Redefined giant somatosensory evoked potentials: Evoked epileptic complexes of excitatory and inhibitory components.

OBJECTIVE: Giant somatosensory evoked potentials (SEPs) are observed in patients with cortical myoclonus. Short-latency components (SLC), are regarded as evoked epileptic activities or paroxysmal depolarization shifts (PDSs). This study aimed to reveal the electrophysiological significance of the middle-latency component (MLC) P50 of the SEPs. METHODS: Twenty-two patients with cortical myoclonus having giant SEPs (patient group) and 15 healthy controls were included in this study. Waveform changes in SEPs before and after perampanel (PER) treatment were evaluated in the patient group. The wide range, time-frequency properties underlying the waveforms were compared between the groups. RESULTS: After PER treatment, SLC was prolonged and positively correlated with PER concentration, whereas MLC showed no correlation with PER concentration. Time-frequency analysis showed a power increase (156 Hz in all patients, 624 Hz in benign adult familial myoclonus epilepsy patients) underlying SLC and a power decrease (156 Hz, 624 Hz) underlying MLC in the patient group. CONCLUSIONS: The high-frequency power increase in SLCs and decrease in MLCs clearly reflected PDS and subsequent hyperpolarization, respectively. This relationship was similar to that of interictal epileptiform discharges, suggesting that giant SEPs evoke epileptic complexes of excitatory and inhibitory components. SIGNIFICANCE: MLCs of giant SEPs reflected inhibitory components.

Specific consistency score for rational selection of epilepsy resection surgery candidates.

OBJECTIVE: Degree of indication for epilepsy surgery is determined by taking multiple factors into account. This study aimed to investigate the usefulness of the Specific Consistency Score (SCS), a proposed score for focal epilepsy to rate the indication for epilepsy focal resection. METHODS: This retrospective cohort study included patients considered for resective epilepsy surgery in Kyoto University Hospital from 2011 to 2022. Plausible epileptic focus was tentatively defined. Cardinal findings were scored based on specificity and consistency with the estimated laterality and lobe. The total points represented SCS. The association between SCS and the following clinical parameters was assessed by univariate and multivariate analysis: (1) probability of undergoing resective epilepsy surgery, (2) good postoperative seizure outcome (Engel I and II or Engel I only), and (3) lobar concordance between the noninvasively estimated focus and intracranial electroencephalographic (EEG) recordings. RESULTS: A total of 131 patients were evaluated. Univariate analysis revealed higher SCS in the (1) epilepsy surgery group (8.4 [95% confidence interval (CI) = 7.8-8.9] vs. 4.9 [95% CI = 4.3-5.5] points; p < .001), (2) good postoperative seizure outcome group (Engel I and II; 8.7 [95% CI = 8.2-9.3] vs. 6.4 [95% CI = 4.5-8.3] points; p = .008), and (3) patients whose focus defined by intracranial EEG matched the noninvasively estimated focus (8.3 [95% CI = 7.3-9.2] vs. 5.4 [95% CI = 3.5-7.3] points; p = .004). Multivariate analysis revealed areas under the curve of .843, .825, and .881 for Parameters 1, 2, and 3, respectively. SIGNIFICANCE: SCS provides a reliable index of good indication for resective epilepsy surgery and can be easily available in many institutions not necessarily specializing in epilepsy.

[A case of Alice in Wonderland syndrome after Epstein-Barr virus (EBV) encephalitis: a mimicry of focal epileptic seizure].

A 30-year-old man who received infliximab for treatment of Crohn's disease developed Epstein-Barr virus (EBV) encephalitis, which responded well to therapy; however, he had left lower visual field loss following treatment. The patient noticed peculiar symptoms 9 months after recovery from encephalitis; objects in his view appeared smaller or larger than their actual size (micropsia/macropsia). Moreover, it appeared that objects outside moved faster or slower than their actual speed of movements and moving objects appeared as a series of many consecutive snap shots. His vision was blurred, and he had visual difficulties and a sensation that his body was floating. These symptoms mainly appeared following fatigue and persisted over approximately 10 years. Based on cerebrospinal fluid analysis, brain MRI, N-isopropyl-p-123I-iodoamphetamine with single photon emission computed tomography, fluorodeoxyglucose positron emission tomography, and electroencephalography, we excluded both recurrent encephalitis and focal epileptic seizures. By taking all symptoms and other evaluation findings into account, the patient most likely suffered from "Alice in Wonderland syndrome" which is primarily associated with cortical dysfunction in the right temporo-parieto-occipital area as the consequence of previous acute EBV encephalitis.

Correlation between brain functional connectivity and neurocognitive function in patients with left frontal glioma.

The association between neurocognitive function (NCF) impairment and brain cortical functional connectivity in glioma patients remains unclear. The correlations between brain oscillatory activity or functional connectivity and NCF measured by the Wechsler Adult Intelligence Scale full-scale intelligence quotient scores (WAIS FSIQ), the Wechsler Memory Scale-revised general memory scores (WMS-R GM), and the Western aphasia battery aphasia quotient scores (WAB AQ) were evaluated in 18 patients with left frontal glioma using resting-state electroencephalography (EEG). Current source density (CSD) and lagged phase synchronization (LPS) were analyzed using exact low-resolution electromagnetic tomography (eLORETA). Although 2 and 2 patients scored in the borderline range of WAIS FSIQ and WMS-R GM, respectively, the mean WAIS FSIQ, WMS-R GM, and WAB AQ values of all patients were within normal limits, and none had aphasia. In the correlation analysis, lower WMS-R GM was associated with a higher LPS value between the right anterior prefrontal cortex and the left superior parietal lobule in the beta1 band (13-20 Hz, R = - 0.802, P = 0.012). These findings suggest that LPS evaluated by scalp EEG is associated with memory function in patients with left frontal glioma and mild NCF disorders.

Ictal direct current shifts contribute to defining the core ictal focus in epilepsy surgery.

Identifying the minimal and optimal epileptogenic area to resect and cure is the goal of epilepsy surgery. To achieve this, EEG analysis is recognized as the most direct way to detect epileptogenic lesions from spatiotemporal perspectives. Although ictal direct-current shifts (below 1 Hz) and ictal high-frequency oscillations (above 80 Hz) have received increasing attention as good indicators that can add more specific information to the conventionally defined seizure-onset zone, large cohort studies on postoperative outcomes are still lacking. This work aimed to clarify whether this additional information, particularly ictal direct-current shifts which is assumed to reflect extracellular potassium concentration, really improve postoperative outcomes. To assess the usefulness in epilepsy surgery, we collected unique EEG data sets recorded with a longer time constant of 10 s using an alternate current amplifier. Sixty-one patients (15 with mesial temporal lobe epilepsy and 46 with neocortical epilepsy) who had undergone invasive presurgical evaluation for medically refractory seizures at five institutes in Japan were retrospectively enrolled in this study. Among intracranially implanted electrodes, the two core electrodes of both ictal direct-current shifts and ictal high-frequency oscillations were independently identified by board-certified clinicians based on unified methods. The occurrence patterns, such as their onset time, duration, and amplitude (power) were evaluated to extract the features of both ictal direct-current shifts and ictal high-frequency oscillations. Additionally, we examined whether the resection ratio of the core electrodes of ictal direct-current shifts and ictal high-frequency oscillations independently correlated with favourable outcomes. A total of 53 patients with 327 seizures were analyzed for wide-band EEG analysis, and 49 patients were analyzed for outcome analysis. Ictal direct-current shifts were detected in the seizure-onset zone more frequently than ictal high-frequency oscillations among both patients (92% versus 71%) and seizures (86% versus 62%). Additionally, ictal direct-current shifts significantly preceded ictal high-frequency oscillations in patients exhibiting both biomarkers, and ictal direct-current shifts occurred more frequently in neocortical epilepsy patients than in mesial temporal lobe epilepsy patients. Finally, although a low corresponding rate was observed for ictal direct-current shifts and ictal high-frequency oscillations (39%) at the electrode level, complete resection of the core area of ictal direct-current shifts significantly correlated with favourable outcomes, similar to ictal high-frequency oscillation outcomes. Our results provide a proof of concept that the independent significance of ictal direct-current shifts from ictal high-frequency oscillations should be considered as reliable biomarkers to achieve favourable outcomes in epilepsy surgery. Moreover, the different distribution of the core areas of ictal direct-current shifts and ictal high-frequency oscillations may provide new insights into the underlying mechanisms of epilepsy, in which not only neurons but also glial cells may be actively involved via extracellular potassium levels.

Corrigendum: A Long Time Constant May Endorse Sharp Waves and Spikes Over Sharp Transients in Scalp Electroencephalography: A Comparison of After-Slow Among Different Time Constants Concordant With High-Frequency Activity Analysis.

[This corrects the article DOI: 10.3389/fnhum.2021.748893.].

Two types of clinical ictal direct current shifts in invasive EEG of intractable focal epilepsy identified by waveform cluster analysis.

OBJECTIVE: To determine clinically ictal direct current (DC) shifts that can be identified by a time constant (TC) of 2 s and to delineate different types of DC shifts by different attenuation patterns between TC of 10 s and 2 s. METHODS: Twenty-one patients who underwent subdural electrode implantation for epilepsy surgery were investigated. For habitual seizures, we compared (1) the peak amplitude and (2) peak latency of the earliest ictal DC shifts between TC of 10 s and 2 s. Cluster and logistic regression analyses were performed based on the attenuation rate of amplitude and peak latency with TC 10 s. RESULTS: Ictal DC shifts in 120 seizures were analyzed; 89.1% of which were appropriately depicted even by a TC of 2 s. Cluster and logistic regression analyses revealed two types of ictal DC shift. Namely, a rapid development pattern was defined as the ictal DC shifts with a shorter peak latency and they also showed smaller attenuation rate of amplitude (73/120 seizures). Slow development pattern was defined as the ictal DC shifts with crosscurrent of a rapid development pattern, i.e., a longer peak latency and larger attenuation rate of amplitude (47/120 seizures). Focal cortical dysplasia (FCD) 1A tended to show a rapid development pattern (22/29 seizures) and FCD2A tended to show a slow development pattern (13 /18 seizures), indicating there might be some correlations between two types of ictal DC shift and certain pathologies. CONCLUSIONS: Ictal DC shifts, especially rapid development pattern, can be recorded and identified by the AC amplifiers of TC of 2 s which is widely used in many institutes compared to that of TC of 10 s. Two types of ictal DC shifts were identified with possibility of corresponding pathology. SIGNIFICANCE: Ictal DC shifts can be distinguished by their attenuation patterns.

Enhanced phase-amplitude coupling of human electrocorticography selectively in the posterior cortical region during rapid eye movement sleep.

The spatiotemporal dynamics of interaction between slow (delta or infraslow) waves and fast (gamma) activities during wakefulness and sleep are yet to be elucidated in human electrocorticography (ECoG). We evaluated phase-amplitude coupling (PAC), which reflects neuronal coding in information processing, using ECoG in 11 patients with intractable focal epilepsy. PAC was observed between slow waves of 0.5-0.6 Hz and gamma activities, not only during light sleep and slow-wave sleep (SWS) but even during wakefulness and rapid eye movement (REM) sleep. While PAC was high over a large region during SWS, it was stronger in the posterior cortical region around the temporoparietal junction than in the frontal cortical region during REM sleep. PAC tended to be higher in the posterior cortical region than in the frontal cortical region even during wakefulness. Our findings suggest that the posterior cortical region has a functional role in REM sleep and may contribute to the maintenance of the dreaming experience.

A Long Time Constant May Endorse Sharp Waves and Spikes Over Sharp Transients in Scalp Electroencephalography: A Comparison of After-Slow Among Different Time Constants Concordant With High-Frequency Activity Analysis.

Objective: To clarify whether long time constant (TC) is useful for detecting the after-slow activity of epileptiform discharges (EDs): sharp waves and spikes and for differentiating EDs from sharp transients (Sts). Methods: We employed 68 after-slow activities preceded by 32 EDs (26 sharp waves and six spikes) and 36 Sts from 52 patients with partial and generalized epilepsy (22 men, 30 women; mean age 39.08 ± 13.13 years) defined by visual inspection. High-frequency activity (HFA) associated with the apical component of EDs and Sts was also investigated to endorse two groups. After separating nine Sts that were labeled by visual inspection but did not fulfill the amplitude criteria for after-slow of Sts, 59 activities (32 EDs and 27 Sts) were analyzed about the total area of after-slow under three TCs (long: 2 s; conventional: 0.3 s; and short: 0.1 s). Results: Compared to Sts, HFA was found significantly more with the apical component of EDs (p < 0.05). The total area of after-slow in all 32 EDs under TC 2 s was significantly larger than those under TC 0.3 s and 0.1 s (p < 0.001). Conversely, no significant differences were observed in the same parameter of 27 Sts among the three different TCs. Regarding separated nine Sts, the total area of after-slow showed a similar tendency to that of 27 Sts under three different TCs. Significance: These results suggest that long TC could be useful for selectively endorsing after-slow of EDs and differentiating EDs from Sts. These findings are concordant with the results of the HFA analysis. Visual inspection is also equally good as the total area of after-slow analysis.

Dynamic theta/beta ratio of clinical EEG in Alzheimer's disease.

BACKGROUND: EEG of a resting state in Alzheimer disease (AD) patients and healthy controls (HC) are analyzed to identify the characteristics of EEG in AD. NEW METHOD: A dynamic box plot approach to the theta/beta ratio with various window durations is proposed to analyze EEG. RESULTS: Spectral results during a resting state in AD patients demonstrate the effect of relatively greater power in the low-frequency bands (i.e. 'slowing down' of the EEG). A significant difference is observed in the dynamic distribution of the theta/beta ratio in the AD and HC groups, which is related to the effect of 'slowing down'. There is a more obvious visual separation between the theta/beta ratio results for the AD and HC groups with increasing window durations. Variability of the theta/beta ratio can be observed with shorter window durations with a dynamic functional box plot. This provides a better classification accuracy by using the dynamic theta/beta ratio as a sensor to discriminate AD EEG from HC EEG by using the receiver operating characteristics (ROC) curve and the area under curve (AUC) with various window durations. COMPARISON WITH EXISTING METHOD(S): EEG spectral analysis and theta/beta ratio used to evaluate EEG typically rely on long time averaging. CONCLUSIONS: The dynamic box plot approach to the theta/beta ratio with various window durations provides the possibility of observing features of the EEG. The dynamic theta/beta ratio is a better sensor to discriminate AD EEG from HC EEG. Moreover, the reliability and accuracy of results can be increased by combining spectral analysis and the dynamic box plot approach to theta/beta ratio with various window durations.

A Biomarker for Benign Adult Familial Myoclonus Epilepsy: High-Frequency Activities in Giant Somatosensory Evoked Potentials.

