Seizures elicited by corneal 6-Hz stimulation are widely acknowledged as a model of temporal lobe seizures. Despite the intensive research in rodents, no studies hint at this model in developing animals. We focused on seven age groups of both male and female rats. Biphasic pulses with 0.3 ms duration and current intensities from 20 to 80 mA were applied transcorneally for 3 s to calculate threshold intensities for individual age groups. Threshold stimulation intensity necessary for elicitation of clonic seizures was highly age- and sex-dependent. The highest threshold was observed in the youngest (15-day-old) group then it decreased to the age of 25 days and increased again up to adulthood. The threshold current tended to be lower in females of all age groups. The incidence of convulsive seizures increased with stimulation intensity up to postnatal day 25 in either sex. In rats of 31 days old and older convulsions occurred irregularly regardless of the stimulation current and sex. For subsequent analysis, the animals were categorized into two groups: juveniles, aged 15 to 25 days, and adolescents/adults, aged 31 days and older. Our statistical analyses revealed an increased risk of convulsions after the stimulation with higher intensities in juvenile but not adolescent/adult rats. Females tended to be more sensitive to the stimulation with lower currents than males. Seizure severity was higher in females 18- to 25-day old compared to males of the same age and the seizure duration increased with stimulation intensities in juvenile but not adolescent/adult animals. The data extend the use of the rat 6 Hz model to immature animals and may be useful as a model of pediatric temporal lobe seizures.

• MeSH
• elektrická stimulace * MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• rohovka patofyziologie   patologie   MeSH
• věkové faktory MeSH
• záchvaty * patofyziologie   etiologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Ictal central apnoea is a feature of focal temporal seizures. It is implicated as a risk factor for sudden unexpected death in epilepsy (SUDEP). Here we study seizure-related apnoeas in two different models of experimental seizures, one chronic and one acute, in adult genetically-unmodified rats, to determine mechanisms of seizure-related apnoeas. Under general anaesthesia rats receive sensors for nasal temperature, hippocampal and/or neocortical potentials, and ECG or EMG for subsequent tethered video-telemetry. Tetanus neurotoxin (TeNT), injected into hippocampus during surgery, induces a chronic epileptic focus. Other implanted rats receive intraperitoneal pentylenetetrazol (PTZ) to evoke acute seizures. In chronically epileptic rats, convulsive seizures cause apnoeas (9.9 ± 5.3 s; 331 of 730 convulsive seizures in 15 rats), associated with bradyarrhythmias. Absence of EEG and ECG biomarkers exclude obstructive apnoeas. All eight TeNT-rats with diaphragm EMG have apnoeas with no evidence of obstruction, and have apnoea EMGs significantly closer to expiratory relaxation than inspiratory contraction during pre-apnoeic respiration, which we term "atonic diaphragm". Consistent with atonic diaphragm is that the pre-apnoeic nasal airflow is expiration, as it is in human ictal central apnoea. Two cases of rat sudden death occur. One, with telemetry to the end, reveals a lethal apnoea, the other only has video during the final days, which reveals cessation of breathing shortly after the last clonic epileptic movement. Telemetry following acute systemic PTZ reveals repeated seizures and seizure-related apnoeas, culminating in lethal apnoeas; ictal apnoeas are central - in 8 of 35 cases diaphragms initially contract tonically for 8.5 ± 15.0 s before relaxing, in the 27 remaining cases diaphragms are atonic throughout apnoeas. All terminal apnoeas are atonic. Differences in types of apnoea due to systemic PTZ in rats (mainly atonic) and mice (tonic) are likely species-specific. Certain genetic mouse models have apnoeas caused by tonic contraction, potentially due to expression of epileptogenic mutations throughout the brain, including in respiratory centres, in contrast with acquired focal epilepsies. We conclude that ictal apnoeas in the rat TeNT model result from atonic diaphragms. Relaxed diaphragms could be particularly helpful for therapeutic stimulation of the diaphragm to help restore respiration.

