Epilepsy phenotype and its reproducibility after lateral fluid percussion-induced traumatic brain injury in rats: Multicenter EpiBioS4Rx study project 1.

OBJECTIVE: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites. METHODS: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis. RESULTS: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites). SIGNIFICANCE: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.

Efficacy of verbal suggestion, verbal suggestion with a tuning fork, and verbal suggestion with a cotton swab for inducing the paroxysmal event during video-EEG recording in children with suspected psychogenic nonepileptic seizures.

INTRODUCTION: Video-electroencephalogram (EEG) with suggestion is widely considered the gold standard for diagnosing psychogenic nonepileptic seizures (PNES). However, ethical concerns and uncertainties persist regarding the most minimally invasive and least deceptive suggestion approach. MATERIALS AND METHODS: In an open-label randomized controlled trial, we evaluated the effectiveness of three suggestion methods (verbal suggestion, verbal suggestion with a tuning fork, and verbal suggestion with a cotton swab) during short-term video-EEG (STVEEG) recordings to induce PNES in children aged 5-18 years. If the paroxysmal event couldn't be elicited with the assigned method, alternative techniques were employed. RESULTS: Out of 97 initially screened children, 75 were enrolled, with 25 in each group. The efficacy of all three suggestion methods was comparable in reproducing paroxysmal events (success rate of 16/25, 17/25 and 17/25 in verbal suggestion only, verbal suggestion with tuning fork and sterile cotton swab group respectively, p = 0.83) and the time required for induction (median of 2, 3 and 3 min respectively, p = 0.21). After trying alternative methods, 20 %, 12 %, and 12 % more patients in these three groups, respectively, were able to reproduce the paroxysmal event, with the differences not reaching statistical significance (p = 0.74). The assigned induction method or the success/failure of event reproduction did not significantly impact clinical outcomes at 12 weeks, and none of the patients in whom PNES could not be reproduced during STVEEG were later found to have an organic cause. Only the presence of psychiatric comorbidity independently predicted successful event reproduction during STVEEG, with statistical significance even after adjusting for other variables (p = 0.03). CONCLUSION: The efficacy of verbal suggestion alone in inducing paroxysmal nonepileptic seizures is on par with using a tuning fork or cotton swab in conjunction with verbal suggestion during STVEEG.

Diagnostic utility of prolonged ambulatory video-electroencephalography monitoring.

OBJECTIVES: Ambulatory video-electroencephalography (video-EEG) represents a low-cost, convenient and accessible alternative to inpatient video-EEG monitoring, however few studies have examined their diagnostic yield. In this large-scale retrospective study conducted in Australia, we evaluated the efficacy of prolonged ambulatory video-EEG recordings in capturing diagnostic events and resolving the referring question. METHODS: Sequential adult and paediatric ambulatory video-EEG reports from April 2020 to June 2021 were reviewed retrospectively. Data collection included patient demographics, clinical information, and details of events and EEG abnormalities. Clinical utility was assessed by examining i) time to first diagnostic event, and ii) ability to resolve the referring questions - seizure localisation, quantification, classification, and differentiation (differentiating seizures from non-epileptic events). RESULTS: Of the 600 reports analysed, 49 % captured at least one event, and 45 % captured interictal abnormalities (epileptiform or non-epileptiform). Seizures, probable psychogenic events (mostly non-convulsive), and other non-epileptic events occurred in 13 %, 23 % and 21 % of recordings respectively, with overlap. Unreported events were captured in 53 (9 %) recordings, and unreported seizures represented more than half of all seizures captured (51 %, 392/773). Nine percent of events were missing clinical, video or electrographic data. A diagnostic event occurred in 244 (41 %) recordings, of which 14 % were captured between the fifth and eighth day of recording. Reported event frequency ≥ 1/week was the only significant predictor of diagnostic event capture. In recordings with both seizures and psychogenic events, unrecognized seizures were frequent, and seizures may be missed if recording is terminated early. The referring question was resolved in 85 % of reports with at least one event, and 53 % of all reports. Specifically, this represented 46 % of reports (235/512) for differentiation of events, and 75 % of reports (27/36) for classification of seizures. CONCLUSION: Ambulatory video-EEG recordings are of high diagnostic value in capturing clinically relevant events and resolving the referring clinical questions.

Factors affecting long-term prognosis in adult patients with psychogenic non-epileptic seizures.

Background and purpose:

Among epileptic patients who are monitored using the video-electroencephalography monitoring (VEM) technique, in some patients a psychogenic non-epileptic seizure (PNES) can be identified as a definitive diagnosis. The long-term prognosis of these patients is not well known. In this study, we aimed to determine the factors that affect the prognosis of PNES.

Forty-one PNES patients diagnosed using VEM between 2012 and 2022 were questioned about their PNES frequencies in the last 12 months. According to their semiological characteristics, PNES types were divided into motor and non-motor seizures. The effects of clinical characteristics (e.g. age, gender, marital status, education level and PNES type) on the prognoses were identified. 

Twenty-one PNES patients (51.2%) had long-term seizure freedom after VEM. Thirteen of them (31.7%) entered the seizure-free period immediately after VEM, and the other eight (19.5%) continued suffering from PNES for several years and became seizure free in the last 12 months. In the poor-prognosis group, female cases showed worse prognoses than male cases. The prognoses of motor and non-motor PNES types did not show significant differences. 

This study showed that 51.2% of the PNES patients examined had long-term seizure freedom and that female patients had worse prognoses than male patients.

Epm2aR240X knock-in mice present earlier cognitive decline and more epileptic activity than Epm2a-/- mice.

Lafora disease is a rare recessive form of progressive myoclonic epilepsy, usually diagnosed during adolescence. Patients present with myoclonus, neurological deterioration, and generalized tonic-clonic, myoclonic, or absence seizures. Symptoms worsen until death, usually within the first ten years of clinical onset. The primary histopathological hallmark is the formation of aberrant polyglucosan aggregates called Lafora bodies in the brain and other tissues. Lafora disease is caused by mutations in either the EPM2A gene, encoding laforin, or the EPM2B gene, coding for malin. The most frequent EPM2A mutation is R241X, which is also the most prevalent in Spain. The Epm2a-/- and Epm2b-/- mouse models of Lafora disease show neuropathological and behavioral abnormalities similar to those seen in patients, although with a milder phenotype. To obtain a more accurate animal model, we generated the Epm2aR240X knock-in mouse line with the R240X mutation in the Epm2a gene, using genetic engineering based on CRISPR-Cas9 technology. Epm2aR240X mice exhibit most of the alterations reported in patients, including the presence of LBs, neurodegeneration, neuroinflammation, interictal spikes, neuronal hyperexcitability, and cognitive decline, despite the absence of motor impairments. The Epm2aR240X knock-in mouse displays some symptoms that are more severe that those observed in the Epm2a-/- knock-out, including earlier and more pronounced memory loss, increased levels of neuroinflammation, more interictal spikes and increased neuronal hyperexcitability, symptoms that more precisely resemble those observed in patients. This new mouse model can therefore be specifically used to evaluate how new therapies affects these features with greater precision.

Variable Association of Physiologic Changes With Electrographic Seizure-Like Events in Infants Born Preterm.

OBJECTIVES: To determine the incidence of seizure-like events in a cohort of infants born preterm as well as the prevalence of associated vital sign changes (heart rate [HR], respiratory rate, and pulse oximetry [SpO2]). STUDY DESIGN: We performed prospective conventional video electroencephalogram monitoring on infants born at 23-30 weeks of gestational age during the first 4 postnatal days. For detected seizure-like events, simultaneously captured vital sign data were analyzed during the pre-event baseline and during the event. Significant vital sign changes were defined as HR or respiratory rate >±2 SD from the infant's own baseline physiologic mean, derived from a 10-minute interval before the seizure-like event. Significant change in SpO2 was defined as oxygen desaturation during the event with a mean SpO2 <88%. RESULTS: Our sample included 48 infants with median gestational age of 28 weeks (IQR 26-29) and birth weight of 1125 g (IQR 963-1265). Twelve (25%) infants had seizure-like discharges with a total of 201 events; 83% (10/12) of infants had vital sign changes during these events, and 50% (6/12) had significant vital sign changes during the majority of the seizure-like events. Concurrent HR changes occurred the most frequently. CONCLUSIONS: Individual infant variability was observed in the prevalence of concurrent vital sign changes with electroencephalographic seizure-like events. Physiologic changes associated with preterm electrographic seizure-like events should be investigated further as a potential biomarker to assess the clinical significance of such events in the preterm population.

Clinical seizure semiology is subtle and identification of seizures by parents is unreliable in infants with tuberous sclerosis complex.

OBJECTIVE: The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording. METHODS: Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video-EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification. RESULTS: Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients. SIGNIFICANCE: This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions.

E2730, an uncompetitive γ-aminobutyric acid transporter-1 inhibitor, suppresses epileptic seizures in a rat model of chronic mesial temporal lobe epilepsy.

OBJECTIVE: More than one third of mesial temporal lobe epilepsy (MTLE) patients are resistant to current antiseizure medications (ASMs), and half experience mild-to-moderate adverse effects of ASMs. There is therefore a strong need to develop and test novel ASMs. The objective of this work is to evaluate the pharmacokinetics and neurological toxicity of E2730, a novel uncompetitive inhibitor of γ-aminobutyric acid transporter-1, and to test its seizure suppression effects in a rat model of chronic MTLE. METHODS: We first examined plasma levels and adverse neurological effects of E2730 in healthy Wistar rats. Adult male rats were implanted with osmotic pumps delivering either 10, 20, or 100 mg/kg/day of E2730 subcutaneously for 1 week. Blood sampling and behavioral assessments were performed at several timepoints. We next examined whether E2730 suppressed seizures in rats with chronic MTLE. These rats were exposed to kainic acid-induced status epilepticus, and 9 weeks later, when chronic epilepsy was established, were assigned to receive one of the three doses of E2730 or vehicle for 1 week in a randomized crossover design. Continuous video-electroencephalographic monitoring was acquired during the treatment period to evaluate epileptic seizures. RESULTS: Plasma levels following continuous infusion of E2730 showed a clear dose-related increase in concentration. The drug was well tolerated at all doses, and any sedation or neuromotor impairment was mild and transient, resolving within 48 h of treatment initiation. Remarkably, E2730 treatment in chronically epileptic rats led to seizure suppression in a dose-dependent manner, with 65% of rats becoming seizure-free at the highest dose tested. Mean seizure class did not differ between the treatment groups. SIGNIFICANCE: This study shows that continuous subcutaneous infusion of E2730 over 7 days results in a marked, dose-dependent suppression of spontaneous recurrent seizures, with minimal adverse neurological effects, in a rat model of chronic MTLE. E2730 shows strong promise as an effective new ASM to be translated into clinical trials.

[Outpatient long-term video EEG as new diagnostic approach in Germany: results of a feasibility study]. / Ambulantes Langzeit-Video-EEG als neuer diagnostischer Ansatz in Deutschland: Ergebnisse einer Machbarkeitsstudie.

In Germany, long-term video EEG as the gold standard for the diagnostics of epilepsy and other seizure disorders, is currently only available for inpatient monitoring in a limited number of specialized centers. These limited monitoring capacities and the large amount of associated time and work resources lead to a significant waiting time for this important diagnostic procedure nationwide. New portable sensor technology and automated data analysis methods are creating opportunities for gold standard long-term video EEG assessments in outpatient settings, which may help to resolve this barrier. Here, we report the results of a single-center feasibility study by implementing outpatient long-term video EEG (ALVEEG) as a diagnostic pathway in Germany. In the new diagnostic pathway, the use of innovative, portable video EEG monitoring systems along with artificial intelligence-assisted data analysis are intended to provide those patients affected by seizure disorders with a more rapid, efficient, and cross-sectoral access to gold standard diagnostics in the home environment. The diagnostics were well accepted by patients and clinicians and may represent a complementary option to inpatient monitoring to eliminate current bottlenecks in diagnostics and care.

Peri-ictal heart rate changes in patients with epilepsy.

Background: Heart rate (HR) changes associated with seizures are promising biomarkers in epilepsy. Aims: The aim of our study is to reveal possible HR changes in the peri-ictal period. Methods: Long-term video-EEG monitorization records of generalized and focal epilepsy patients were reviewed. HRs were calculated in the pre-ictal (2 min before the first seizure activity in EEG), ictal (the time from the first seizure activity on the EEG to the end of the seizure), and in the interictal period (at least 2 h before or 12 h after the seizure). Interictal, pre-ictal, and ictal HRs were compared with each other. In addition, it was investigated whether peri-ictal HR changes differ between generalized and focal seizure patients. Results: Focal motor seizures were observed in 21, and generalized tonic-clonic seizures were observed in 18 of 39 (22 female and 17 male) patients studied. HRs in the pre-ictal and ictal periods were significantly higher than in the interictal period. This significant increase in HR was validated separately in both focal and generalized seizure groups and was not different between the two groups. Conclusion: Our study supports previous studies showing the presence of increased peri-ictal HR and also provides new insights by comparing focal and generalized motor seizures. We think that our findings may contribute to the development of early warning signs in epilepsy patients.

The unforeseen future: Impacts of the COVID-19 pandemic on home video-EEG telemetry.

The coronavirus disease 2019 (COVID-19) pandemic had widespread impact on health care systems globally-particularly services arranged around elective admission and attendance such as epilepsy monitoring units and home video-EEG telemetry (HVET). Here, we review the ongoing impacts of the pandemic on HVET services among several different providers who used different initial models of HVET. We discuss the features of HVET that led to success in providing continued diagnostic services to patients with epilepsy and related disorders and through retrospective audit of our services demonstrate the high diagnostic yield of HVET. We reflect on this unforeseen future and its implications for other diagnostic techniques and approaches.

Minimum standards for inpatient long-term video-electroencephalographic monitoring: A clinical practice guideline of the International League Against Epilepsy and International Federation of Clinical Neurophysiology.

The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long-term video-electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement. We found limited high-level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events. For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long-term outcome effects of LTVEM and to establish its clinical utility.

Diagnostic yield and limitations of in-hospital documentation in patients with epilepsy.

OBJECTIVE: To determine the diagnostic yield of in-hospital video-electroencephalography (EEG) monitoring to document seizures in patients with epilepsy. METHODS: Retrospective analysis of electronic seizure documentation at the University Hospital Freiburg (UKF) and at King's College London (KCL). Statistical assessment of the role of the duration of monitoring, and subanalyses on presurgical patient groups and patients undergoing reduction of antiseizure medication. RESULTS: Of more than 4800 patients with epilepsy undergoing in-hospital recordings at the two institutions since 2005, seizures with documented for 43% (KCL) and 73% (UKF).. Duration of monitoring was highly significantly associated with seizure recordings (p < .0001), and presurgical patients as well as patients with drug reduction had a significantly higher diagnostic yield (p < .0001). Recordings with a duration of >5 days lead to additional new seizure documentation in only less than 10% of patients. SIGNIFICANCE: There is a need for the development of new ambulatory monitoring strategies to document seizures for diagnostic and monitoring purposes for a relevant subgroup of patients with epilepsy in whom in-hospital monitoring fails to document seizures.

Seizure outcome determinants in children after surgery for single unilateral lesions on magnetic resonance imaging: Role of preoperative ictal and interictal electroencephalography.

OBJECTIVE: To determine whether an ictal electroencephalographic (EEG) recording as part of presurgical evaluation of children with a demarcated single unilateral magnetic resonance imaging (MRI) lesion is indispensable for surgical decision-making, we investigated the relationship of interictal/ictal EEG and seizure semiology with seizure-free outcome. METHODS: Data were obtained retrospectively from consecutive patients (≤18 years old) undergoing epilepsy surgery with a single unilateral MRI lesion at our institution over a 6-year period. Video-telemetry EEG (VT-EEG) was classified as concordant or nonconcordant/noninformative in relation to the MRI lesion location. The odds of seizure-free outcome associated with nonconcordant versus concordant for semiology, interictal EEG, and ictal EEG were compared separately. Multivariate logistic regression was conducted to correct for confounding variables. RESULTS: After a median follow-up of 26 months (interquartile range = 17-37.5), 73 (69%) of 117 children enrolled were seizure-free. Histopathological diagnoses included low-grade epilepsy-associated tumors, n = 46 (39%); focal cortical dysplasia (FCD), n = 33 (28%); mesial temporal sclerosis (MTS), n = 23 (20%); polymicrogyria, n = 3 (3%); and nondiagnostic findings/gliosis, n = 12 (10%). The odds of seizure freedom were lower with a nonconcordant interictal EEG (odds ratio [OR] = .227, 95% confidence interval [CI] = .079-.646, p = .006) and nonconcordant ictal EEG (OR = .359, 95% CI = .15-.878, p = .035). In the multivariate logistic regression model, factors predicting lower odds for seizure-free outcome were developmental delay/intellectual disability and higher number of antiseizure medications tried, with a nonsignificant trend for "nonconcordant interictal EEG." In the combined subgroup of patients with FCD and tumors (n = 79), there was no significant relationship of VT-EEG factors and seizure outcomes, whereas in children with MTS and acquired lesions (n = 25), a nonconcordant EEG was associated with poorer seizure outcomes (p = .003). SIGNIFICANCE: An ictal EEG may not be mandatory for presurgical evaluation, particularly when a well-defined single unilateral MRI lesion has been identified and the interictal EEG is concordant.

Bilateral temporal lobe epilepsy: How many seizures are required in chronic ambulatory electrocorticography to estimate the laterality ratio?

OBJECTIVE: This study was undertaken to measure the duration of chronic electrocorticography (ECoG) needed to attain stable estimates of the seizure laterality ratio in patients with drug-resistant bilateral temporal lobe epilepsy (BTLE). METHODS: We studied 13 patients with drug-resistant BTLE who were implanted for at least 1 year with a responsive neurostimulation device (RNS System) that provides chronic ambulatory ECoG. Bootstrap analysis and nonlinear regression were applied to model the relationship between chronic ECoG duration and the probability of capturing at least one seizure. Laterality of electrographic seizures in chronic ECoG was compared with the seizure laterality ratio from Phase 1 scalp video-electroencephalographic (vEEG) monitoring. The Kaplan-Meier estimator was used to evaluate time to seizure laterality ratio convergence. RESULTS: Seizure laterality ratios from Phase 1 scalp vEEG monitoring correlated poorly with those from RNS chronic ECoG (r = .31, p = .30). Across the 13 patients, average electrographic seizure frequencies ranged from 1.4 seizures/month to 5.1 seizures/day. A 50% probability of recording at least one electrographic seizure required 9.1 days of chronic ECoG, and 90% probability required 44.3 days of chronic ECoG. A median recording duration of 150.9 days (5 months), corresponding to a median of 16 seizures, was needed before confidence intervals for the seizure laterality ratio reliably contained the long-term value. The median recording duration before the point estimate of the seizure laterality ratio converged to a stationary value was 236.8 days (7.9 months). SIGNIFICANCE: RNS chronic ECoG overcomes temporal sampling limitations intrinsic to inpatient Phase 1 vEEG evaluations. In patients with drug-resistant BTLE, approximately 8 months of chronic RNS ECoG are needed to precisely estimate the seizure laterality ratio, with 75% of people with BTLE achieving convergence after 1 year of RNS recording. For individuals who are candidates for unilateral resection based on seizure laterality, optimized recording duration may help avert morbidity associated with delay to definitive treatment.

Automated seizure detection with noninvasive wearable devices: A systematic review and meta-analysis.

OBJECTIVE: This study was undertaken to review the reported performance of noninvasive wearable devices in detecting epileptic seizures and psychogenic nonepileptic seizures (PNES). METHODS: We conducted a systematic review and meta-analysis of studies reported up to November 15, 2021. We included studies that used video-electroencephalographic (EEG) monitoring as the gold standard to determine the sensitivity and false alarm rate (FAR) of noninvasive wearables for automated seizure detection. RESULTS: Twenty-eight studies met the criteria for the systematic review, of which 23 were eligible for meta-analysis. These studies (1269 patients in total, median recording time = 52.9 h per patient) investigated devices for tonic-clonic seizures using wrist-worn and/or ankle-worn devices to measure three-dimensional accelerometry (15 studies), and/or wearable surface devices to measure electromyography (eight studies). The mean sensitivity for detecting tonic-clonic seizures was .91 (95% confidence interval [CI] = .85-.96, I2  = 83.8%); sensitivity was similar between the wrist-worn (.93) and surface devices (.90). The overall FAR was 2.1/24 h (95% CI = 1.7-2.6, I2  = 99.7%); FAR was higher in wrist-worn (2.5/24 h) than in wearable surface devices (.96/24 h). Three of the 23 studies also detected PNES; the mean sensitivity and FAR from these studies were 62.9% and .79/24 h, respectively. Four studies detected both focal and tonic-clonic seizures, and one study detected focal seizures only; the sensitivities ranged from 31.1% to 93.1% in these studies. SIGNIFICANCE: Reported noninvasive wearable devices had high sensitivity but relatively high FARs in detecting tonic-clonic seizures during limited recording time in a video-EEG setting. Future studies should focus on reducing FAR, detection of other seizure types and PNES, and longer recording in the community.

A retrospective study of the correlation between duration of monitoring in the epilepsy monitoring unit and diagnostic yield.

OBJECTIVE: Long-term video-electroencephalographic (LTVEM) monitoring is a valuable tool in the evaluation of paroxysmal clinical events. However, vEEG itself is costly. Hence, we aimed to establish if longer duration of monitoring (DOM) is associated with higher diagnostic yield. METHOD: A retrospective review of patients admitted into the epilepsy monitoring unit (EMU) for the diagnostic evaluation of paroxysmal events was performed. Patients' demographic, clinical characteristics, and vEEG data were analyzed. In the cohort of patients with DOM > 7 days, the reasons for prolonged DOM were identified and the differences in clinical characteristics and vEEG data between conclusive and inconclusive studies were analyzed. RESULT: A total of 501 patients were included. Four hundred and thirty-six (87 %) patients had conclusive studies. Of these patients, 67.9 % patients with conclusive studies received diagnosis within the first 7 days of monitoring with the highest on day 7. The likelihood of conclusive studies decreased beyond 7 days. A total of 175 had DOM > 7 days, of which 140 (80 %) had conclusive studies. In the cohort with DOM > 7 days, patients with previous abnormal routine EEG, previous vEEG monitoring, first event recorded before day 5 of admission and ≥1 events recorded during vEEG monitoring were more likely to have conclusive studies. The most common reason for prolonging DOM beyond 7 days was to adequately record multiple semiologically distinctive events (76 %). CONCLUSION: Our study supports that longer DOM is associated with an increase in diagnostic yield. More than one-third of our cohort were monitored beyond 7 days with majority (80 %) being conclusive. Our findings may guide clinicians in planning the DOM and predicting the likelihood of conclusive vEEG studies in patients with prolonged DOM based on the clinical characteristics and vEEG data.

Semiologic differences between bilateral tonic-clonic seizures of focal onset and generalized onset.

BACKGROUND: Focal semiologies have been described in idiopathic generalized epilepsies (IGE) and generalized-onset bilateral tonic-clonic seizures (GBTCS). These focal signs may lead to wrong diagnosis and inappropriate choice of antiseizure medications. We sought to investigate the differences in focal semiologic features between GBTCS and focal-onset bilateral tonic-clonic seizures (FBTCS). METHODS: We retrospectively reviewed video-EEG data of captured GBTCS and FBTCS over a period of five years. The presence or absence of 12 focal signs as well seizure duration and time to head version was tabulated for each seizure. We used the chi-square test for independence and Fisher's exact test to investigate the occurrence of each focal sign in FBTCS compared with GBTCS. Additionally, we used receiver operating characteristic (ROC) curves to explore if the seizure duration and time to head version from the ictal onset can reliably differentiate between FBTCS and GBTCS. Finally, we employed hierarchical cluster analysis to visualize how these focal signs appear in combination. RESULTS: Head version (p <.001), preceding automatisms (p <.001), eye version (p <.001), unilateral facial clonic activity (p <.001), and mouth deviation (p =.004) were found to be significantly more frequent in FBTCS. Longer seizures were highly in favor of FBTCS whereas shorter time to head version from the ictal onset indicated GBTCS in the ROC curve analysis. CONCLUSIONS: Though focal signs occur in GBTCS, careful evaluation of semiology can help the clinician distinguish FBTCS from GBTCS.

Factors associated with comorbid epilepsy in patients with psychogenic nonepileptic seizures: A large cohort study.

OBJECTIVE: Comorbid epilepsy and psychogenic nonepileptic seizures (PNES) occur in 12-22% of cases and the diagnosis of both simultaneous disorders is challenging. We aimed to identify baseline characteristics that may help distinguish patients with PNES-only from those with comorbid epilepsy. METHODS: We performed a longitudinal cohort study on those patients diagnosed with PNES in our epilepsy monitoring unit (EMU) between May 2001 and February 2011, prospectively followed up until September 2016. Patients were classified into PNES-only, PNES + possible or probable epilepsy, and PNES + definite epilepsy based on the clinical, vEEG, and neuroimaging data. Demographic and basal clinical data were obtained from chart review. Multiple regression models were performed to identify significant predictors of PNES + definite epilepsy, excluding patients with only possible or probable epilepsy for this specific analysis. RESULTS: One-hundred and ninety four patients with PNES-only, 30 with PNES + possible or probable epilepsy and 47 with PNES + definite epilepsy were included. 73.8% were female and the mean age at EMU admission was 37.4 ±â€¯standard deviation 13.5 years. Patients with PNES + definite epilepsy most likely had never worked, had history of febrile seizures, structural brain lesions, developmental disabilities, and maximum reported seizure duration between 0.5 and 2 min. Patients with PNES-only were on fewer anti-seizure medications (ASM), reported more frequently an initial minor head trauma, seizures longer than 10 min, and a higher number of neurological and medical illnesses - being migraine (18.1%), other types of headaches (18.5%), and asthma (15.5%) the most prevalent ones. All p < 0.05. On the hierarchical regression analysis, history of febrile seizures, developmental disabilities, brain lesions, longest reported seizure duration between 0.5 and 2 min, and lack of neurological comorbidity, remained as significant predictors of PNES + epilepsy. The model's performance of a 5-fold cross-validation analysis showed an overall accuracy of 84.7% to classify patients correctly. CONCLUSIONS: Some demographic and clinical characteristics may support the presence of comorbid epilepsy in patients with PNES, being unemployment, the presence of brain lesions, developmental disabilities, history of febrile seizures, seizure duration and lack of comorbid headaches the most relevant ones.

Duration of postictal impaired awareness after bilateral tonic-clonic seizures: EEG and patient characteristics.

OBJECTIVE: Ictal and postictal phenomena that may impact the duration of postictal impaired awareness have not been well studied. Postictal unresponsiveness invariably occurs following bilateral tonic-clonic seizures (BTCS). Bilateral tonic-clonic seizures are a major risk factor for sudden unexpected death in epilepsy (SUDEP). We quantify the effects of seizure characteristics on postictal recovery of awareness following BTCS. Factors include: the total seizure duration, the duration of the tonic phase of a BTCS, presence of postictal generalized EEG suppression (PGES), duration of postictal tonic electromyographic discharge, peri-ictal respiratory dysfunction, patient age, duration of epilepsy, and gender. METHODS: Fifty-eight patients admitted to the epilepsy monitoring unit with BTCS were studied. Forty-one had unilateral onset temporal seizures. The remainder had bitemporal onsets, extratemporal onsets, undetermined onsets, or were generalized at onset. Following the first BTCS, time to initial recovery of awareness and its possible association with patient and seizure characteristics as well as peri-ictal respiratory dysfunction were evaluated. The presence or absence of postictal agitation was noted. RESULTS: The severity of respiratory dysfunction and seizure characteristics were not associated with time to initial recovery of awareness. A shorter time to recovery of awareness was significantly associated with a younger age (p = 0.007). Postictal agitation was more common in males (p = 0.023). SIGNIFICANCE: Focal seizures may impair awareness by active inhibition of subcortical arousal mechanisms. Focal seizures progressing to bilateral tonic-clonic seizures (BTCS) result in further widespread cerebral dysfunction impacting postictal awareness. MRI studies show accelerated brain aging in patients with temporal lobe epilepsy. Our findings suggest that patient age, as a surrogate marker for the lifetime burden of seizures, results in a progressive worsening in time to recovery after BTCS by an increasing negative impact on networks involved in arousal.