Search

Összefoglaló. Bevezetés és célkitűzés: A terápiarezisztens fokális epilepsziák sebészeti kezelése elterjedten használt kezelési lehetőség. Célunk az epilepsziasebészet-hatékonyság változásának vizsgálata egy évtizednyi távlatból a budapesti centrumban. Módszerek: Az Országos Klinikai Idegtudományi Intézetben reszektív epilepsziasebészeti beavatkozásokon átesett fokális epilepsziás betegek adatai kerültek feldolgozásra. A vizsgált 10 év beteganyagát két periódusra osztottuk a műtét időpontja szerint (2006–2010 és 2011–2016). Vizsgálati szempontjaink: demográfiai adatok, az epilepszia kezdete és típusa, mágnesesrezonancia-lelet, preoperatív rohamfrekvencia, műtéttípus és szövettani lelet. Az epileptológiai kimenetelt az Engel-klasszifikáció alapján értékeltük. Eredmények: Epilepsziasebészeti beavatkozás 187 betegen történt, akik közül 137-nél került sor reszekciós műtétre. A betegek 65%-ában temporalis, 18%-ában frontalis, míg 7%-ában olyan multilobaris epilepszia igazolódott, mely a temporalis vagy a frontalis lebenyt érintette. Teljes rohammentességet (Engel I/A) az 1. évben 68%-ban, a 2. évben 64%-ban, míg az 5. évben 63%-ban mértünk. A két intervallum összehasonlításakor az 1 éves rohammentesség aránya 60%-ról (temporalis: 67%, extratemporalis: 50%) 73%-ra (temporalis: 79%, extratemporalis: 62%) javult a második periódusban. Az etiológia szempontjából a hippocampalis sclerosis aránya 28%-ról 14%-ra csökkent, a fokális corticalis dysplasiák aránya 22%-ról 31%-ra növekedett. Következtetés: A sebészeti kezelés fokális epilepsziák esetén – alapos előzetes kivizsgálást követően – általában biztonságos és a legnagyobb arányban sikeres beavatkozás. A legkedvezőbb kimenetel temporalis lokalizációban érhető el. A hatékonyság az évek során egyre javuló tendenciát mutatott az egyre nehezebb sebészeti esetek ellenére. Ez magyarázható a sebészeti technikák fejlődésével, illetve a jobb, műtét előtti elektrofiziológiai és képalkotó technikákkal, amelyek bevezetésével pontosabb lokalizáció adható. Orv Hetil. 2021; 162(6): 219–226. Summary. Introduction and objective: The surgical treatment of medically intractable focal epilepsies is a well established practice. Our aim was to examine the efficacy of epilepsy surgery within a decade long period in our centre in Budapest. Methods: Data of drug-resistant patients with resective epilepsy surgery in the National Institute of Clinical Neurosciences were evaluated. The examined 10-year period was divided based on the year of the operation in two parts (2006–2010 and 2011–2016). The following data were collected: demography, beginning and type of epilepsy, magnetic resonance, preoperative seizure frequency, type of surgery and histology. Epileptological outcome was based on modified Engel’s classification. Results: Out of 187 surgeries, we identified 137 patients with resective intervention: 65% temporal lobe, 18% frontal, and 7% multilobar epilepsy. Seizure-freedom (Engel I/A) was 68% in the first postoperative year, 64% in the second, and 63% in the fifth year. In the first period, 1-year seizure freedom was 60% (temporal: 67% extratemporal: 50%), while in the second period it was 73% (temporal 79%, extratemporal 62%). Hippocampal sclerosis ratio dropped from 28% to 14%, while focal cortical dysplasia ratio increased from 22% to 31%. Conclusion: Surgical treatment in focal epilepsy – after thorough presurgical evaluation – is generally safe and successful. The most favorable outcome is in temporal localization. The efficacy tended to improve over time despite of the more challenging cases. This can be explained with the development of surgical techniques and improvement of presurgical localization. Orv Hetil. 2021; 162(6): 219–226.

We aim to review the impact of COVID-19 pandemic on epilepsy and epilepsy-care. While the virus has no specific link with epilepsy, it may affect the nervous system both directly and indirectly, leading to seizures in several ways. The hyper-coagulable state occurring with the infection may cause strokes leading to seizures. The infection may first manifest in the form of disturbances of consciousness and behaviour, seizures, and even status epilepticus. The interactions of antiviral/antiepileptic drugs need to be taken into account during treatment. The hypercoagulable state induced by COVID-2 infection may cause stroke, which leads to seizures. The infection can occur also as an impaired consciousness of non-epileptic origin. Interactions of antiviral/antiepileptic drugs have also to be taken into account. The pandemic itself as well as quarantines and social distancing may cause anxiety and insomnia, challenge continuous antiepileptic supply;each one carrying the risk of seizing. Young epilepsy patients with learning disabilities and mental health issues are most vulnerable, justifying their hyper-protection. The danger of infection has highlighted the role of telemedicine. Internet-based video communication may ensure full care for chro nic patients. Those methods favour bes ted patients with higher education. Epilepsy does not increase directly the risk of infection, but its comorbidities may worsen the course of the disease. Brain lesions and hypoxia, stress, insomnia and fever joining the infection increase seizure susceptibility. Because the danger of infection ma de telemedicine an essential tool of pa - tient care, education and better computer supply for those in need is crucial. © 2021 Literatura Medica Publishing House. All rights reserved.

Background When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20–65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. Methods In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. Results The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. Conclusions The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. Trial registration Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. Trial registration number: 008899/2016/OTIG. Date of registration: 08 February 2016.

We report on a peculiar way of chronic cognitive impairment associated with interictal epileptic activity during NREM sleep. We review three major groups of epilepsy: mesiotemporal epilepsy (MTLE) involving the epileptic derailment of the hippocampal declarative memory system; childhood developmental epileptic encephalopathies; and the spectrum disorders of the perisylvian communication network with the centrotemporal spike phenomenon, overarching child- and adulthood epilepsies, totaling up the majority of epilepsies in childhood. We outline high impact research-lines on the cognitive harm of epilepsy; causing specific or global cognitive decline through its interference with sleep plastic functions. We highlight the key role of interictal activity in the development of cognitive impairment and the fact that we are unarmed against this harm, antiepileptic pharmaco-therapy being ineffective against the interictal process marked by spikes and high frequency oscillations.

Obstructive sleep apnea is linked to cardiovascular disease, metabolic disorders and dementia. The precise nature of the association between respiratory events in obstructive sleep apnea, cortical or subcortical arousals, and cognitive, autonomic and oxidative stress consequences remains incompletely elucidated. Previous studies have aimed to understand the relationship between obstructive sleep apnea and arousal patterns, as defined by the cyclic alternating pattern, but results have been inconsistent, in part likely due to the presence of associated comorbidities. To better define this relationship, we analysed cyclic alternating patterns in patients with obstructive sleep apnea without any additional comorbidities. We identified 18 adult male, non-obese subjects with obstructive sleep apnea and no other comorbidities or medication history, who underwent whole-night electroencephalography and polysomnography. Cyclic alternating pattern analysis was performed and verified by certified somnologists. Pairwise linear regression analysis demonstrated an inverse relationship between obstructive sleep apnea severity and cyclic alternating pattern subtype A1, and a direct correlation with cyclic alternating pattern subtype A3. Cyclic alternating pattern subtypes A1 prevail in milder obstructive sleep apnea phenotype, whilst cyclic alternating pattern subtypes A2 and A3 overcome among moderate-to-severe obstructive sleep apnea patients. The milder obstructive sleep apnea group also presented higher sleep efficiency, and increased percentages of non-rapid eye movement stage 3 and rapid eye movement sleep, as well as longer cyclic alternating pattern sequences in N3, while severe obstructive sleep apnea patients spent more time in lighter sleep stages. These results imply/suggest a balance between cyclic alternating pattern's adaptive and maladaptive arousal processes in obstructive sleep apnea of differing severities. In milder obstructive sleep apnea (apnea-hypopnea index < 20), sleep continuity may be reinforced by cyclic alternating pattern subtype A1, whereas in more severe obstructive sleep apnea, decompensation of these sleep-stabilizing mechanisms may occur and more intrusive cyclic alternating pattern fluctuations disrupt sleep circuitry.

BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2).METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library.RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control.CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

We aimed to explore the link between NREM sleep and epilepsy. Based on human and experimental data we propose that a sleep-related epileptic transformation of normal neurological networks underlies epileptogenesis. Major childhood epilepsies as medial temporal lobe epilepsy (MTLE), absence epilepsy (AE) and human perisylvian network (PN) epilepsies - made us good models to study. These conditions come from an epileptic transformation of the affected functional systems. This approach allows a system-based taxonomy instead of the outworn generalized-focal classification. MTLE links to the memory-system, where epileptic transformation results in a switch of normal sharp wave-ripples to epileptic spikes and pathological high frequency oscillations, compromising sleep-related memory consolidation. Absence epilepsy (AE) and juvenile myoclonic epilepsy (JME) belong to the corticothalamic system. The burst-firing mode of NREM sleep normally producing sleep-spindles turns to an epileptic working mode ejecting bilateral synchronous spike-waves. There seems to be a progressive transition from AE to JME. Shared absences and similar bilateral synchronous discharges show the belonging of the two conditions, while the continuous age windows - AE affecting schoolchildren, JME the adolescents - and the increased excitability in JME compared to AE supports the notion of progression. In perisylvian network epilepsies - idiopathic focal childhood epilepsies and electrical status epilepticus in sleep including Landau-Kleffner syndrome - centrotemporal spikes turn epileptic, with the potential to cause cognitive impairment. Postinjury epilepsies modeled by the isolated cortex model highlight the shared way of epileptogenesis suggesting the derailment of NREM sleep-related homeostatic plasticity as a common step. NREM sleep provides templates for plasticity derailing to epileptic variants under proper conditions. This sleep-origin explains epileptiform discharges' link and similarity with NREM sleep slow oscillations, spindles and ripples. Normal synaptic plasticity erroneously overgrowing homeostatic processes may derail toward an epileptic working-mode manifesting the involved system's features. The impact of NREM sleep is unclear in epileptogenesis occurring in adolescence and adulthood, when plasticity is lower. The epileptic process interferes with homeostatic synaptic plasticity and may cause cognitive impairment. Its type and degree depends on the affected network's function. We hypothesize a vicious circle between sleep end epilepsy. The epileptic derailment of normal plasticity interferes with sleep cognitive functions. Sleep and epilepsy interconnect by the pathology of plasticity.

The aim of this review is to summarize and discuss the strong bond between NREM sleep and epilepsy underlain by the shared link and effect on brain plasticity. Beyond the seizure occurrence rate, sleep relatedness may manifest in the enhancement of interictal epileptic discharges (spikes and pathological ripples). The number of the discharges as well as their propagation increase during NREM sleep, unmasking the epileptic network that is hidden during wakefulness. The interictal epileptic discharges associate with different sleep constituents (sleep slow waves, spindling and high frequency oscillations); known to play essential role in memory and learning. We highlight three major groups of epilepsies, in which sleep-related plastic functions suffer an epileptic derailment. In absence epilepsy mainly involving the thalamo-cortical system, sleep spindles transform to generalized spike-wave activity. In mesio-temporal epilepsy affecting the hippocampal declarative memory system, the sharp wave ripples derail to dysfunctional epileptic oscillations (spikes and pathological ripples). Idiopathic childhood epilepsies affecting the perisylvian network may progress to catastrophic status electricus during NREM sleep. In these major epilepsies, NREM sleep has a pivotal role in the development and course of the disorder. Epilepsy is born in-, and exhibits its pathological properties during NREM sleep. Interictal discharges are important causative agents in this process.

Aims - Overview of the new data about the strong link of sleep and epilepsy and conjoining cognitive impairment. Methods - Search for relevant references and summary of our own research activity on the topic. Results - Strong interrealtionship exists between epilepsy and plastic brain functions (memory processing and synaptic homeostasis) and the working modes of NREM sleep. In the most frequent childhood and adult epilepsy networks responsible for plastic functions can be derailed to an epileptic level of excitability, and suffer a transitory or permanent epileptic transformation. Exampling on the three big epilepsies: absence epilepsy; medial temporal lobe epilepsy; and childhood idiopathic focal age dependent epilepsy spectrum we demonstrate the most important features of this epileptic transformation. The association of cognitive impairment to certain sleep dependent epilepsies gains explanation by the epilepsy caused interference with slow wave decline (ICFE) and memory consolidation (MTLE) during NREM sleep. This paper serves also to introduce the concept of sleep dependent system epilepsies. Conclusions - We provide evidences about shared mechanisms among sleep related epilepsies being the derailment of sleep plastic funcions toward exaggerated excitability determined by the inherent possibilities of the signal transduction properties.

Slow waves recorded with EEG in NREM sleep are indicative of the strength and spatial extent of synchronized firing in neuronal assemblies of the cerebral cortex. Slow waves often appear in the A1 part of the cyclic alternating patterns (CAP), which correlate with a number of behavioral and biological parameters, but their physiological significance is not adequately known. We automatically detected slow waves from the scalp recordings of 37 healthy patients, visually identified CAP A1 events and compared slow waves during CAP A1 with those during NCAP. For each slow wave, we computed the amplitude, slopes, frequency, synchronization (synchronization likelihood) between specific cortical areas, as well as the location of origin and scalp propagation of individual waves. CAP A1 slow waves were characterized by greater spatial extent and amplitude, steeper slopes and greater cortical synchronization, but a similar prominence in frontal areas and similar propagation patterns to other areas on the scalp. Our results indicate that CAP A1 represents a period of highly synchronous neuronal firing over large areas of the cortical mantle. This feature may contribute to the role CAP A1 plays in both normal synaptic homeostasis and in the generation of epileptiform phenomena in epileptic patients.

Frontotemporal dementia (FTD) is a frequent cause of cognitive decline. While epilepsy is an important comorbidity of Alzheimer's disease, we lack studies on its presence in FTD. We report on an FTD patient with transient, short-term changes of behavior and cognitive performance suggesting non-convulsive epilepsy. Video-EEG recording with foramen ovale (FO) electrodes revealed mesio-temporal epileptiform potentials, undetectable by scalp leads. We also found beta spindles in the FO electrodes, not described in the literature. We conclude that video-EEG monitoring with FO electrodes might usefully complement the assessment of dementia-associated epilepsy opening new perspectives in dementia-research.

Accumulating evidence suggests that epileptic seizures originating from the temporal lobe (TL) occur in cats. Typically, affected animals have clinically focal seizures with orofacial automatisms including salivation, facial twitching, lip smacking, chewing, licking, and swallowing. Motor arrest and autonomic and behavioral signs also may occur. Many affected cats have magnetic resonance imaging (MRI) changes within the hippocampus or histopathologically confirmed hippocampal sclerosis or necrosis. From the 1950s to the 1980s, cats frequently were used as animal models for neurophysiological experiments and electrophysiological studies, from which important basic knowledge about epilepsy originated, but which has been rarely cited in clinical veterinary studies. These studies were reviewed. Experimental research on cats showed the widespread anatomical connections among TL structures. The ictal clinical signs originating from the hippocampus, amygdala, or lateral temporal cortex are similar, because of their dense interconnections. The ictal signs can be divided into autonomic, somatic, and behavioral. For research purposes, a 6-stage system was established, reflecting the usual sequential progression from focal to generalized seizure: attention response (1), arrest (2), salivation, licking (3), facial twitching (4), head turning or nodding (5), and generalized clonic convulsions (6). Knowledge of this data may help in recognizing low-stage (stage 1 or stage 2) epileptic seizures in clinical practice. Early experimental research data are in accordance with recent clinical observations regarding ictal clinical signs of TL epileptic seizures in cats. Furthermore, the research data supports the idea that TL epilepsy represents a unique clinical entity with a specific seizure type and origin in cats.

SummaryIntroduction.Medial temporal lobe epilepsy (MTLE) is the most frequent form of epilepsy in adulthood. It is classified as local/regional epilepsy. However, there is increasing evidence of the involvement of both temporal lobes and this provides abundant arguments to question this view, and consider MTLE as one of the typical bilateral system epilepsies.Aim.To provide a contemporary review of medial temporal lobe epilepsy, discussing the bilateral aspects, with reference to epilepsy surgery.Methods.A literature review and a resume of the author’s own experiences with MTLE patients.Results.Recent electrophysiological and neuroimaging data provide convincing data supporting that MTLE is a bilateral disease. The uni-and bilateral features form a continuum and the participation rate of the two temporal lobes determine course and surgical perspective of the individual patient.Conclusions.The contradictory data of invasive presurgical evaluations of MTLE patients suggest that there need to identify further indicatory markers of bilaterality and thus change the presurgical evaluation from the non-invasive towards the invasive ways. The mechanisms of the interrelationship between the two temporal lobes in MTLE warrants further research.

We aimed to integrate new data about K-complex (KC) physiology and relate KC to other low-frequency waves observed in slow wave sleep. KC can be considered a 'prototype' of reactive sleep slow waves. Similarly to slow waves, KCs feature up- and down-states, they are subject to homeostatic regulation but they are also associated with sensory activation. As a part of the continuum of reactive sleep slow waves, the study of the KC may offer a better understanding of how slow waves are activated by the sensory system. KCs appear to have a special place among sleep slow waves and in the newly established framework of input-related NREM sleep regulation. It is a key element highlighting how the brain may choose to maintain sleep in response to a sensory input when facing the question "to wake or not to wake".

Aim We aim to study the mechanism of reflex seizure triggering in close link with the system-epilepsy concept. Method We use data and theories presented in the literature and scrutinize a few illustrative cases. Conclusions The prerequisite of seizure triggering is an epilepsy-prone brain network. When it is activated, it may produce seizures manifesting the function(s) of the same system. Beyond classical reflex seizures triggered by sensory-motor stimuli, we extend the reflex-epilepsy concept to seizures induced by the normal activation of epilepsy-prone systems e.g. praxis-induced seizures and those of sleep/wake system epilepsies elicited by falling asleep (absences) or arousals from NREM sleep (seizures of genetic frontal lobe epilepsy). We suggest that normal functioning of epilepsy-prone systems may trigger seizures in epilepsies in general.

We overview here the new data about the epileptic spectrum disorders within the frame of perisylvian epileptic network since our first trial to synthetize knowledge about this system epilepsy (Halasz et al., 2005). We found evidences for a continual features relating together syndromes constituting this spectrum disorder in several fields: in sharing genetic origin, in common perisylvian human communication circuitry, in NREM sleep related potentiation of interictal epileptiform discharges of the centro-temporal spike phenomenon and in the discharge related cognitive impairment, reflecting functional deficits in human communication abilities. The transformation of a part of the children to develop into a malignant course with different degree of residual cognitive loss, through compromising sleep plastic functions, by the epileptic discharges during sleep, beside pure genetic origin, is still under research. Both factual data and new conceptual approaches helps understand better the developmental childhood epilepsies.

SUMMARY Introduction. The seizure propagation phenomenon by inducing remote symptoms brings several difficulties in finding the seizure onset and delineating the epileptic network which should be taken into consideration in epilepsy surgery. By demonstrating a difficult (MRI negative) epilepsy surgery case explored with invasive presurgical evaluation we highlight the importance to recognise the secondary sensory area and to explore the the parieto-opercular-insular-medial frontal network in certain cases. A further conclusion is the consideration of the redistributory role of the insula as a special structure in the cerebral connectome, having a role in epileptic network organisation. Aims. To support the role of the insula in the organisation of an opercular – medial frontal epileptic network and to confirm Penfield’s the “second somatic sensory leg area” by way of a case report. We try to give an up to date exploration of our patient’s remote epileptic seizures by way of a connectome. Methods. The epileptic disorder was studied with intensive video EEG monitoring and two times 3T MRI. Interictal FDG (fluorodeoxyglucose) PET was also undertaken. Beside the scalp EEG and computerized frequency analysis, the evaluation was performed by invasive EEG with 2 grids and 2 strips and an insular deep electrode in addition. Electrical cortical stimulation and cortical mapping were also undertaken. Results. The video-EEG study revealed the complex seizure semiology. The left sided global somatosesensory aura in the leg, followed supplementary motor area manifestations represented a remote seizure. The seizure onset zone and the symptomatogenic zone were localised by the invasive electrophysiology. With the insular deep electrode we succeeded to explore the propagation of ictal activity to the insula and later to frontal medial surface. The PET, the negative 3T MRI results and the postprocessing morphometry confirmed the lesional origin and localised the epileptogenic area to the second somato-sensory field where a dysgenesis was located. Conclusions. By preoperative invasive video-EEG evaluation, the second somato-sensory leg area was delineated as the seizure onset zone. The resection of this area by IIb type cortical dysgenesis, resulted in a complete relief of the seizures. The invasive video-EEG revealed the peculiar role of the insula in the propagation of the epileptic seizure from the second sensory leg area to the ipsilateral fronto-medial supplemetary motor area. Our results, confirm, that the insula has a relay or node function on the parietal opercular-fronto-medial epileptic network. The connectome of the insula is a further additive of the scale-free features of the remote epileptic networks.

Absence epilepsy (AE) and nocturnal frontal lobe epilepsy (NFLE) are system epilepsies of the sleep–wake system.

Childhood idiopathic regional (polyfocal) hyperexcitability conditions (HIECs) are held to be developmental abnormalities of genetic origin without gross structural lesions. The exact genetic background has remained unclear. These conditions start in early childhood—with some age variance—when the brain is in a plastic state. Intensive spiking during non–rapid eye movement (NREM) sleep is a typical feature. Some of the patients undergo a further increase and exaggeration of spiking during night sleep, progressing to an electrical status epilepticus leading to a serious cognitive decline. The NREM sleep activation of inrerictal epileptiform discharges (IEDs) in HIEC patients is a well-known feature. The continuous transformation of IEDs to electrical status epilepticus in sleep (ESES) occurs with variable activation, localization, synchronization, and amount, but with no basic change in the original (before ESES) IED discharge morphology. Therefore, ESES and Landau–Kleffner syndrome (LKS) are clear examples of cognitive decline caused by sleep IED activation (diffuse in ESES and regional in LKS), similar to medial temporal lobe epilepsy, in which sleep spiking interferes with memory consolidation. Although the cognitive consequences reflect an important quality change in the outcome of these children, the interictal discharges do not change, just their activation during NREM sleep.

Medial temporal lobe epilepsy (MTLE) is the epilepsy of the hippocampo–frontal memory system. Slow-wave sleep has an important role in its organization with sleep slow oscillation. The most important consequence of the hippocampal participation in MTLE is interictal spiking penetrating into the physiological hippocampo–frontal memory consolidation system, interfering with memory consolidation during slow-wave sleep. It is likely that there are more MTLE symptoms linked to memory disturbances than we had expected. Contemporary research has evidenced that MTLE is a bilateral disease. In addition to the possibility of a genuine bilateral temporal involvement, several arguments support the possibility of a progressive scenario in which unilateral temporal lobe epilepsy may involve the contralateral lobe, resulting in a dynamic bilateral interrelationship. In MTLE, there is a continuum between uni- and bilateral participation of the temporal lobes. Interictal and subclinical activity and the dynamic relationship of both temporal lobes need to be taken into account when planning surgery. We need therapeutic strategies for targeting the interictal events (not just the seizures) and for improving the disorder of sleep plastic functions in MTLE.

The Ach receptor gene mutations render the cholinergic ascending arousal system over-sensitive to arousals during NREM sleep; resulting in arousal-linked seizure fragments and full-blown seizures with behavioural manifestations from plain arousal behaviours to alarm reactions with hypermotor features. The semiology and the occurrence-pattern of seizures can be explained by an increased propensity to arousal and a dissociation between the partially activated brain and a sleeping (dysfunctional) dorso-frontal cortical system. The clinical semiology of the genetic variations and sporadic cases do not differ.

Epilepsies, especially mesiotemporal epilepsy in adulthood, are frequently associated with chronic cognitive loss, psychiatry symptoms and conditions. We aim to present the pathophysiology of interictal psychiatric comorbidities interlocked with cognitive loss; severely compromising the quality of life of epilepsy patients. We will present the mechanism of cognitive harm related to interictal spiking; and the abnormalities of brain networks in epilepsy, especially of the default mode network, briefly looking into psychosocial and pharmacology effects, too. In addition to seizures, interictal epileptic activity, mainly in sleep, may exert chronic cognitive harm, increasing the risk for primarily non-cognitive psychotic conditions as well. Interictal spikes and pathological high frequency oscillations curiously resemble normal memory traces; enabling them to “behave” and be mistaken for engrams by the memory process. Epileptic activity impairs the white and grey matter of the brain; likely contributing to brain network changes. The epileptic network changes resemble those seen in non-epileptic psychiatry conditions, offering a network-interpretation of psychiatric comorbidity.

Juvenile idiopathic myoclonic epilepsy (JME) starts in adolescence and young adulthood. Antiepileptic drugs, especially valproic acid, result in permanent freedom from seizures; however, reducing and stopping medication may lead to the recurrence of seizures. The typical seizure types are myocloni with no disturbance of consciousness, generalized tonic–clonic, and absence seizures. Reflex seizures—induced by a consistent triggering stimulus—occur in 50% of patients, and a reflex mechanism probably underlies many “spontaneous” seizures. There are four types of reflex epileptic features: (1) genetic photosensitivity ( Wolf and Goosses, 1986 ) in the form of “photoparoxysmal response,” affecting up to 90% of JME patients (Appleton et al., 2000); (2) sensitivity to eye closure ( fixation off activity ), 15%–20% of patients; (3) orofacial reflex myocloni , presenting as rapid small jerks in the perioral muscles, activated by language-related activities; and (4) praxis - related reflex epilepsy (Matsuoka et al., 2000; Yacubian et al., 2014). Similar to absence epilepsy, a dysfunction of the corticothalamic system underlies JME, but clinical and neuroimaging data suggest the participation of motor and cognitive networks in JME. In the section “Reading Epilepsy,” we include a related (spectrum) condition, featured by orofacial reflex myocloni (Yacubian et al., 2015), affecting 25%–30% of JME patients (Salek-Haddadi et al., 2009). The genetically determined hyperexcitability of the speech network underlies reading epilepsy; reading or any verbal activity may trigger a seizure. Idiopathic generalized epilepsy is not a tenable construction any more, and the multilevel incongruence regarding the EEG, seizure semiology, and genotypic features of JME obstructs its clear classification.

Epileptiform activity in various but not all epilepsy and recording types and cerebral areas is more frequent in NREM sleep, and especially during sleep periods with high-amplitude EEG slow waves. Slow waves synchronize high-frequency oscillations: physiological activity from the theta through the gamma band usually appears during scalp-positive upstates while epileptiform activity occurs at transitory phases and the scalp-negative downstate. It has been proposed that interictal discharges (IIDs) are facilitated by the high degree of neuronal firing synchrony during slow wave transitory and downstates. This would suggest that their occurrence increases as a function of slow wave synchronization, indicated by greater amplitude, steeper slopes and higher EEG signal synchronization. We investigated the occurrence of IIDs during NREM sleep slow waves in epileptic patients undergoing presurgical electrophysiological monitoring. Intracranially registered IIDs preferentially occurred during the scalp-negative downstates of frontal scalp slow waves in all subjects. IID occurrence was more frequent during larger slow waves in the pooled sample and a subset of subjects. However, slow wave slope steepness and EEG signal synchronization between two frontal scalp channels was not significantly associated with IID occurrence. Our results indicate that IIDs indeed do not occur at the same slow wave phase as physiological rhythms, but contrary to previous hypotheses their occurrence is not strongly affected by EEG synchronization.

Non-rapid eye movement (NREM) sleep is characterized by recurring transient events (Cyclic Alternating Patterns, CAP), some of which consist of increased slow wave activity (A1 subtype). Such transient slow-wave events may play an important role in NREM sleep regulation and are known to facilitate epileptiform activity. In our study we investigated the relationship between interictal spike activity and Cyclic Alternating Patterns in three epileptic patients, using simultaneous scalp electroencephalogram (EEG) recording and intracranial electrocorticography. A significant increase of interictal activity was found during CAP A1 subtypes. A positive correlation between scalp EEG delta power and spike activity was found only in CAP A1 subtypes, but not during other events. These results show that transient (but not subcontinuous) delta activity has a facilitating effect on epileptoform activity, also suggesting a functional dissociation between morphologically similar delta activities.

The veterinary literature on epilepsy in cats is less extensive than that for dogs. The present review summarizes the most important human definitions related to epilepsy and discusses the difficulties in applying them in daily veterinary practice. Epileptic seizures can have a wide range of clinical signs and are not necessarily typical in all cases. Whether a seizure event is epileptic can only be suspected based on clinical, laboratory, and neuroimaging findings as electroencephalography diagnostic techniques have not yet been developed to a sufficiently accurate level in veterinary medicine. In addition, the present review aims to describe other diagnoses and nonepileptic conditions that might be mistaken for epileptic seizures. Seizures associated with hippocampal lesions are described and discussed extensively, as they seem to be a special entity only recognized in the past few years. Furthermore, we focus on clinical work‐up and on treatment that can be recommended based on the literature and summarize the limited data available relating to the outcome. Critical commentary is provided as most studies are based on very weak evidence.

The article summarises the role of input and consequent phasic events in the dynamism of non-rapid eye movement (NREM) sleep and in homeostatic slow-wave economy during sleep. Then, an overview of the mechanism of how micro-arousals in NREM sleep gate epileptic events in absence epilepsy (AE) and in sporadic and autosomal dominant nocturnal frontal lobe epilepsy (NFLE/ADNFLE) is presented. The ictal type of generalised spike-wave discharges (SWDs) are associated with a special vigilance level in between NREM, rapid-eye movement (REM) and wake state. This transitional state is characterised by input-driven bidirectional fluctuations. Among them, SWDs are linked to A1 type A phases of CAP and therefore seem to be associated with shifts towards NREM sleep (sleep induction). In ADNFLE (and presumably in NFLE), micro-arousals release epileptic events in NREM sleep probably due to epileptic sensitisation of the cholinergic arousal system by the known acetylcholine (ACh) receptor mutations affecting the arousal system, giving rise to the epileptic (and also parasomniac) episodes. In both kinds of these system epilepsies (AE and NFLE), epileptic events can be released by phasic events during NREM sleep. The difference is that absences are activated in reactive states with a sleep-promoting, antiarousal effect, while in NFLE the epileptic disorder is interwoven with the cholinergic arousal function. The role of arousal/antiarousal in NFLE and AE fits nicely with the hypothesis that these epilepsies are disorders of two antagonistic thalamo-frontal systems involved in functions NREM sleep and wakefulness.

Background. The relationship between sleep and epilepsy has been long ago studied, and several excellent reviews are available. However, recent development in sleep research, the network concept in epilepsy, and the recognition of high frequency oscillations in epilepsy and more new results may put this matter in a new light. Aim. The review address the multifold interrelationships between sleep and epilepsy networks and with networks of cognitive functions. Material and Methods. The work is a conceptual update of the available clinical data and relevant studies. Results and Conclusions. Studies exploring dynamic microstructure of sleep have found important gating mechanisms for epileptic activation. As a general rule interictal epileptic manifestations seem to be linked to the slow oscillations of sleep and especially to the reactive delta bouts characterized by A1 subtype in the CAP system. Important link between epilepsy and sleep is the interference of epileptiform discharges with the plastic functions in NREM sleep. This is the main reason of cognitive impairment in different forms of early epileptic encephalopathies affecting the brain in a special developmental window. The impairment of cognitive functions via sleep is present especially in epileptic networks involving the thalamocortical system and the hippocampocortical memory encoding system.

A wide variety of etiologies may cause different kinds of epileptic seizures in cats. The etiological grouping follows the human classification. Structural epilepsy, idiopathic epilepsy, epilepsy of unknown cause, and reactive epileptic seizures can be classified. Semiological classification is not established in feline medicine, however a subgroup of epileptic cats was recognized in the past decade. The evidence of spontaneous temporal lobe epilepsy in the cat is a relatively new finding in feline epilepsy research and clinical practice. Spontaneously occurring epileptic seizures associated with neuronal necrosis in the hippocampus and piriform lobe, in pet cats, were first described in Switzerland more than 15 years ago, and since then reported many times in different countries. Such cats clinically show complex partial seizures (CPS) with orofacial automatism: salivation, facial twitching, lip smacking, chewing, licking, and swallowing. Likewise, arrest, vegetative, and behavioral signs also occur. MRI data suggest bilateral hippocampal T1 hypointensity and T2 and FLAIR hyperintensity, in some cases. Histopathological findings include varying degrees of neuronal necrosis or sclerosis in the hippocampus. A recent study supports that limbic encephalitis associated with autoantibodies against the voltage-gated potassium channel (VGKC)-complex can be the etiology in some cases. Leucine-rich glioma-inactivated 1 (LGI1) was detected as target of the immune reaction in VGKC antibody positive cats. It should be considered that the cat may serve as an animal model for certain aspects of temporal lobe epilepsy in human medicine.

© 2015, Springer-Verlag Berlin Heidelberg. Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAAreceptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both—behaving differently during ictal and interictal states in a context-dependent manner—remains to be established.

A 5-year-old, female client-owned cat presented with acute onset of focal epileptic seizures with orofacial twitching and behavioural changes. Magnetic resonance imaging showed bilateral temporal lobe hyperintensities and the EEG was consistent with ictal epileptic seizure activity. After antiepileptic and additional corticosteroid treatment, the cat recovered and by 10 months of follow-up was seizure-free without any problem. Retrospectively, antibodies to LGI1, a component of the voltage-gated potassium channel-complex, were identified. Feline focal seizures with orofacial involvement have been increasingly recognised in client-owned cats, and autoimmune limbic encephalitis was recently suggested as a possible aetiology. This is the first report of EEG, MRI and long-term follow-up of this condition in cats which is similar to human limbic encephalitis.

Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammation, and high serum titers of Abs against proteins of the VGKC-complex, particularly leucine-rich, glioma-inactivated 1 (LGI1). Most patients are diagnosed promptly and recover substantially with immunotherapies; consequently, neuropathological data are limited. We have recently shown that feline complex partial cluster seizures with orofacial involvement (FEPSO) in cats can also be associated with Abs against VGKC-complexes/LGI1. Here we examined the brains of cats with FEPSO and compared the neuropathological findings with those in a human with VGKC-complex-Ab limbic encephalitis. Similar to humans, cats with VGKC-complex-Ab and FEPSO have hippocampal lesions with only moderate T-cell infiltrates but with marked IgG infiltration and complement C9neo deposition on hippocampal neurons, associated with neuronal loss. These findings provide further evidence that FEPSO is a feline form of VGKC-complex-Ab limbic encephalitis and provide a model for increasing understanding of the human disease.

OBJECTIVES A retrospective study has been done at the Bethesda Children's Hospital Epilepsy Center with those patients whose EEG records fulfilled in one or more records the criteria of electrical status epilepticus in slow wave sleep (ESES) pattern, occupying at least 75% of NREM sleep with bilateral discharges, and had detailed disease history and long term follow-up data, between 2000 and 2012. PATIENTS AND METHODS--Thirty-three patients (mean 11.1 +/- 4.2 years of age) were studied by 171 sleep EEG records. Sleep was recorded after sleep deprivation or during spontaneous sleep at least for one hour length of NREM. From the 492 EEGs, 171 sleep records were performed (average five/patient). Average follow-up time was 7.5 years. Eighty-two ESES records have been analyzed in 15 non-lesional and 18 lesional (11 with dysgenetic and seven with perinatal-asphyxic or vascular origin) patients. Variability of seizure types, seizure frequency and frequency of status epilepticus was higher in the lesional group. Impairment of the cognitive functions was moderate and partial in the non-lesional, while severely damaged in the lesional group. RESULTS EEG records of 29 patients shawed unihemispherial spike fields with a perpendicular axis (in anterior, medial and posterior variants) to the Sylvian fissure, regardless their lesional or non-lesional origin. Only three (lone nonlesional and two lesional) patients had bilateral synchronous spike-wave discharges with bilateral symmetric frontocentral spike fields. The individual discharges of the sleep EEG pattern were very similar to the awake interictal records except their extension in time and field, their increased number, amplitude, and continuity of them and furthermore in the increased trans-hemispheral propagation and their synchronity. CONCLUSIONS Assumed circuits involved in the pathomechanism of discharges during NREM sleep in ESES are discussed based on our findings.

We report an evaluation of the treatment and outcome of cats with suspected primary epilepsy. Phenobarbital therapy was used alone or in combination with other anti-epileptic drugs. Outcome after treatment was evaluated mainly on the basis of number of seizures per year and categorised into four groups: seizure-free, good control (1–5 seizures per year), moderate control (6–10 seizures per year) and poor control (more than 10 seizures per year). About 40–50% of cases became seizure-free, 20–30% were considered good-to-moderately controlled and about 30% were poorly controlled depending on the year of treatment considered. The duration of seizure events after treatment decreased in 26/36 cats and was unchanged in eight cats. The subjective severity of seizure also decreased in 25 cats and was unchanged in nine cats. Twenty-six cats had a good quality of life, nine cats an impaired quality of life and one cat a bad quality of life. Despite being free of seizures for years, cessation of treatment may lead to recurrence of seizures in most cats.

Summary Purpose: To evaluate the efficacy and safety profile of eslicarbazepine acetate (ESL) added to stable antiepileptic therapy in adults with partial-onset seizures. Methods: Data from 1,049 patients enrolled from 125 centers, in 23 countries, in three phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2-week titration period, ESL was administered at 400 mg, 800 mg, and 1,200 mg once-daily doses for 12 weeks. Key Findings: Seizure frequency was significantly reduced with ESL 800 mg (p 10% patients) were dizziness, somnolence, and headache. The incidence of AEs in ESL groups compared to placebo was generally consistent among different subpopulations. Significance: Once-daily ESL 800 mg and 1,200 mg showed consistent results across all efficacy and safety end points. Results were independent of study population characteristics and type and number of concomitant AEDs.

Summary Purpose: To evaluate the long-term efficacy and safety of once daily eslicarbazepine acetate (ESL) as adjunctive therapy for partial-onset seizures in adults with epilepsy. Methods: One-year open-label treatment extension with ESL in patients who completed a placebo-controlled pivotal study (Epilepsia 2009; 50: 454–463). Starting dose was 800 mg once daily, for 4 weeks; thereafter, dose could be titrated up or down. Doses of concomitant antiepileptic drugs were to be kept stable. Results: Overall, 314 patients were enrolled. The intent-to-treat population consisted of 312 patients, and 239 (76.6%) completed 1 year of treatment. ESL median dose was 800 mg once daily. Compared to baseline, median seizure frequency decreased by 39% during the first 4 weeks and between 48% and 56% thereafter. The responder rate (≥50% seizure reduction) was 41% during weeks 1–4 and, thereafter ranged between 48% and 53%. The proportion of seizure-free patients per 12-week interval ranged between 8.7% and 12.5%. Quality of life, as measured by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), and depressive symptoms, as measured by the Montgomery Asberg Depression Rating Scale (MADRS), improved significantly compared to baseline. Treatment-emergent adverse events (TEAEs) were reported by 51% of patients. The most frequent TEAEs were headache (10%), dizziness (10%), diplopia (5%), and nasopharyngitis (5%). TEAEs were mostly (97%) of mild to moderate intensity. Eleven patients (3.5%) discontinued due to TEAEs. There were no results of laboratory tests raising safety concerns. Discussion: Sustained therapeutic effect, favorable tolerability and safety, and an improvement in quality of life and depressive symptoms were observed during long-term add-on treatment of partial-onset seizures in adults with once daily ESL.

The endocannabinoid system plays a central role in retrograde synaptic communication, and controls both glutamatergic and GABAergic transmission via type 1 cannabinoid receptors (CB1). Both in sclerotic human hippocampi and in the chronic phase of pilocarpine-induced epilepsy in mice with sclerosis, CB1 receptor-positive interneuron somata were preserved both in the dentate gyrus and in the CA1 area, and the density of CB1 immunostained fibers increased considerably in the dentate molecular layer. This suggests that, while CB1 receptors are known to be reduced in density on glutamatergic axons, the CB1 receptor-expressing GABAergic axons sprout, or there is an increase of CB1 receptor levels on these fibers. The changes of CB1 immunostaining in association with the GABAergic inhibitory system appears to correlate with the severity of pyramidal cell loss in the CA1 subfield. These results confirm the involvement of the endocannabinoid system associated with GABAergic transmission in human TLE, as well as in the chronic phase of the pilocarpine model in mice. Pharmacotherapy aimed at the modulation of endocannabinoid-mediated retrograde synaptic signaling should take into account the opposite change in CB1 receptor expression observed on glutamatergic versus GABAergic axon terminals.

Vagus nerve stimulation (VNS) is a nonpharmacologic therapeutic option for patients with intractable epilepsy. Better clinical outcomes were recorded in nonfocal and Lennox-Gastaut syndrome (LGS). We conducted a 2-year, open label, prospective study to measure the seizure outcome of 26 VNS patients. The seizure numbers were assessed using clinician's global impression scale (CGI) and patient diaries. The average seizure reduction was 23% at the first year and 22% at the second year. Seizure reduction was more pronounced among patients with nonfocal than with focal epilepsy. The response rate was 50% at first year and 30% at the second year. The best CGI record for clinically significant improvement was 15% in the LGS group. The only statistically significant result was the reduction of the generalized tonic-clonic seizures (GTCS). The side-effect profile was good; however, the large number of mild and reversible effects influenced the stimulation parameters and thus probably the effectiveness of the therapy. We suggest that VNS is an optional treatment mostly in cases of therapy-resistant Lennox-Gastaut syndrome. Patients with GTCS may experience improvement such as reduction of seizure severity. We conclude that VNS is a safe neuromodulatory treatment, but future developments of neuromodulatory approaches are needed.

Calretinin is expressed mainly in interneurons that specialize to innervate either principal cell dendrites or other interneurons in the human hippocampus. Calretinin-containing cells were shown to be vulnerable in animal models of ischaemia and epilepsy. In the human hippocampus, controversial data were published regarding their sensitivity in epilepsy. Therefore we aimed to reveal the fate of this cell type in human epileptic hippocampi. Surgically removed hippocampi of patients with drug-resistant temporal lobe epileptic (n = 44) were examined and compared to control (n = 8) samples with different post-mortem delays. The samples were immunostained for calretinin and the changes in the distribution, density and synaptic target selectivity of calretinin-positive cells were analysed. Control samples with post-mortem delays longer than 8 h resulted in a reduced number of immunolabelled cells compared to controls with short post-mortem delay. The number of calretinin-positive cells in the epileptic tissue was considerably decreased in correlation with the severity of principal cell loss. Preserved cells had segmented and shortened dendrites. Electron microscopic examination revealed that in controls, 23% of the calretinin-positive interneuronal terminals targeted calretinin-positive dendrites, whereas in the epileptic samples it was reduced to 3-5%. The number of contacts between calretinin-positive dendrites also dropped. The present quantitative data suggest that calretinin-containing cells in the human hippocampus are highly vulnerable, thus inhibition mediated by dendritic inhibitory cells and their synchronization by interneuron-specific interneurons may be impaired in epilepsy. We hypothesize that reorganization of the interneuron-selective cells may be implicated in the occurrence of seizures in non-sclerotic patients, where the majority of principal and non-principal cells are preserved.

Summary Purpose: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1–2 antiepileptic drugs (AEDs). Methods: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n = 102) or once-daily ESL 400 mg (n = 100), 800 mg (n = 98), or 1,200 mg (n = 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). Results: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p = 0.0003) and 800-mg (p = 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56–62% of patients), lamotrigine (25–27%), and valproic acid (22–28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. Discussion: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.

Summary Purpose: To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods: This multicenter, double-blind, placebo-controlled trial randomized patients (age 16–70 years) with partial-onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8-week baseline, a 4-week titration, and a 12-week maintenance period. Results: Four hundred eighty-five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent-to-treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02), and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400 mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p

A tanulmány áttekinti azokat az érveket, amelyek szerint az alvás szakaszai sajátos mechanizmust képeznek a tanulási és emlékezeti konszolidáció számára. A REM-alvás szerepéről számos ellentmondó elképzelés született. Ugyanakkor az alvási _

A large proportion of hippocampal afferents and efferents are relayed through the subiculum. It is also thought to be a key structure in the generation and maintenance of epileptic activity; rhythmic interictal-like discharges were recorded in previous studies of subicular slices excised from temporal lobe epilepsy patients. In order to investigate if and how the subiculum is involved in the generation of epileptic discharges in vivo, subicular and lateral temporal lobe electrical activity were recorded under anesthesia in 11 drug-resistant epilepsy patients undergoing temporal lobectomy. Based on laminar field potential gradient, current source density, multiple unit activity (MUA) and spectral analyses, two types of interictal spikes were distinguished in the subiculum. The more frequently occurring spike started with an initial excitatory current (current source density sink) in the pyramidal cell layer associated with increased MUA in the same location, followed by later inhibitory currents (current source density source) and decreased MUA. In the other spike type, the initial excitation was confined to the apical dendritic region and it was associated with a less-prominent increase in MUA. Interictal spikes were highly synchronized at spatially distinct locations of the subiculum. Laminar data showed that the peak of the initial excitation occurred within 0-4 ms at subicular sites separated by 6 mm at the anterior-posterior axis. In addition, initial spike peak amplitudes were highly correlated in most recordings. A subset of subicular and temporal lobe spikes were also highly synchronous, in one case the subicular spikes reliably preceded the temporal lobe discharges. Our results indicate that multiple spike generator mechanisms exist in the human epileptic subiculum suggesting a complex network interplay between medial and lateral temporal structures during interictal epileptic activity. The observed widespread intra-subicular synchrony may reflect both of its intrinsic and extrinsically triggered activity supporting the hypothesis that subiculum may also play an active role in the distribution of epileptiform activity to other brain regions. Limited data suggest that subiculum might even play a pacemaker role in the generation of paroxysmal discharges.

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis.

Summary: Objective: To examine the effects of age on different aspects of temporal lobe seizure semiology. Methods: We performed a video analysis of 605 archived seizures from 155 consecutive patients (age 10 months to 49 years) selected by seizure freedom after temporal lobectomy. Eighty patients had hippocampal sclerosis (HS). Beside semiological seizure classification, we assessed age dependency of several axes of seizure semiology: (1) aura, (2) number of different lateralizing signs, occurrence of ictal (3) emotional signs, (4) autonomic symptoms, (5) automatisms, and (6) secondary generalization as well as (7) the ratio of motor seizure components. Results: From the 155 patients, 117 reported aura, 39 had ictal emotional signs, 51 had autonomic symptoms, 130 presented automatisms, while 18 patients showed secondary generalization at least once during their seizures. Altogether 369 (median: 2/patient) different lateralizing signs were recorded. Frequency of HS (p < 0.001), ictal automatisms (p < 0.001), secondary generalization (p = 0.014), number of different lateralizing signs (p < 0.001) increased while the ratio of motor seizure component (p = 0.007) decreased by age. Auras, emotional symptoms, and autonomic signs occurred independently of patients’ ages. Hippocampal sclerosis adjusted linear models revealed that the frequency of automatisms and secondarily generalized seizures as well as the number of different lateralizing signs are HSindependent significant variables. Conclusion: Our findings support that brain maturation significantly influences the evolution of some important aspects (motor seizures, lateralizing signs) of temporal lobe seizure semiology. Conversely, other aspects (aura, emotional, and autonomic signs) are independent of the maturation process. This is the first report investigating age dependency of epileptic seizure semiology comparing all age groups. Key Words: Temporal lobe epilepsy—Seizure semiology—Age.

Summary Objective To describe clinical characteristics and lateralizing value of peri-ictal electrode manipulation automatism (EMA) in patients with temporal lobe epilepsy (TLE) and compare our data with ictal manual automatisms described in the literature. Methods Two-hundred and five videotaped seizures of 55 consecutive patients with refractory TLE and postoperatively seizure-free outcome were analyzed and EMA (tugging, scratching or adjusting the electrodes and cables) were monitored. Results Twenty-eight (51%) patients showed EMA during 47 (23%) seizures. Ictal start was noted in 22 seizures and in 19/22 cases EMA finished before the end of seizure. Ictal EMAs were always associated with automotor seizure components. During 25 seizures, exclusively postictal EMAs were observed. Electrode manipulation was presented during 24/112 left-sided and 23/93 right-sided seizures ( p =0.742). Peri-ictal EMA was unilateral (completed by one hand) in 24/47 seizures (10 ictal, 14 postictal); it was done by the hand ipsilateral to the seizure onset zone in 17/24 and by contralateral hand in 7/24 cases ( p =0.064). We observed concomitant contralateral dystonic posturing during 3/10 seizures with unilateral ictal EMA. Unilateral hand automatism, temporally independent from the EMA appeared in 30 (64%) of the 47 seizures. Conclusion Peri-ictal EMA is a frequent phenomenon but shows no lateralizing value in TLE. The mechanism of EMA is in many ways dissimilar from that of earlier described manual automatisms.

Arousal systems play a topical neurophysiologic role in protecting and tailoring sleep duration and depth. When they appear in NREM sleep, arousal responses are not limited to a single EEG pattern but are part of a continuous spectrum of EEG modifications ranging from high-voltage slow rhythms to low amplitude fast activities. The hierarchic features of arousal responses are reflected in the phase A subtypes of CAP (cyclic alternating pattern) including both slow arousals (dominated by the