• Klíčová slova
• EMG, Pentylenetetrazol, SUDEP, Temporal lobe epilepsy, Tetanus toxin, hippocampus,
• MeSH
• apnoe patofyziologie   MeSH
• bránice * patofyziologie   MeSH
• chronická nemoc MeSH
• elektroencefalografie MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech * MeSH
• pentylentetrazol toxicita   MeSH
• potkani Sprague-Dawley MeSH
• relaxace svalu fyziologie   MeSH
• tetanový toxin toxicita   MeSH
• záchvaty * patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• pentylentetrazol MeSH
• tetanový toxin MeSH

Objective.The proportion of patients becoming seizure-free after epilepsy surgery has stagnated. Large multi-center stereo-electroencephalography (SEEG) datasets can allow comparing new patients to past similar cases and making clinical decisions with the knowledge of how cases were treated in the past. However, the complexity of these evaluations makes the manual search for similar patients impractical. We aim to develop an automated system that electrographically and anatomically matches seizures to those in a database. Additionally, since features that define seizure similarity are unknown, we evaluate the agreement and features among experts in classifying similarity.Approach.We utilized 320 SEEG seizures from 95 consecutive patients who underwent epilepsy surgery. Eight international experts evaluated seizure-pair similarity using a four-level similarity score. As our primary outcome, we developed and validated an automated seizure matching system by employing patient data marked by independent experts. Secondary outcomes included the inter-rater agreement (IRA) and features for classifying seizure similarity.Main results.The seizure matching system achieved a median area-under-the-curve of 0.76 (interquartile range, 0.1), indicating its feasibility. Six distinct seizure similarity features were identified and proved effective: onset region, onset pattern, propagation region, duration, extent of spread, and propagation speed. Among these features, the onset region showed the strongest correlation with expert scores (Spearman's rho = 0.75,p< 0.001). Additionally, the moderate IRA confirmed the practicality of our approach with an agreement of 73.9% (7%), and Gwet's kappa of 0.45 (0.16). Further, the interoperability of the system was validated on seizures from five centers.Significance.We demonstrated the feasibility and validity of a SEEG seizure matching system across patients, effectively mirroring the expertise of epileptologists. This novel system can identify patients with seizures similar to that of a patient being evaluated, thus optimizing the treatment plan by considering the results of treating similar patients in the past, potentially improving surgery outcome.

• Klíčová slova
• epilepsy surgery, interrater agreement, phenotyping, precision medicine, seizure matching, seizure onset zone, stereo-electroencephalography,
• MeSH
• dítě MeSH
• dospělí MeSH
• elektroencefalografie * metody   MeSH
• epilepsie * chirurgie   diagnóza   patofyziologie   MeSH
• klinické rozhodování * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• reprodukovatelnost výsledků MeSH
• stereotaktické techniky MeSH
• záchvaty diagnóza   chirurgie   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Despite extensive temporal lobe epilepsy (TLE) research, understanding the specific limbic structures' roles in seizures remains limited. This weakness can be attributed to the complex nature of TLE and the existence of various TLE subsyndromes, including non-lesional TLE. Conventional TLE models like kainate and pilocarpine hinder precise assessment of the role of individual limbic structures in TLE ictogenesis due to widespread limbic damage induced by the initial status epilepticus. In this study, we used a non-lesional TLE model characterized by the absence of initial status and cell damage to determine the spatiotemporal profile of seizure initiation and limbic structure recruitment in TLE. Epilepsy was induced by injecting a minute dose of tetanus toxin into the right dorsal hippocampus in seven animals. Following injection, animals were implanted with bipolar recording electrodes in the amygdala, dorsal hippocampus, ventral hippocampus, piriform, perirhinal, and entorhinal cortices of both hemispheres. The animals were video-EEG monitored for four weeks. In total, 140 seizures (20 seizures per animal) were analyzed. The average duration of each seizure was 53.2+/-3.9 s. Seizure could initiate in any limbic structure. Most seizures initiated in the ipsilateral (41 %) and contralateral (18 %) ventral hippocampi. These two structures displayed a significantly higher probability of seizure initiation than by chance. The involvement of limbic structures in seizure initiation varied between individual animals. Surprisingly, only 7 % of seizures initiated in the injected dorsal hippocampus. The limbic structure recruitment into the seizure activity wasn't random and displayed consistent patterns of early recruitment of hippocampi and entorhinal cortices. Although ventral hippocampus represented the primary seizure onset zone, the study demonstrated the involvement of multiple limbic structures in seizure initiation in a non-lesional TLE model. The study also revealed the dichotomy between the primary epileptogenic lesion and main seizure onset zones and points to the central role of ventral hippocampi in temporal lobe ictogenesis.

• MeSH
• elektroencefalografie MeSH
• epilepsie temporálního laloku * chemicky indukované   patofyziologie   patologie   MeSH
• hipokampus účinky léků   patologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech * MeSH
• potkani Sprague-Dawley MeSH
• tetanový toxin * toxicita   MeSH
• záchvaty * chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• tetanový toxin * MeSH

Numerous physiological processes are cyclical, but sampling these processes densely enough to perform frequency decomposition and subsequent analyses can be challenging. Mathematical approaches for decomposition and reconstruction of sparsely and irregularly sampled signals are well established but have been under-utilized in physiological applications. We developed a basis pursuit denoising with polynomial detrending (BPWP) model that recovers oscillations and trends from sparse and irregularly sampled timeseries. We validated this model on a unique dataset of long-term inter-ictal epileptiform discharge (IED) rates from human hippocampus recorded with a novel investigational device with continuous local field potential sensing. IED rates have well established circadian and multiday cycles related to sleep, wakefulness, and seizure clusters. Given sparse and irregular samples of IED rates from multi-month intracranial EEG recordings from ambulatory humans, we used BPWP to compute narrowband spectral power and polynomial trend coefficients and identify IED rate cycles in three subjects. In select cases, we propose that random and irregular sampling may be leveraged for frequency decomposition of physiological signals. Trial Registration: NCT03946618.

• MeSH
• algoritmy MeSH
• elektroencefalografie metody   MeSH
• elektrokortikografie metody   MeSH
• epilepsie * patofyziologie   diagnóza   MeSH
• hipokampus patofyziologie   fyziologie   MeSH
• lidé MeSH
• modely neurologické MeSH
• počítačové zpracování signálu MeSH
• výpočetní biologie metody   MeSH
• záchvaty patofyziologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Data comprise intracranial EEG (iEEG) brain activity represented by stereo EEG (sEEG) signals, recorded from over 100 electrode channels implanted in any one patient across various brain regions. The iEEG signals were recorded in epilepsy patients (N = 10) undergoing invasive monitoring and localization of seizures when they were performing a battery of four memory tasks lasting approx. 1 hour in total. Gaze tracking on the task computer screen with estimating the pupil size was also recorded together with behavioral performance. Each dataset comes from one patient with anatomical localization of each electrode contact. Metadata contains labels for the recording channels with behavioral events marked from all tasks, including timing of correct and incorrect vocalization of the remembered stimuli. The iEEG and the pupillometric signals are saved in BIDS data structure to facilitate efficient data sharing and analysis.

• MeSH
• elektrody MeSH
• elektrokortikografie * MeSH
• epilepsie patofyziologie   MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• oční fixace MeSH
• paměť fyziologie   MeSH
• pupila MeSH
• technologie sledování pohybu očí MeSH
• záchvaty patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• dataset MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Developing sensitive and reliable methods to distinguish normal and abnormal brain states is a key neuroscientific challenge. Topological Data Analysis, despite its relative novelty, already generated many promising applications, including in neuroscience. We conjecture its prominent tool of persistent homology may benefit from going beyond analysing structural and functional connectivity to effective connectivity graphs capturing the direct causal interactions or information flows. Therefore, we assess the potential of persistent homology to directed brain network analysis by testing its discriminatory power in two distinctive examples of disease-related brain connectivity alterations: epilepsy and schizophrenia. We estimate connectivity from functional magnetic resonance imaging and electrophysiology data, employ Persistent Homology and quantify its ability to distinguish healthy from diseased brain states by applying a support vector machine to features quantifying persistent homology structure. We show how this novel approach compares to classification using standard undirected approaches and original connectivity matrices. In the schizophrenia classification, topological data analysis generally performs close to random, while classifications from raw connectivity perform substantially better; potentially due to topographical, rather than topological, specificity of the differences. In the easier task of seizure discrimination from scalp electroencephalography data, classification based on persistent homology features generally reached comparable performance to using raw connectivity, albeit with typically smaller accuracies obtained for the directed (effective) connectivity compared to the undirected (functional) connectivity. Specific applications for topological data analysis may open when direct comparison of connectivity matrices is unsuitable - such as for intracranial electrophysiology with individual number and location of measurements. While standard homology performed overall better than directed homology, this could be due to notorious technical problems of accurate effective connectivity estimation.

• Klíčová slova
• Connectivity, Electrophysiology, Epilepsy, Persistent homology, Schizophrenia, fMRI,
• MeSH
• elektroencefalografie MeSH
• epilepsie diagnostické zobrazování   patofyziologie   MeSH
• konektom * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• modely neurologické * MeSH
• mozek diagnostické zobrazování   patofyziologie   MeSH
• nervová síť diagnostické zobrazování   patofyziologie   MeSH
• schizofrenie diagnostické zobrazování   patofyziologie   MeSH
• záchvaty diagnostické zobrazování   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The seemingly random and unpredictable nature of seizures is a major debilitating factor for people with epilepsy. An increasing body of evidence demonstrates that the epileptic brain exhibits long-term fluctuations in seizure susceptibility, and seizure emergence seems to be a consequence of processes operating over multiple temporal scales. A deeper insight into the mechanisms responsible for long-term seizure fluctuations may provide important information for understanding the complex nature of seizure genesis. In this study, we explored the long-term dynamics of seizures in the tetanus toxin model of temporal lobe epilepsy. The results demonstrate the existence of long-term fluctuations in seizure probability, where seizures form clusters in time and are then followed by seizure-free periods. Within each cluster, seizure distribution is non-Poissonian, as demonstrated by the progressively increasing inter-seizure interval (ISI), which marks the approaching cluster termination. The lengthening of ISIs is paralleled by: increasing behavioral seizure severity, the occurrence of convulsive seizures, recruitment of extra-hippocampal structures and the spread of electrographic epileptiform activity outside of the limbic system. The results suggest that repeated non-convulsive seizures obey the 'seizures-beget-seizures' principle, leading to the occurrence of convulsive seizures, which decrease the probability of a subsequent seizure and, thus, increase the following ISI. The cumulative effect of repeated convulsive seizures leads to cluster termination, followed by a long inter-cluster period. We propose that seizures themselves are an endogenous factor that contributes to long-term fluctuations in seizure susceptibility and their mutual interaction determines the future evolution of disease activity.

• Klíčová slova
• Clustering, Dynamics, EEG, Long-term profile, Probability, Seizures, Temporal lobe epilepsy, Tetanus toxin,
• MeSH
• časové faktory MeSH
• elektroencefalografie metody   trendy   MeSH
• epilepsie temporálního laloku chemicky indukované   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• tetanový toxin toxicita   MeSH
• záchvaty chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• tetanový toxin MeSH

The mechanisms underlying the emergence of seizures are one of the most important unresolved issues in epilepsy research. In this paper, we study how perturbations, exogenous or endogenous, may promote or delay seizure emergence. To this aim, due to the increasingly adopted view of epileptic dynamics in terms of slow-fast systems, we perform a theoretical analysis of the phase response of a generic relaxation oscillator. As relaxation oscillators are effectively bistable systems at the fast time scale, it is intuitive that perturbations of the non-seizing state with a suitable direction and amplitude may cause an immediate transition to seizure. By contrast, and perhaps less intuitively, smaller amplitude perturbations have been found to delay the spontaneous seizure initiation. By studying the isochrons of relaxation oscillators, we show that this is a generic phenomenon, with the size of such delay depending on the slow flow component. Therefore, depending on perturbation amplitudes, frequency and timing, a train of perturbations causes an occurrence increase, decrease or complete suppression of seizures. This dependence lends itself to analysis and mechanistic understanding through methods outlined in this paper. We illustrate this methodology by computing the isochrons, phase response curves and the response to perturbations in several epileptic models possessing different slow vector fields. While our theoretical results are applicable to any planar relaxation oscillator, in the motivating context of epilepsy they elucidate mechanisms of triggering and abating seizures, thus suggesting stimulation strategies with effects ranging from mere delaying to full suppression of seizures.

• MeSH
• biologické modely MeSH
• elektroencefalografie metody   MeSH
• lidé MeSH
• záchvaty patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The objective of this clinical practice guideline (CPG) is to provide recommendations for healthcare personnel working with patients with epilepsy on the use of wearable devices for automated seizure detection in patients with epilepsy, in outpatient, ambulatory settings. The Working Group of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) developed the CPG according to the methodology proposed by the ILAE Epilepsy Guidelines Working Group. We reviewed the published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and evaluated the evidence and formulated the recommendations following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We found high level of evidence for the accuracy of automated detection of generalized tonic-clonic seizures (GTCS) and focal-to-bilateral tonic-clonic seizures (FBTCS) and recommend the use of wearable automated seizure detection devices for selected patients when accurate detection of GTCS and FBTCS is recommended as a clinical adjunct. We also found a moderate level of evidence for seizure types without GTCS or FBTCS. However, it was uncertain whether the detected alarms resulted in meaningful clinical outcomes for the patients. We recommend using clinically validated devices for automated detection of GTCS and FBTCS, especially in unsupervised patients, where alarms can result in rapid intervention (weak/conditional recommendation). At present, we do not recommend clinical use of the currently available devices for other seizure types (weak/conditional recommendation). Further research and development are needed to improve the performance of automated seizure detection and to document their accuracy and clinical utility.

• Klíčová slova
• algorithms, automated detection, epilepsy, seizure detection, wearable devices,
• MeSH
• ambulantní monitorování přístrojové vybavení   metody   normy   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nositelná elektronika * normy   MeSH
• předškolní dítě MeSH
• senioři MeSH
• záchvaty diagnóza   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH