Duration of epileptic seizure types: A data-driven approach.

OBJECTIVE: To determine the duration of epileptic seizure types in patients who did not undergo withdrawal of antiseizure medication. METHODS: From a large, structured database of 11 919 consecutive, routine video-electroencephalograpy (EEG) recordings, labeled using the SCORE (Standardized Computer-Based Organized Reporting of EEG) system, we extracted and analyzed 2742 seizures. For each seizure type we determined median duration and range after removal of outliers (2.5-97.5 percentile). We used surface electromyography (EMG) for accurate measurement of short motor seizures. RESULTS: Myoclonic seizures last <150 ms, epileptic spasms 0.4-2 s, tonic seizures 1.5-36 s, atonic seizures 0.1-12,5 s, when measured using surface EMG. Generalized clonic seizures last 1-24 s. Typical absence seizures are rarely longer than 30 s (2.75-26.5 s) and atypical absences last 2-100 s. In our patients, the duration of focal aware (median: 27 s; 1.25-166 s) and impaired awareness seizures (median: 42.5 s; 9.5-271 s) was shorter than reported previously in patients undergoing withdrawal of antiseizure medication. All focal seizures terminated within 10 min. Median duration of generalized tonic-clonic seizures was 79.5 s (57-102 s) and of focal-to-bilateral tonic-clonic seizures was 103.5 (77.5-237 s). All tonic-clonic seizures terminated within 5 min. SIGNIFICANCE: This comprehensive list of seizure durations provides important information for characterizing seizures and diagnosing patients with epilepsy. The upper limits of seizure durations are helpful in early recognition of imminent status epilepticus.

Semiautomated classification of nocturnal seizures using video recordings.

OBJECTIVE: The objective of this study was to evaluate the accuracy of a semiautomated classification of nocturnal seizures using a hybrid system consisting of an artificial intelligence-based algorithm, which selects epochs with potential clinical relevance to be reviewed by human experts. METHODS: Consecutive patients with nocturnal motor seizures admitted for video-electroencephalographic long-term monitoring (LTM) were prospectively recruited. We determined the extent of data reduction by using the algorithm, and we evaluated the accuracy of seizure classification from the hybrid system compared with the gold standard of LTM. RESULTS: Forty consecutive patients (24 male; median age = 15 years) were analyzed. The algorithm reduced the duration of epochs to be reviewed to 14% of the total recording time (1874 h). There was a fair agreement beyond chance in seizure classification between the hybrid system and the gold standard (agreement coefficient = .33, 95% confidence interval = .20-.47). The hybrid system correctly identified all tonic-clonic and clonic seizures and 82% of focal motor seizures. However, there was low accuracy in identifying seizure types with more discrete or subtle motor phenomena. SIGNIFICANCE: Using a hybrid (algorithm-human) system for reviewing nocturnal video recordings significantly decreased the workload and provided accurate classification of major motor seizures (tonic-clonic, clonic, and focal motor seizures).

Seizure provocation in EEG recordings: A data-driven approach.

OBJECTIVE: Recording seizures on video-EEG has a high diagnostic value. However, bilateral convulsive seizures constitute a risk for the patients. Our aim was to investigate the diagnostic yield and associated risks of provocation methods in short-term video-EEGs. METHODS: We extracted data on seizures and provocation methods from a large database of short-term video-EEGs with standardized annotations using SCORE (Standardized Computer-based Organized reporting of EEG). RESULTS: 2742 paroxysmal clinical episodes were recorded in 11 919 consecutive EEGs. Most epileptic seizures (54%) were provoked. Hyperventilation provoked most of typical absence seizures (55%), intermittent photic stimulation (IPS) provoked myoclonic seizures (25%) and most of bilateral convulsive seizures (55%), while 43% of focal seizures were precipitated by sleep. All but one of the 16 bilateral convulsive seizures were provoked by IPS or sleep. Latency between start of generalized photoparoxysmal EEG response and bilateral convulsive seizures were ≤3 s in all but one patient. SIGNIFICANCE: The large, structured database provides evidence for the diagnostic utility of various provocation methods in short-term video-EEGs. The risk of bilateral convulsive seizures is relatively small, but it cannot be prevented by stopping IPS after 3 s. A priori knowledge about seizure semiology helps planning patient-tailored provocation strategy in short-term video-EEGs.

Automated analysis and detection of epileptic seizures in video recordings using artificial intelligence.

Introduction: Automated seizure detection promises to aid in the prevention of SUDEP and improve the quality of care by assisting in epilepsy diagnosis and treatment adjustment. Methods: In this phase 2 exploratory study, the performance of a contactless, marker-free, video-based motor seizure detection system is assessed, considering video recordings of patients (age 0-80 years), in terms of sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves, with respect to video-electroencephalographic monitoring (VEM) as the medical gold standard. Detection performances of five categories of motor epileptic seizures (tonic-clonic, hyperkinetic, tonic, unclassified motor, automatisms) and psychogenic non-epileptic seizures (PNES) with a motor behavioral component lasting for >10 s were assessed independently at different detection thresholds (rather than as a categorical classification problem). A total of 230 patients were recruited in the study, of which 334 in-scope (>10 s) motor seizures (out of 1,114 total seizures) were identified by VEM reported from 81 patients. We analyzed both daytime and nocturnal recordings. The control threshold was evaluated at a range of values to compare the sensitivity (n = 81 subjects with seizures) and false detection rate (FDR) (n = all 230 subjects). Results: At optimal thresholds, the performance of seizure groups in terms of sensitivity (CI) and FDR/h (CI): tonic-clonic- 95.2% (82.4, 100%); 0.09 (0.077, 0.103), hyperkinetic- 92.9% (68.5, 98.7%); 0.64 (0.59, 0.69), tonic- 78.3% (64.4, 87.7%); 5.87 (5.51, 6.23), automatism- 86.7% (73.5, 97.7%); 3.34 (3.12, 3.58), unclassified motor seizures- 78% (65.4, 90.4%); 4.81 (4.50, 5.14), and PNES- 97.7% (97.7, 100%); 1.73 (1.61, 1.86). A generic threshold recommended for all motor seizures under study asserted 88% sensitivity and 6.48 FDR/h. Discussion: These results indicate an achievable performance for major motor seizure detection that is clinically applicable for use as a seizure screening solution in diagnostic workflows.

EEG normal variants: A prospective study using the SCORE system.

Objective: To determine the prevalence and characteristics of normal variants in EEG recordings in a large cohort, and provide readers with typical examples of all normal variants for educational purposes. Methods: Using the SCORE EEG system (Standardized Computer-Based Organized Reporting of EEG), we prospectively extracted EEG features in consecutive patients. In this dataset, we analyzed 3050 recordings from 2319 patients (mean age 38.5 years; range: 1-89 years). Results: The distribution of the normal variants was as follows: sharp transients 19.21% (including wicket spikes), rhythmic temporal theta of drowsiness 6.03%, temporal slowing of the old 2.89%, slow fused transients 2.59%, 14-and 6-Hz bursts 1.83%, breach rhythm 1.25%, small sharp spikes 1.05%, 6-Hz spike and slow wave 0.69% and SREDA 0.03%. Conclusions: The most prevalent normal variants are the sharp transients, which must not be over-read as epileptiform discharges. Significance: EEG readers must be familiar with the normal variants to avoid misdiagnosis and misclassification of patients referred to clinical EEG recordings.

Automated detection of nocturnal motor seizures using an audio-video system.

BACKGROUND: Unsupervised nocturnal tonic-clonic seizures (TCSs) may lead to sudden unexpected death in epilepsy (SUDEP). Major motor seizures (TCSs and hypermotor seizures) may lead to injuries. Our goal was to develop and validate an automated audio-video system for the real-time detection of major nocturnal motor seizures. METHODS: In this Phase-3 clinical validation study, we assessed the performance of automated detection of nocturnal motor seizures using audio-video streaming, computer vision and an artificial intelligence-based algorithm (Nelli). The detection threshold was predefined, the validation dataset was independent from the training dataset, patients were prospectively recruited, and the analysis was performed in real time. The gold standard was based on expert evaluation of long-term video electroencephalography (EEG). The primary outcome was the detection of nocturnal major motor seizures (TCSs and hypermotor seizures). The secondary outcome was the detection of other (minor) nocturnal motor seizures. RESULTS: We recruited 191 participants aged 1-72 years (median: 20 years), and we monitored them for 4183 h during the night. Device deficiency was present 10.5% of the time. Fifty-one patients had nocturnal motor seizures during the recording. The sensitivity for the major motor seizures was 93.7% (95% confidence interval: 69.8%-99.8%). The system detected all 11 TCS and four out of five (80%) hypermotor seizures. For the minor motor seizure types, the sensitivity was low (8.3%). The false detection rate was 0.16 per h. CONCLUSION: The Nelli system detects nocturnal major motor seizures with a high sensitivity and is suitable for implementation in institutions (hospitals, residential care facilities), where rapid interventions triggered by alarms can potentially reduce the risk of SUDEP and injuries.

Photoparoxysmal response and its characteristics in a large EEG database using the SCORE system.

OBJECTIVE: To characterize photoparoxysmal EEG response (PPR) using a standardized protocol of intermittent photic stimulation (IPS) and standardized definitions for PPR, classified into six types. METHODS: Using the SCORE system (Standardized Computer-Based Organized Reporting of EEG) we prospectively built a large database of standardized EEG annotations. In this study, we extracted the features related to PPR from the structured dataset consisting of 10,671 EEG recordings with IPS, from 7,188 patients. RESULTS: The standardized IPS protocol elicited PPR in 375 recordings (3.5%), in 288 patients (4%), with a preponderance among young (11-20 years) and female patients (67%). PPR was persistent in patients with multiple recordings. The most frequent type of PPR was activation of preexisting epileptogenic area (58%), followed by generalized-PPR limited to the stimulus train (22%). We could not find any recording with self-sustained posterior response. Seizures were elicited in 27% of patients with PPR, most often myoclonic seizures and absences, in patients with self-sustained generalized PPR. CONCLUSIONS: The most common type of PPR was accentuation of preexisting epileptogenic area. Self-sustained posterior response could not be documented. Self-sustained generalized-PPR had the highest association with seizures. SIGNIFICANCE: Using standardized stimulation protocol and definitions for PPR types, IPS provides high diagnostic yield.

Modulation in time of the interictal spiking pattern related to epileptic seizures.

OBJECTIVE: To test the hypothesis that significant changes in the occurrence of interictal epileptiform electroencephalography (EEG) discharges (EDs) are associated with seizures: while some EDs are pro-convulsive, increasing at seizure-occurrence, others are protective, showing decrease related to seizures. METHODS: We analyzed 102 consecutive, long-term video-EEG monitoring sessions, from 98 patients. Using a semi-automated spike-detection method, we quantified the occurrence of EDs, grouped according to their location and morphology (clusters) and we constructed graphical representation of data, showing changes in time of the spiking patterns (spike-histograms). We compared the spike-histograms with the time-points of the seizures (pre-, peri- and postictal changes). RESULTS: Totally 179 ED-clusters were identified. Modulation of the spiking pattern, associated with seizures, was observed in 66 clusters (37%), from 47 patients (48%). Most of these changes (40 clusters; 61%) were related to increase in the spiking-pattern. CONCLUSIONS: Changes in spiking-pattern were associated with more than one third of the EDs. Both increasing and decreasing patterns were observed. SIGNIFICANCE: EDs are more often pro-convulsive, with increasing spiking patterns associated with seizures. However, in more than one third of the ED clusters modulated by seizures, the spiking pattern decreased, raising the possibility of an anticonvulsive function of these discharges.

REM-sleep related hypermotor seizures: Video documentation and ictal source imaging.

INTRODUCTION: Rapid eye movement (REM) sleep has an inhibitory effect on epileptiform EEG discharges, and seizures occur extremely rarely in REM sleep. CASE STUDY: We present the case and video recordings of a 10-year-old boy, with sleep-related hypermotor seizures starting from REM sleep, identified from videoEEG recordings. The semiology comprised intense fear, tachycardia, tachypnea, followed by hypermotor manifestations. Further investigations included brain MRI and source localization of the EEG signals. Multiple antiepileptic drugs were tried, the patient obtaining a good control of the seizures in the last 2.5 years with eslicarbazepine. DISCUSSION AND CONCLUSION: The ictal EEG source imaging showed seizure onset in the anterior part of the right insula, with propagation to the orbitofrontal area, confirmed by the semiological sequence. Although rare, focal seizures can be triggered by REM sleep and our findings suggest that deficient maturation of brain areas involved in sleep modulation might induce insufficient desynchronization during REM sleep, thus allowing seizure emergence.

Increasing human brain excitability by transcranial high-frequency random noise stimulation.

For >20 years, noninvasive transcranial stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS) have been used to induce neuroplastic-like effects in the human cortex, leading to the activity-dependent modification of synaptic transmission. Here, we introduce a novel method of electrical stimulation: transcranial random noise stimulation (tRNS), whereby a random electrical oscillation spectrum is applied over the motor cortex. tRNS induces consistent excitability increases lasting 60 min after stimulation. These effects have been observed in 80 subjects through both physiological measures and behavioral tasks. Higher frequencies (100-640 Hz) appear to be responsible for generating this excitability increase, an effect that may be attributed to the repeated opening of Na(+) channels. In terms of efficacy tRNS appears to possess at least the same therapeutic potential as rTMS/tDCS in diseases such as depression, while furthermore avoiding the constraint of current flow direction sensitivity characteristic of tDCS.

Diagnostic yield of standard-wake and sleep EEG recordings.

OBJECTIVE: To investigate whether Posterior Dominant Rhythm (PDR) can be reliably assessed in sleep-EEG recordings and to investigate the diagnostic yield of standard-wake and sleep-recordings. METHODS: EEG recordings of 303 consecutive patients aged 18-88 years were analyzed. All patients had both standard-wake and sleep-recordings, including patients who had abnormal standard recordings. Melatonin was used in 6% of sleep EEGs, and sleep deprivation in 94%. The mean duration of sleep was 41 min. We measured the PDR frequency in standard and sleep-recordings, both before and after sleep. We compared the diagnostic yield of standard-wake and sleep EEG recordings. RESULTS: Compared to standard EEG, sleep-recordings showed a significantly lower PDR frequency, both when measured before and after sleep (p < 0.001). One-hundred-fifty-six patients (51%) had normal standard recordings, and 35 of them (22%) had abnormal findings in the sleep-recording. One-hundred-forty-seven patients had abnormal standard recordings and in 16 of them (11%) these abnormalities were not present in sleep-recording. CONCLUSIONS: PDR is significantly slower in the wake periods of sleep-recordings, compared to standard wake recordings. SIGNIFICANCE: Sleep and standard wake recordings are complementary.

Added clinical value of the inferior temporal EEG electrode chain.

OBJECTIVE: To investigate the diagnostic added value of supplementing the 10-20 EEG array with six electrodes in the inferior temporal chain. METHODS: EEGs were recorded with 25 electrodes: 19 positions of the 10-20 system, and six additional electrodes in the inferior temporal chain (F9/10, T9/10, P9/10). Five-hundred consecutive standard and sleep EEG recordings were reviewed using the 10-20 array and the extended array. We identified the recordings with EEG abnormalities that had peak negativities at the inferior temporal electrodes, and those that only were visible at the inferior temporal electrodes. RESULTS: From the 286 abnormal recordings, the peak negativity was at the inferior temporal electrodes in 81 cases (28.3%) and only visible at the inferior temporal electrodes in eight cases (2.8%). In the sub-group of patients with temporal abnormalities (n = 134), these represented 59% (peak in the inferior chain) and 6% (only seen at the inferior chain). CONCLUSIONS: Adding six electrodes in the inferior temporal electrode chain to the 10-20 array improves the localization and identification of EEG abnormalities, especially those located in the temporal region. SIGNIFICANCE: Our results suggest that inferior temporal electrodes should be added to the EEG array, to increase the diagnostic yield of the recordings.

Influence of Concurrent Finger Movements on Transcranial Direct Current Stimulation (tDCS)-Induced Aftereffects.

Transcranial direct current stimulation (tDCS) has been reported to have bidirectional influence on the amplitude of motor-evoked potentials (MEPs) in resting participants in a polarity-specific manner: anodal tDCS increased and cathodal tDCS decreased them. More recently, the effects of tDCS have been shown to depend on a number of additional factors. We investigated whether a small variety of movements involving target and non-target muscles could differentially modify the efficacy of tDCS. MEPs were elicited from the right first dorsal interosseous muscle, defined as the target muscle, by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). During M1 tDCS, which lasted for 10 min applying anodal, cathodal, or sham condition, the participants were instructed to squeeze a ball with their right hand (Task 1), to move their right index finger only in the medial (Task 2), in the lateral direction (Task 3), or in medial and lateral direction alternatively (Task 4). Anodal tDCS reduced MEP amplitudes measured in Task 1 and Task 2, but to a lesser extent in the latter. In Task 3, anodal tDCS led to greater MEP amplitudes than cathodal stimulation. Alternating movements resulted in no effect of tDCS on MEP amplitude (Task 4). The results are congruent with the current notion that the aftereffects of tDCS are highly variable relying on a number of factors including the type of movements executed during stimulation.

Do patients need to stay in bed all day in the Epilepsy Monitoring Unit? Safety data from a non-restrictive setting.

PURPOSE: To assess whether injuries occur more often in an Epilepsy Monitoring Unit (EMU) where portable EEG amplifiers are used, and where patients can freely move within a large area during the monitoring. METHODS: Patients were monitored at the Danish Epilepsy Center, in an EMU specifically designed for this purpose, and they were under continuous surveillance by personnel dedicated to the EMU. Adverse events (AEs) - including injuries, were prospectively noted, as part of the safety policy of the hospital. Other data were retrospectively extracted from the electronic database, for a 5-year period (January 2012-December 2016). RESULTS: 976 patients were admitted to the EMU. Falls occurred in 19 patients (1.9%) but none of them resulted in injury. Only one serious AE occurred: a patient had a convulsive status epilepticus, which did not respond to first-line treatment in the EMU and was transferred to the intensive care unit. The rate of AEs were similar or lower than previously reported by other centers, where the mobility of the patients had been restricted during monitoring. CONCLUSION: In an EMU specially designed for this purpose, where patients are under continuous surveillance by personnel dedicated to the EMU, injuries can be avoided even when the mobility of the patients is not restricted.

Standardized computer-based organized reporting of EEG: SCORE - Second version.

Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.

The effect of sleep deprivation on median nerve somatosensory evoked potentials.

The purpose of the study was to determine the effect of one night's sleep deprivation on the early and middle-latency median nerve (MN) somatosensory evoked potentials (SEPs). In 20 healthy volunteers, SEPs in response to electrical stimulation of the MN at the wrist were recorded for the 100-ms post-stimulus period, before and after one night of sleep deprivation. The P14 latency was significantly prolonged after sleep deprivation. We found significant increases in the amplitudes of the early parietal (N20-P24) and the frontal middle-latency (P45-N60) components following sleep deprivation. Our results indicate that somatosensory processing is altered after sleep deprivation.

Diagnostic yield of five minutes compared to three minutes hyperventilation during electroencephalography.

PURPOSE: To investigate whether hyperventilation (HV) for 5min increases the diagnostic yield of electroencephalography (EEG) compared to 3min HV. METHODS: data were evaluated from 1084 consecutive patients, from three European centres, referred to EEG on suspicion of epilepsy. Seizures and interictal EEG abnormalities precipitated during the first 3min and during the last 2min of the HV period (totally 5min) were determined. RESULTS: Eight hundred seventy-seven patients (81%) completed 5min HV. Seizures were precipitated during the first 3min of HV in 21 patients, and during the last 2min in four more patients. Interictal EEG abnormalities were precipitated in the first 3min of HV in 16 patients, and during the last 2min in 7 more patients. Psychogenic nonepileptic seizures occurred in eight patients during the first 3min of HV and in two more patients during the last 2min. No adverse events occurred during the last 2min of HV, but eight patients (1%) stopped HV during the last 2min because they were not able to hyperventilate further. CONCLUSION: 16% of seizures and 30% of interictal EEG abnormalities triggered by HV occurred during the last 2min of HV, suggesting the clinical usefulness of prolonged hyperventilation for 5min. The vast majority of patients (99%) who are able to hyperventilate for 3min can complete 5min HV, without additional adverse events.

Minocycline exerts acute inhibitory effects on cerebral cortex excitability in humans.

Minocycline has efficacy to alleviate seizure activity in animal models of epilepsy. Among other mechanisms it has been postulated that minocycline can inhibit microglial activation and develop beneficial effects by decreasing glutamate excitotoxicity. To explore acute effects of minocycline on human motor cortex excitability we used single- and paired-pulse transcranial magnetic stimulation in 12 healthy subjects 4h after a single oral dose of 200mg minocycline or placebo was administered in a randomised, double-blind, placebo-controlled crossover design. Mean cortical silent period, an inhibitory parameter of predominantly intracortical origin, was prolonged after minocycline compared to placebo, while other TMS parameters of cortical excitability remained unchanged. The results demonstrate that a particular parameter of cortical inhibition is rapidly increased after a single oral dose of minocycline in humans.