magnetic resonance imaging of the brain, which includes thin-cut coronal slices to determine risk of recurrence and the need for long-term treatment. In patients who meet the criteria for diagnosis of epilepsy, a carefully selected antiepileptic medication with consideration of comorbidities, adverse effect profile, and type of epilepsy is essential along with appropriate counseling. Conclusions and Relevance: Approximately 3% of the population will develop epilepsy but 2 to 3 times as many patients will experience a single seizure or seizure-like event. A diagnosis of epilepsy has significant medical, social, and emotional consequences. A careful patient history and physical examination, electroencephalography, and brain imaging are necessary to separate patients with acute symptomatic seizures, single unprovoked seizures, and nonepileptic events from those with new-onset epilepsy.

Extracting kinetic information from human motor cortical signals.

Brain machine interfaces (BMIs) have the potential to provide intuitive control of neuroprostheses to restore grasp to patients with paralyzed or amputated upper limbs. For these neuroprostheses to function, the ability to accurately control grasp force is critical. Grasp force can be decoded from neuronal spikes in monkeys, and hand kinematics can be decoded using electrocorticogram (ECoG) signals recorded from the surface of the human motor cortex. We hypothesized that kinetic information about grasping could also be extracted from ECoG, and sought to decode continuously-graded grasp force. In this study, we decoded isometric pinch force with high accuracy from ECoG in 10 human subjects. The predicted signals explained from 22% to 88% (60 ± 6%, mean ± SE) of the variance in the actual force generated. We also decoded muscle activity in the finger flexors, with similar accuracy to force decoding. We found that high gamma band and time domain features of the ECoG signal were most informative about kinetics, similar to our previous findings with intracortical LFPs. In addition, we found that peak cortical representations of force applied by the index and little fingers were separated by only about 4mm. Thus, ECoG can be used to decode not only kinematics, but also kinetics of movement. This is an important step toward restoring intuitively-controlled grasp to impaired patients.

"Ictal" lateralized periodic discharges.

OBJECTIVE: Whether lateralized periodic discharges (LPDs) represent ictal or interictal phenomena, and even the circumstances in which they may represent one or the other, remains highly controversial. Lateralized periodic discharges are, however, widely accepted as being ictal when they are time-locked to clinically apparent symptoms. We sought to investigate the characteristics of "ictal" lateralized periodic discharges (ILPDs) defined by time-locked clinical symptoms in order to explore the utility of using this definition to dichotomize LPDs into "ictal" and "nonictal" categories. METHODS: Our archive of all continuous EEG (cEEG) reports of adult inpatients undergoing prolonged EEG monitoring for nonelective indications between 2007 and 2011 was searched to identify all reports describing LPDs. Lateralized periodic discharges were considered ILPDs when they were reported as being consistently time-locked to clinical symptoms; LPDs lacking a clear time-locked correlate were considered to be "nonictal" lateralized periodic discharges (NILPDs). Patient charts and available neuroimaging studies were also reviewed. Neurophysiologic localization of LPDs, imaging findings, presence of seizures, discharge outcomes, and other demographic factors were compared between patients with ILPDs and those with NILPDs. p-Values were adjusted for false discovery rate (FDR). RESULTS: One thousand four hundred fifty-two patients underwent cEEG monitoring at our institution between 2007 and 2011. Lateralized periodic discharges were reported in 90 patients, 10 of whom met criteria for ILPDs. Nine of the patients with ILPDs demonstrated motor symptoms, and the remaining patient experienced stereotyped sensory symptoms. Ictal lateralized periodic discharges had significantly increased odds for involving central head regions (odds ratio [OR]=11; 95% confidence interval [CI]=2.16-62.6; p=0.018, FDR adjusted), with a trend towards higher proportion of lesions involving the primary sensorimotor cortex (p=0.09, FDR adjusted). CONCLUSIONS: When defined by the presence of a time-locked clinical correlate, ILPDs appear to be strongly associated with a central EEG localization. This is likely due to cortical irritability in central head regions having greater propensity to manifest with positive, clinically apparent, and time-locked symptoms. Thus, dichotomization of ILPDs and NILPDs on this basis principally reflects differences in underlying anatomical locations of the periodic discharges rather than providing a clinically salient categorization.

Incidence and Types of Cardiac Arrhythmias in the Peri-Ictal Period in Patients Having a Generalized Convulsive Seizure.

BACKGROUND AND OBJECTIVES: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases. METHODS: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during inpatient video-EEG monitoring for epilepsy evaluation. Exclusion criteria were status epilepticus and an obscured video recording. We analyzed semiologic and cardiorespiratory features through video-EEG (VEEG), electrocardiogram, thoracoabdominal bands, and pulse oximetry. We investigated the presence of bradycardia, asystole, supraventricular tachyarrhythmias (SVTs), premature atrial beats, premature ventricular beats, nonsustained ventricular tachycardia (NSVT), atrial fibrillation (Afib), ventricular fibrillation (VF), atrioventricular block (AVB), exaggerated sinus arrhythmia (ESA), and exaggerated sinus arrhythmia with bradycardia (ESAWB). A board-certified cardiac electrophysiologist diagnosed and classified the arrhythmia types. Bradycardia, asystole, SVT, NSVT, Afib, VF, AVB, and ESAWB were classified as arrhythmias of interest because these were of SUDEP pathophysiology value. The main outcome was the occurrence of seizure-induced arrhythmias of interest during inpatient VEEG monitoring. Moreover, yearly follow-up was conducted to identify SUDEP cases. Binary logistic generalized estimating equations were used to determine clinical-demographic and peri-ictal variables that were predictive of the presence of seizure-induced arrhythmias of interest. The z-score test for 2 population proportions was used to test whether the proportion of seizures and patients with postconvulsive ESAWB or bradycardia differed between SUDEP cases and survivors. RESULTS: This study includes data from 249 patients (mean age 37.2 ± 23.5 years, 55% female) who had 455 seizures. The most common arrhythmia was ESA, with an incidence of 137 of 382 seizures (35.9%) (106/224 patients [47.3%]). There were 50 of 352 seizure-induced arrhythmias of interest (14.2%) in 41 of 204 patients (20.1%). ESAWB was the commonest in 22 of 394 seizures (5.6%) (18/225 patients [8%]), followed by SVT in 18 of 397 seizures (4.5%) (17/228 patients [7.5%]). During follow-up (48.36 ± 31.34 months), 8 SUDEPs occurred. Seizure-induced bradycardia (3.8% vs 12.5%, z = -16.66, p < 0.01) and ESAWB (6.6% vs 25%; z = -3.03, p < 0.01) were over-represented in patients who later died of SUDEP. There was no association between arrhythmias of interest and seizure severity biomarkers (p > 0.05). DISCUSSION: Markers of seizure severity are not related to seizure-induced arrhythmias of interest, suggesting that other factors such as occult cardiac abnormalities may be relevant for their occurrence. Seizure-induced ESAWB and bradycardia were more frequent in SUDEP cases, although this observation was based on a very limited number of SUDEP patients. Further case-control studies are needed to evaluate the yield of arrhythmias of interest along with respiratory changes as potential SUDEP biomarkers.

Long-term monitoring of brain tumors: when is it necessary?

Tumors, particularly low grade glioma and glioneuronal tumors, account for 25-35% of patients who are undergoing epilepsy surgery for intractable seizures. A comprehensive epilepsy evaluation including video-electroencephalography (EEG) monitoring is useful for most of these patients, to determine the optimal extent of resection for the achievement of seizure-free outcome without causing postoperative deficits. Video-EEG monitoring for patients with brain tumor should also be considered in specific situations, such as patients with new postoperative seizures or advanced tumors with unexplained mental status change.

Assessment of a quasi-piezoelectric mattress monitor as a detection system for generalized convulsions.

The risk of sudden unexpected death in epilepsy (SUDEP) is highest with nocturnal, unattended generalized convulsions, and basic resuscitation may be able to prevent SUDEP. This study investigates an under-mattress device (ElectroMechanical Film - Emfit®) which is triggered by rhythmic motor activity of a specifiable duration, frequency, and intensity using a quasi-piezoelectric material sensitive to changes in mattress pressure. The device was tested during inpatient video-EEG monitoring. Eighteen GTCSs were recorded, 10 out of wakefulness and 8 out of sleep. Sixteen of the 18 seizures (89%) resulted in Emfit® activation with both false negative alarms occurring during wakefulness. On average, the device was activated within 9 s of onset of bilateral clonic motor movements (range: -37 to +39 s) and occurred, on average, 45 s before seizure end (range: 19 to 76 s). Only 21 false alarms were encountered, all occurring during wakefulness (PPV: 43%). The data suggest that the Emfit® detection device has a high predictive value for generalized convulsions, offers caregivers a reliable and early warning to assist the patient during convulsions, and may be a novel way to prevent SUDEP.

Auditory hallucinations as ictal phenomena in a patient with voltage-gated potassium channel antibody-associated limbic encephalitis.

Limbic encephalitis involving anti-voltage-gated potassium channel antibodies (VGKC-LE) has become increasingly recognised, with seizures and psychotic features, such as hallucinations being typical clinical manifestations. Though the literature supports auditory hallucinations as ictal phenomena, there are no reported cases of these hallucinations correlating with electrographic seizure for this disease entity. Early recognition of auditory hallucinations as seizures could alter treatment and subsequently affect short-term outcomes in these patients. We report the case of a patient with auditory hallucinations and progressive cognitive decline, as well as serological evidence of VGKC antibodies, in whom ictal hallucinations were identified by continuous video-EEG monitoring. This case highlights the subtlety of this entity, in both clinical and electrographic detection. [Published with video sequences].

High-Frequency Oscillations in Tumor-Related Epilepsy.

INTRODUCTION: To define the patient characteristics, tumor characteristics, and clinical course of patients with primary brain tumors with high-frequency oscillations (HFOs) recorded on electrocorticography. Furthermore, we evaluated whether the presence of HFOs portends a greater risk of postoperative tumor-related epilepsy and whether the resection of HFO-generating tissue reduces likelihood of postoperative tumor-related epilepsy. METHODS: This was a retrospective study of 35 patients undergoing awake craniotomy for tumor resection, all of whom underwent intraoperative electrocorticography. Electrocorticography data were reviewed to assess the presence of HFOs and determine their contact locations. The data were analyzed to determine whether HFO-generating tissue was included in the resection and relationship to postoperative seizure outcome. RESULTS: Seventeen patients (48.5%) were found to have HFOs. Very few patients (4 of 35, 11.4%) had sharp waves. Patients with and without HFOs did not significantly differ in demographics, presentation, tumor characteristics, or tumor molecular genetics. A history of seizures prior to resection was not associated with the presence of HFOs ( P = 0.62), although when patients had seizures during the same hospitalization as the resection, HFOs were more likely to be present ( P = 0.045). Extent of HFO resection was not associated with the likelihood of postoperative seizure freedom. CONCLUSIONS: Approximately half (48.5%) of patients undergoing resection for a primary brain tumor had HFOs. Although HFO resection was not shown to lead to improved seizure freedom, this study was limited by a small sample size, and further investigation into HFO resection and patient outcomes in this population is warranted.

Psychogenic gelastic seizures in a patient with hypothalamic hamartoma.

Gelastic seizures are classically associated with hypothalamic hamartoma. The most effective treatment for gelastic epilepsy is surgery, although confirming that a hypothalamic hamartoma is an epileptic lesion prior to surgical intervention is challenging. Here, we report the case of a patient with a hypothalamic hamartoma who was diagnosed with psychogenic non-epileptic gelastic seizures using video-EEG monitoring. [Published with video sequences].

Human hippocampal responses to network intracranial stimulation vary with theta phase.

Hippocampal-dependent memory is thought to be supported by distinct connectivity states, with strong input to the hippocampus benefitting encoding and weak input benefitting retrieval. Previous research in rodents suggests that the hippocampal theta oscillation orchestrates the transition between these states, with opposite phase angles predicting minimal versus maximal input. We investigated whether this phase dependence exists in humans using network-targeted intracranial stimulation. Intracranial local field potentials were recorded from individuals with epilepsy undergoing medically necessary stereotactic electroencephalographic recording. In each subject, biphasic bipolar direct electrical stimulation was delivered to lateral temporal sites with demonstrated connectivity to hippocampus. Lateral temporal stimulation evoked ipsilateral hippocampal potentials with distinct early and late components. Using evoked component amplitude to measure functional connectivity, we assessed whether the phase of hippocampal theta predicted relatively high versus low connectivity. We observed an increase in the continuous phase-amplitude relationship selective to the early and late components of the response evoked by lateral temporal stimulation. The maximal difference in these evoked component amplitudes occurred across 180 degrees of separation in the hippocampal theta rhythm; that is, the greatest difference in component amplitude was observed when stimulation was delivered at theta peak versus trough. The pattern of theta-phase dependence observed for hippocampus was not identified for control locations. These findings demonstrate that hippocampal receptivity to input varies with theta phase, suggesting that theta phase reflects connectivity states of human hippocampal networks. These findings confirm a putative mechanism by which neural oscillations modulate human hippocampal function.

United States Epilepsy Center Characteristics: A Data Analysis From the National Association of Epilepsy Centers.

BACKGROUND AND OBJECTIVES: Patients with drug-resistant epilepsy (DRE) may benefit from specialized testing and treatments to better control seizures and improve quality of life. Most evaluations and procedures for DRE in the United States are performed at epilepsy centers accredited by the National Association of Epilepsy Centers (NAEC). On an annual basis, the NAEC collects data from accredited epilepsy centers on hospital-based epilepsy monitoring unit (EMU) size and admissions, diagnostic testing, surgeries, and other services. This article highlights trends in epilepsy center services from 2012 through 2019. METHODS: We analyzed data reported in 2012, 2016, and 2019 from all level 3 and level 4 NAEC accredited epilepsy centers. Data were described using frequency for categorical variables and median for continuous variables and were analyzed by center level and center population category. EMU beds, EMU admissions, epileptologists, and aggregate procedure volumes were also described using rates per population per year. RESULTS: During the period studied, the number of NAEC accredited centers increased from 161 to 256, with the largest increases in adult- and pediatric-only centers. Growth in EMU admissions (41%), EMU beds (26%), and epileptologists (109%) per population occurred. Access to specialized testing and services broadly expanded. The largest growth in procedure volumes occurred in laser interstitial thermal therapy (LiTT) (61%), responsive neurostimulation (RNS) implantations (114%), and intracranial monitoring without resection (152%) over the study period. Corpus callosotomies and vagus nerve stimulator (VNS) implantations decreased (-12.8% and -2.4%, respectively), while growth in temporal lobectomies (5.9%), extratemporal resections (11.9%), and hemispherectomies/otomies (13.1%) lagged center growth (59%), leading to a decrease in median volumes of these procedures per center. DISCUSSION: During the study period, the availability of specialty epilepsy care in the United States improved as the NAEC implemented its accreditation program. Surgical case complexity increased while aggregate surgical volume remained stable or declined across most procedure types, with a corresponding decline in cases per center. This article describes recent data trends and current state of resources and practice across NAEC member centers and identifies several future directions for driving systematic improvements in epilepsy care.

Impact of the COVID-19 Pandemic on Epilepsy Center Practice in the United States.

BACKGROUND AND OBJECTIVES: Persons with epilepsy, especially those with drug resistant epilepsy (DRE), may benefit from inpatient services such as admission to the epilepsy monitoring unit (EMU) and epilepsy surgery. The COVID-19 pandemic caused reductions in these services within the US during 2020. This article highlights changes in resources, admissions, and procedures among epilepsy centers accredited by the National Association of Epilepsy Centers (NAEC). METHODS: We compared data reported in 2019, prior to the COVID-19 pandemic, and 2020 from all 260 level 3 and level 4 NAEC accredited epilepsy centers. Data were described using frequency for categorical variables and median for continuous variables and were analyzed by center level, center population category, and geographical location. Qualitative responses from center directors to questions regarding the impact from COVID-19 were summarized utilizing thematic analysis. Responses from the NAEC center annual reports as well as a supplemental COVID-19 survey were included. RESULTS: EMU admissions declined 23% (-21,515) in 2020, with largest median reductions in level 3 centers [-55 admissions (-44%)] and adult centers [-57 admissions (-39%)]. The drop in admissions was more substantial in the East North Central, East South Central, Mid Atlantic, and New England US Census divisions. Survey respondents attributed reduced admissions to re-assigning EMU beds, restrictions on elective admissions, reduced staffing, and patient reluctance for elective admission. Treatment surgeries declined by 371 cases (5.7%), with the largest reduction occurring in VNS implantations [-486 cases (-19%)] and temporal lobectomies [-227 cases (-16%)]. All other procedure volumes increased, including a 35% (54 cases) increase in corpus callosotomies. DISCUSSION: In the US, access to care for persons with epilepsy declined during the COVID-19 pandemic in 2020. Adult patients, those relying on level 3 centers for care, and many persons in the eastern half of the US were most affected.

Development and Validation of the 5-SENSE Score to Predict Focality of the Seizure-Onset Zone as Assessed by Stereoelectroencephalography.

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified. Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated. Design, Setting, and Participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021. Main Outcomes and Measures: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample. Results: A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age, 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity. Conclusions and Relevance: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

Aphasic status epilepticus: electroclinical correlation.

PURPOSE: Aphasic status epilepticus (ASE) in otherwise awake patients is a rare phenomenon. We present a series of nine consecutive patients with ASE to characterize clinical, electrophysiologic, and imaging findings. METHODS: Nine patients in ASE were identified between July 2006 and December 2009 at our institution. Each was evaluated by the neurology service and monitored with video-electroencephalography (EEG) for at least 24 h. Thorough, repeated language testing was correlated with EEG findings. KEY FINDINGS: All nine patients were right-handed with subacute or chronic left hemispheric lesions on magnetic resonance imaging (MRI). All patients had mixed aphasia, three presenting with persistent aphasia from onset and six with episodic speech impairment, which became persistent in five of the six. The initial 30-min EEG demonstrated electrographic seizure in only five patients (56%), despite the presence of aphasia during the recording. Left hemispheric periodic lateralized epileptiform discharges (PLEDS) were seen in two patients, and left hemispheric slowing in two patients. Continuous video-EEG monitoring confirmed electrographic seizure activity in all nine patients. Peak electrographic seizure frequency varied from continuous to once every 2 h and was not associated with fluctuations in the speech deficit. EEG seizures resolved abruptly in three patients and gradually over up to 4 days in six patients. Clinical improvement was delayed in eight of the nine patients, and four patients retained some aphasia at discharge, 2-4 days after EEG seizure resolution. SIGNIFICANCE: Standard EEG is sensitive for detection of abnormalities in the dominant hemisphere in patients with ASE. However, continuous EEG is necessary to confirm the diagnosis and monitor treatment, since clinical symptoms do not correlate with electrographic seizure activity and do not provide sufficient information to guide treatment decisions.