BACKGROUND: Benign adult familial myoclonus epilepsy (BAFME) is one of the diseases that cause cortical myoclonus (CM) with giant somatosensory evoked potentials (SEPs). There are no useful diagnostic biomarkers differentiating BAFME from other CM diseases. OBJECTIVE: To establish reliable biomarkers including high-frequency oscillations (HFOs) with giant SEPs for the diagnosis of BAFME. METHODS: This retrospective case study included 49 consecutive CM patients (16 BAFME and 33 other CM patients) who exhibited giant P25 or N35 SEPs. SEPs were processed by a band-pass filter of 400-1000 Hz to analyze HFOs. Clinical and SEP findings were compared between (1) BAFME and other CM groups and (2) patients with presence and absence of P25-HFOs (HFOs superimposed on giant P25). The diagnostic power of each factor for BAFME was calculated. RESULTS: All 16 BAFME patients showed SEP P25-HFOs with significantly higher occurrence (P < 0.0001) compared with that of other CM groups. The presence of P25-HFOs significantly correlated with a BAFME diagnosis (P < 0.0001) and high SEP P25 and N35 amplitudes (P = 0.01 and P < 0.0001, respectively). BAFME was reliably diagnosed using P25-HFOs with high sensitivity (100%), specificity (87.9%), positive predictive value (80%), and negative predictive value (100%), demonstrating its superiority as a diagnostic factor compared to other factors. CONCLUSIONS: P25-HFOs with giant SEPs is a potential biomarker for BAFME diagnosis. P25-HFOs may reflect cortical hyperexcitability partly due to paroxysmal depolarizing shifts in epileptic neuronal activities and higher degrees of rhythmic tremulousness than those in ordinary CM. © 2021 International Parkinson and Movement Disorder Society.

[Scalp-recorded cortical spreading depolarizations (CSDs) of EEG with time constant of 2 seconds in a patient with acute traumatic brain injury].

An 82-year-old female suffered from head trauma, and developed acute consciousness disturbance 6 days after the event. Head CT showed the acute subdural hematoma in the left temporooccipital area and the patient underwent emergency hematoma evacuation and decompression. However, her consciousness disturbance became worse after surgery. Intermittent large negative infraslow shifts (lasting longer than 40 seconds) were recorded in the right posterior quadrant by scalp EEG with TC of 2 sec, that was defined as cortical spreading depolarizations (CSDs). Clinically consciousness disturbance sustained poor until 1 month after surgery in spite of treatment by anti-epileptic drugs. CSDs were observed on the right side where head injury most likely occurred. It may explain the sustained consciousness disturbance associated with significant prolonged ischemia. Once scalp EEG could record CSDs in this particular patient, the degree and its prognosis of traumatic head injury were estimated.

Electrical cortical stimulations modulate spike and post-spike slow-related high-frequency activities in human epileptic foci.

OBJECTIVE: Using interictal epileptiform discharges (IEDs), consisting of spikes and post-spike slow waves (PSSs), and IED-related high-frequency activities (HFAs), we elucidated inhibitory effects of electrical cortical stimulation (ECS) on human epileptic foci. METHODS: We recruited 8 patients with intractable focal epilepsy, and 50-Hz ECS was applied to the seizure-onset zone (SOZ) and non-SOZ. Before (5-min) and after (20-min) ECS, we evaluated the number of IED, the amplitudes of spikes and PSSs, spike-related HFA power, and PSS-related low gamma (30-50 Hz) activities. RESULTS: SOZ stimulation significantly decreased the number of IEDs and amplitude of spikes. Spike-related HFA power values in fast ripple (200-300 Hz) and ripple (80-150 Hz) bands were significantly suppressed only by SOZ stimulation in 4 and 3 patients, respectively. Among 4 patients with discrete PSSs, the amplitude ratio of spike/PSS decreased and the PSS-related low gamma activity power increased significantly in 2 patients and marginally in 1 patient. CONCLUSIONS: ECS potentially modulates cortical excitability by reducing excitation and increasing inhibition, and monitoring IED-related HFAs may help achieve the optimal effects of ECS. SIGNIFICANCE: IED and IED-related HFAs are dynamic, potential surrogate markers for epileptic excitability during the interictal period.

Scalp EEG Could Record Both Ictal Direct Current Shift and High-Frequency Oscillation Together Even With a Time Constant of 2 Seconds.

Herein, the authors report for the first time, scalp-recorded (1) focal ictal direct current (DC) shifts (active DC shifts; that precede conventional pattern) from the chronic focus of focal epilepsy and (2) ictal high-frequency oscillation after ictal DC shifts (passive DC shifts; that follow both conventional and high-frequency oscillation ictal patterns) from the acute focus of acute symptomatic seizures (Szs) in a 77-year-old man. Sixteen episodes of clinical Szs were recorded by scalp EEG with a 2-seconds time constant. Among the 16 recorded episodes of Sz, four EEG Sz patterns originated from the left posterior temporal area (chronic focus), and all patterns (100%) exhibited active DC shifts preceding the conventional pattern by 12 seconds. Twelve EEG Sz patterns originated from the right parietal area (acute focus), and the high-frequency oscillations (five Szs) (41.6%) and DC shifts (six Szs) (50%) occurred first, followed by the conventional pattern 8 seconds later. Because both the active and the passive DC shifts were recorded with a time constant of 2 seconds, which was smaller than that reported previously for ictal DC shifts (e.g., time constant of 10 seconds), clinically useful ictal DC shifts could be routinely inspected with a time constant of 2 seconds.

A score to map the lateral nonprimary motor area: Multispectrum intrinsic brain activity versus cortical stimulation.

OBJECTIVE: Multispectrum electrocorticographic components are critical for mapping the nonprimary motor area (NPMA). The objective of this study was to derive and validate a reliable scoring system for electrocorticography-based NPMA mapping (NPMA score) to replace electrical cortical stimulation (ECS) during brain surgery. METHODS: We analyzed 14 consecutive epilepsy patients with subdural electrodes implanted in the frontal lobe at Kyoto University Hospital. The NPMA score was retrospectively derived from multivariate analysis in the derivation group (patients = 7, electrodes = 713, during 2010-2013) and validated in the validation group (patients = 7, electrodes = 772, during 2014-2017). We assessed the accuracy and reliability of the score relative to ECS in determining the NPMA and predicting postoperative functional outcomes. RESULTS: Multivariate analysis in the derivation group led to an 8-point score for predicting ECS-based NPMA (1 point for anatomical localization of the electrode and 1 or 2 points for movement-related electrocorticographic components regardless of somatotopy in very slow cortical potential shifts [<0.5 Hz], 40-80-Hz band power increase, and 8-24-Hz band power decrease), which was validated in the validation group. The area under the receiver operating characteristic curve (AUC) was 0.89 in the derivation group. Good prediction (specificity = 94%, sensitivity = 100%) and discrimination (AUC = 0.87) were reproduced in the validation group. Overall, higher NPMA scores identified 2 patients with postoperative deficits after frontal lobe resection. SIGNIFICANCE: The NPMA score is reliable for NPMA mapping, potentially replacing ECS. It is a potential prognostic marker for postoperative functional deficits.

Low-dose perampanel improves refractory cortical myoclonus by the dispersed and suppressed paroxysmal depolarization shifts in the sensorimotor cortex.

OBJECTIVE: To elucidate the effects of perampanel (PER) on refractory cortical myoclonus for dose, etiology and somatosensory-evoked potential (SEP) findings. METHODS: We examined 18 epilepsy patients with seizure and cortical myoclonus. Based on data accumulated before and after PER treatment, correlations among clinical scores in myoclonus and activities of daily life (ADL); early cortical components of SEP; and PER blood concentration, were analyzed. RESULTS: PER (mean dose: 3.2 ±â€¯2.1 mg/day) significantly improved seizures, myoclonus and ADL and significantly decreased the amplitude of and prolonged latency of giant SEP components. The degree of P25 and N33 prolongations (23.8 ±â€¯1.6 to 24.7 ±â€¯1.7 ms and 32.1 ±â€¯4.0 to 33.7 ±â€¯3.4 ms) were significantly correlated with improved ADL score (p = 0.019 and p = 0.025) and blood PER concentration (p = 0.011 and p = 0.025), respectively. CONCLUSIONS: Low-dose PER markedly improved myoclonus and ADL in patients with refractory cortical myoclonus. Our results suggest that SEP, particularly P25 latency, can be used as a potential biomarker for assessing the objective effects of PER on intractable cortical myoclonus. SIGNIFICANCE: In this study, PER lessened the degree of synchronized discharges in the postsynaptic neurons in the primary motor cortex.