Seizures beget seizures is a longstanding theory that proposed that seizure activity can impact the structural and functional properties of the brain circuits in ways that contribute to epilepsy progression and the future occurrence of seizures. Originally proposed by Gowers, this theory continues to be quoted in the pathophysiology of epilepsy. We critically review the existing data and observations on the consequences of recurrent seizures on brain networks and highlight a range of factors that speak for and against the theory. The existing literature demonstrates clearly that ictal activity, especially if recurrent, induces molecular, structural, and functional changes including cell loss, connectivity reorganization, changes in neuronal behavior, and metabolic alterations. These changes have the potential to modify the seizure threshold, contribute to disease progression, and recruit wider areas of the epileptic network into epileptic activity. Repeated seizure activity may, thus, act as a pathological positive-feedback mechanism that increases seizure likelihood. On the other hand, the time course of self-limited epilepsies and the presence of seizure remission in two thirds of epilepsy cases and various chronic epilepsy models oppose the theory. Experimental work showed that seizures could induce neural changes that increase the seizure threshold and decrease the risk of a subsequent seizure. Due to the complex nature of epilepsies, it is wrong to consider only seizures as the key factor responsible for disease progression. Epilepsy worsening can be attributed to the various forms of interictal epileptiform activity or underlying disease mechanisms. Although seizure activity can negatively impact brain structure and function, the "seizures beget seizures" theory should not be used dogmatically but with extreme caution.

• Klíčová slova
• disease progression, epilepsy, epileptogenesis, kindling, seizure cluster, seizures,
• MeSH
• epilepsie * MeSH
• lidé MeSH
• mozek MeSH
• neurony MeSH
• progrese nemoci MeSH
• záchvaty * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Introduction: Perampanel is an antiepileptic drug approved in the USA and Europe as monotherapy and adjunctive therapy for focal onset seizures and as adjunctive therapy for generalized tonic-clonic seizures. Areas covered: This an overview of animal data, pharmacokinetics, and clinical data published on Perampanel indexed in PubMed. Expert opinion: Pharmacological studies suggest that perampanel acts via noncompetitive antagonism of the ionotropic AMPA receptor of glutamate. The efficacy of perampanel has been shown in animal models of epilepsy and Phase II/III clinical trials. Efficacy and safety have been evaluated in the phase III trials of adjunctive treatment of focal epilepsy with median focal onset seizure reduction rates of 23% for 4 mg/d, 26-31% for 8 mg/day, and 18-35% for 12 mg/day. Fifty percent responder rates were 29% for 4 mg/day, 33-38% for 8 mg/day, and 34-36% for 12 mg/day. A pivotal Phase III trial in generalized onset tonic-clonic seizures showed a median seizure reduction by 76.5% (8 mg) versus 38.4% placebo and 50% seizure responder rate of 64.2% versus 30.9% placebo. Perampanel showed good safety and tolerability profile across 2-12 mg doses. Perampanel as a broad-spectrum antiepileptic drug has a potential to be an alternative treatment of multiple types of epileptic seizures.

• Klíčová slova
• AMPA receptor antagonist, adjunctive therapy, anti-seizure drug, focal seizures, generalized tonic-clonic seizures, monotherapy,
• MeSH
• antikonvulziva aplikace a dávkování   farmakologie   MeSH
• epilepsie generalizovaná farmakoterapie   MeSH
• epilepsie parciální farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• nitrily MeSH
• pyridony aplikace a dávkování   farmakologie   MeSH
• záchvaty farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antikonvulziva MeSH
• nitrily MeSH
• perampanel MeSH Prohlížeč
• pyridony MeSH

The establishment of memories involves reactivation of waking neuronal activity patterns and strengthening of associated neural circuits during slow-wave sleep (SWS), a process known as "cellular consolidation" (Dudai and Morris, 2013). Reactivation of neural activity patterns during waking behaviors that occurs on a timescale of seconds to minutes is thought to constitute memory recall (O'Keefe and Nadel, 1978), whereas consolidation of memory traces may be revealed and served by correlated firing (reactivation) that appears during sleep under conditions suitable for synaptic modification (Buhry et al., 2011). Although reactivation has been observed in human neuronal recordings (Gelbard-Sagiv et al., 2008; Miller et al., 2013), reactivation during sleep has not, likely because data are difficult to obtain and the effect is subtle. Seizures, however, provide intense and synchronous, yet sparse activation (Bower et al., 2012) that could produce a stronger consolidation effect if seizures activate learning-related mechanisms similar to those activated by learned tasks. Continuous wide-bandwidth recordings from patients undergoing intracranial monitoring for drug-resistant epilepsy revealed reactivation of seizure-related neuronal activity during subsequent SWS, but not wakefulness. Those neuronal assemblies that were most strongly activated during seizures showed the largest correlation changes, suggesting that consolidation selectively strengthened neuronal circuits activated by seizures. These results suggest that seizures "hijack" physiological learning mechanisms and also suggest a novel epilepsy therapy targeting neuronal dynamics during post-seizure sleep.

• Klíčová slova
• consolidation, epilepsy, learning, memory, neural assemblies, seizures,
• MeSH
• akční potenciály fyziologie   MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• epilepsie temporálního laloku patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nervová síť patofyziologie   MeSH
• neurony fyziologie   MeSH
• paměť fyziologie   MeSH
• spánek fyziologie   MeSH
• záchvaty patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

High-frequency oscillations (HFOs) are a type of brain activity that is recorded from brain regions capable of generating seizures. Because of the close association of HFOs with epileptogenic tissue and ictogenesis, understanding their cellular and network mechanisms could provide valuable information about the organization of epileptogenic networks and how seizures emerge from the abnormal activity of these networks. In this review, we summarize the most recent advances in the field of HFOs and provide a critical evaluation of new observations within the context of already established knowledge. Recent improvements in recording technology and the introduction of optogenetics into epilepsy research have intensified experimental work on HFOs. Using advanced computer models, new cellular substrates of epileptic HFOs were identified and the role of specific neuronal subtypes in HFO genesis was determined. Traditionally, the pathogenesis of HFOs was explored mainly in patients with temporal lobe epilepsy and in animal models mimicking this condition. HFOs have also been reported to occur in other epileptic disorders and models such as neocortical epilepsy, genetically determined epilepsies, and infantile spasms, which further support the significance of HFOs in the pathophysiology of epilepsy. It is increasingly recognized that HFOs are generated by multiple mechanisms at both the cellular and network levels. Future studies on HFOs combining novel high-resolution in vivo imaging techniques and precise control of neuronal behavior using optogenetics or chemogenetics will provide evidence about the causal role of HFOs in seizures and epileptogenesis. Detailed understanding of the pathophysiology of HFOs will propel better HFO classification and increase their information yield for clinical and diagnostic purposes.

• Klíčová slova
• Computer models, Epilepsy, Epileptogenesis, Fast ripples, High-frequency oscillations, Ictogenesis, Interneurons, Ripples, Seizures,
• MeSH
• elektroencefalografie MeSH
• epilepsie patofyziologie   MeSH
• lidé MeSH
• mapování mozku * MeSH
• mozek patofyziologie   MeSH
• mozkové vlny fyziologie   MeSH
• počítačové zpracování signálu MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: The main purpose of the study was to analyze the long-term outcomes and therapeutic approaches for patients with seizures within the first year after surgery. The secondary aim of the study was to evaluate the relationship between 1-year outcome and long-term outcome and choice of therapy. METHODS: Our study was a retrospective investigation of the long-term outcomes of 95 patients (33.5% of all surgically treated patients) with seizure recurrence in the first year after surgery. The patients had follow-up visits for >5 years. RESULTS: At the 5-year follow-up visit (FU5), 28 (29.5%) of the 95 patients were completely seizure-free (International League Against Epilepsy (ILAE) class 1), 17 (17.9%) had auras only (ILAE class 2), and 21 (22.1%) were unimproved (ILAE classes 5 and 6). Statistically significant factors for these long-term outcomes were the focus localization of the epilepsy, preoperative MRI findings, and postoperative follow-up results in the first year. The patients with <3 seizure days in the first postoperative year (ILAE 3) represented 53.6% of the seizure-free patients at FU5; the patients with auras in the first year constituted 64.7% of the patients with only auras at FU5; and the patients unimproved in the first year represented 76.2% of the unimproved patients at FU5. SIGNIFICANCE: Postoperative outcome depends to a certain extent on the outcome achieved in the first postoperative year. More than one third of the patients with postoperative seizures reached a long-term seizure-free outcome, and more than half of them did not experience disabling seizures in the last outcome year. The most therapeutic options were used in patients who were minimally influenced by the operation; the majority of patients with considerable improvement because of the operation do not use any other add-on antiepileptic drugs or other kinds of therapy.

• Klíčová slova
• Add-on medication, Postoperative treatment, Reoperation, Surgery failure, Vagus nerve stimulation,
• MeSH
• časové faktory MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• pooperační komplikace diagnóza   epidemiologie   MeSH
• pooperační péče trendy   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• záchvaty diagnóza   epidemiologie   chirurgie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví 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

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.

• Klíčová slova
• consciousness, epileptic seizures, generalization, ictal rhythms, responsiveness,
• MeSH
• bezvědomí MeSH
• elektroencefalografie metody   MeSH
• epilepsie parciální * MeSH
• lidé MeSH
• mozek MeSH
• záchvaty * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Functional [psychogenic nonepileptic/dissociative] seizures (FND-seiz) and related functional neurological disorder subtypes were of immense interest to early founders of modern-day neurology and psychiatry. Unfortunately, the divide that occurred between the both specialties throughout the mid-twentieth century placed FND-seiz at the borderland between the two disciplines. In the process, a false Cartesian dualism emerged that labeled psychiatric conditions as impairments of the mind and neurological conditions as disturbances in structural neuroanatomy. Excitingly, modern-day neuropsychiatric perspectives now consider neurologic and psychiatric conditions as disorders of both brain and mind. In this article, we aim to integrate neurologic and psychiatric perspectives in the conceptual framing of FND-seiz. In doing so, we explore emerging relationships between symptoms, neuropsychological constructs, brain networks, and neuroendocrine/autonomic biomarkers of disease. Evidence suggests that the neuropsychological constructs of emotion processing, attention, interoception, and self-agency are important in the pathophysiology of FND-seiz. Furthermore, FND-seiz is a multi-network brain disorder, with evidence supporting roles for disturbances within and across the salience, limbic, attentional, multimodal integration, and sensorimotor networks. Risk factors, including the magnitude of previously experienced adverse life events, relate to individual differences in network architecture and neuroendocrine profiles. The time has come to use an integrated neuropsychiatric approach that embraces the closely intertwined relationship between physical health and mental health to conceptualize FND-seiz and related functional neurological disorder subtypes.

• Klíčová slova
• Autonomic, Biopsychosocial, Brain networks, Dissociation, Emotion, Functional seizures, Neuroendocrine, Psychogenic nonepileptic seizures,
• MeSH
• disociační poruchy psychologie   MeSH
• emoce MeSH
• konverzní poruchy * psychologie   MeSH
• lidé MeSH
• záchvaty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

218 children were admitted to paediatric clinic for acute seizures within last 5 years. Out of them, 14 children (7%) were admitted to paediatric intensive care unit (PICU) with repeated or prolonged seizures. Two children were hospitalized twice. The average age of children in time of admission was 12 months, most of the children were healthy before admission, had normal psychomotor development. The most frequent seizure manifestation was asymmetric clonic seizure. Hypoventilation and/or unconsciousness was the most frequent indication for PICU admission in addition to seizures. Febrile seizure was the most frequent diagnosis in children with shorter or less frequent episodes of seizure. Children with severe course and pharmacoresistant seizure were likely to have genetic diagnosis. The MRI scan was normal in most of the children, interictal EEG was mostly without specific finding. Midazolam was the first lime anticonvulsive medication used in most of the children, while phenobarbital, levetiracetam or phenytoin were the preferred second line drugs. Keywords: acute seizures, asymmetric clonic seizure, febrile seizure, children, paediatric intensive care unit.

• MeSH
• antikonvulziva * terapeutické užití   MeSH
• dítě MeSH
• fenobarbital terapeutické užití   MeSH
• jednotky intenzivní péče pediatrické * MeSH
• kojenec MeSH
• lidé MeSH
• midazolam terapeutické užití   MeSH
• záchvaty * diagnóza   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva * MeSH
• fenobarbital MeSH
• midazolam MeSH

OBJECTIVE: To compare persons with epilepsy (PWE) to those with psychogenic non-epileptic seizures (PNES) on measures of depression, anxiety, and alexithymia subscales (i.e., difficulty identifying emotions, difficulty describing emotions, and external-oriented thinking). MATERIAL AND METHODS: In this retrospective study, 235 epilepsy patients and 90 patients with PNES were evaluated between 2012 and 2020 at the Northeast Regional Epilepsy Group. These patients had completed the Toronto Alexithymia Scale (TAS-20), The Center for Epidemiologic Studies - Depression Scale (CES-D) and The State-Trait Anxiety Inventory (STAI). Background information was collected regarding work/student/disability status at the time of the evaluation history of psychiatric diagnosis; psychological trauma; and involvement in psychotherapy either at the time of the evaluation or prior. RESULTS: Significant differences between PWEs and those with PNES were found not only in historical data (e.g., Psychiatric History, History of Trauma, and History of Therapy) (p < .001) but also on measures of Depression (p = .002) and Anxiety (p < .001). ANOVA analysis also revealed significant differences in the distribution of the TAS-Total score, TAS-Describing emotions, and TAS-Identifying emotions. Using logistic regression (stepwise model) the optimal set of predictors for a differential diagnosis of epilepsy and PNES was combination of TAS-Identifying emotions score, history of psychological trauma, and history of therapy. The accuracy of the prediction was determined to be 80.2 %. CONCLUSIONS: Although higher alexithymia rates are present in PNES and PWEs, clinicians may find a combination of TAS-Identifying Emotion score, history of trauma, and history of psychotherapy useful in supporting a differential diagnosis. Also, a subgroup may exist among those with PNES with high levels of alexithymia, depression, and anxiety that may require a different treatment approach focused on addressing difficulties in identifying and describing their emotions and their other symptomatology.

• Klíčová slova
• Alexithymia, Anxiety, Depression, Epileptic seizures, Functional dissociative seizures, Functional neurological disorders,
• MeSH
• afekt fyziologie   MeSH
• afektivní symptomy * diagnóza   etiologie   MeSH
• deprese diagnóza   etiologie   MeSH
• dospělí MeSH
• epilepsie * psychologie   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• psychiatrické posuzovací škály MeSH
• retrospektivní studie MeSH
• úzkost * diagnóza   etiologie   MeSH
• záchvaty * psychologie   diagnóza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH