Effects of repeated postnatal administration of caffeine (10 and 20mg/kg s.c. daily from P7 to P11) were studied in two models of epileptic seizures characterized by spike-and-wave EEG rhythm in 18- and 25-day-old rats. Rhythmic metrazol activity (RMA, model of human absences) was induced by low dose of pentylenetetrazol (PTZ, 20mg/kg or 40mg/kg, i.p.) and minimal clonic seizures (model of human myoclonic seizures) by two successive doses of PTZ (20 and 40mg/kg i.p.). Early postnatal caffeine treatment resulted in significant changes of RMA only in 18-day-old rats. Anticonvulsant effects were observed in RMA episodes elicited by the 20-mg/kg dose of PTZ in both caffeine groups whereas latency of RMA episodes induced by the 40-mg/kg dose was shortened and their duration was prolonged. No changes were found in 25-day-old animals. Incidence, EEG and motor pattern of minimal clonic seizures were not changed. Some animals in both control age groups exhibited transition to generalized tonic-clonic seizures. This type of seizures never appeared in caffeine-treated 25-day-old animals. Mixed effects of postnatal caffeine exposure were demonstrated; these predominantly anticonvulsant effects are age- and model-specific.

• MeSH
• analýza rozptylu MeSH
• elektroencefalografie MeSH
• kofein * farmakologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• novorozená zvířata MeSH
• pentylentetrazol * MeSH
• periodicita MeSH
• potkani Wistar MeSH
• reakční čas účinky léků   MeSH
• stimulanty centrálního nervového systému * farmakologie   MeSH
• věkové faktory MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• záchvaty * chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.

• MeSH
• algoritmy MeSH
• biologické markery MeSH
• elektrokortikografie MeSH
• epilepsie parciální diagnóza   MeSH
• lidé MeSH
• modely neurologické MeSH
• mozek patofyziologie   MeSH
• rizikové faktory MeSH
• záchvaty diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

BACKGROUND: Postnatal treatment with caffeine from P7 to P11 (10 or 20 mg/kg daily) resulted in transient changes in two pentylenetetrazole (PTZ)-induced models of epileptic seizures characterized by spike-and-wave EEG rhythm in immature rats. To know if some changes persist into adulthood we studied these models in young adult Wistar rats. METHODS: Caffeine treatment at a daily dose of 10 and/or 20 mg/kg, sc was executed during postnatal days 7-11. Rhythmic metrazol activity (RMA, model of human absences) was induced in 60-day old rats by two successive doses of PTZ (20 + 20 mg/kg, ip) while for induction of minimal clonic seizures (model of human myoclonic seizures) the second dose of PTZ was 40 mg/kg. RESULTS: RMA episodes elicited by the 20 + 20 mg/kg dose of PTZ in adult rats exposed to caffeine at P7 to P11 were decreased. This effect was more pronounced in group treated with the higher dose of caffeine. In contrast, the lower dose of caffeine exacerbated minimal clonic seizures (both incidence and intensity were increased). In addition, some animals from the 20-mg/kg caffeine group exhibited transition to generalized tonic-clonic seizures. CONCLUSION: Different effects of postnatal caffeine exposure persist into adulthood; the seizure ameliorating effects in a model of absences and seizure exacerbating action in a model of myoclonic seizures are dose-specific.

• MeSH
• absentní epilepsie chemicky indukované   farmakoterapie   MeSH
• epilepsie myoklonické chemicky indukované   farmakoterapie   MeSH
• kofein aplikace a dávkování   terapeutické užití   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• pentylentetrazol * MeSH
• stárnutí * účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

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

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

The mechanism of seizure emergence and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. We found that the transition to seizure is not a sudden phenomenon, but is instead a slow process that is characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon that is observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We found that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.

• MeSH
• elektroencefalografie MeSH
• hipokampální oblast CA1 patofyziologie   MeSH
• hipokampus patofyziologie   MeSH
• lidé MeSH
• nervová síť patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• synapse fyziologie   MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dynamics underlying epileptic seizures span multiple scales in space and time, therefore, understanding seizure mechanisms requires identifying the relations between seizure components within and across these scales, together with the analysis of their dynamical repertoire. In this view, mathematical models have been developed, ranging from single neuron to neural population. In this study, we consider a neural mass model able to exactly reproduce the dynamics of heterogeneous spiking neural networks. We combine mathematical modeling with structural information from non invasive brain imaging, thus building large-scale brain network models to explore emergent dynamics and test the clinical hypothesis. We provide a comprehensive study on the effect of external drives on neuronal networks exhibiting multistability, in order to investigate the role played by the neuroanatomical connectivity matrices in shaping the emergent dynamics. In particular, we systematically investigate the conditions under which the network displays a transition from a low activity regime to a high activity state, which we identify with a seizure-like event. This approach allows us to study the biophysical parameters and variables leading to multiple recruitment events at the network level. We further exploit topological network measures in order to explain the differences and the analogies among the subjects and their brain regions, in showing recruitment events at different parameter values. We demonstrate, along with the example of diffusion-weighted magnetic resonance imaging (dMRI) connectomes of 20 healthy subjects and 15 epileptic patients, that individual variations in structural connectivity, when linked with mathematical dynamic models, have the capacity to explain changes in spatiotemporal organization of brain dynamics, as observed in network-based brain disorders. In particular, for epileptic patients, by means of the integration of the clinical hypotheses on the epileptogenic zone (EZ), i.e., the local network where highly synchronous seizures originate, we have identified the sequence of recruitment events and discussed their links with the topological properties of the specific connectomes. The predictions made on the basis of the implemented set of exact mean-field equations turn out to be in line with the clinical pre-surgical evaluation on recruited secondary networks.

• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The aim of this study was to determine if behavioral patterns during the postictal state depend on the type of seizure. METHODS: Rhythmic electrical stimulation of sensorimotor cortex can elicit two types of epileptic afterdischarges (ADs) in adult rats: the spike-and-wave type accompanied by clonic convulsions, and a transition to a nonconvulsive type characterized by behavioral automatisms (mixed type). Rats in which stimulation did not induce ADs constituted the control group. The behavior of the animals was recorded for 20 minutes after the end of ADs or stimulation. RESULTS: Stimulation elicited only shortlasting minimal changes in control rats. Spike-and-wave ADs led to alternation of normal and unsteady walking, a decrease in normal sitting and lying (rigid lying appeared instead), and wet dog shakes (WDS). Mixed-type ADs abolished normal walking and sitting and induced unsteady walking, rigid lying, and a substantial number of WDS. CONCLUSIONS: Abnormal phenomena induced by the two types of ADs differ mostly quantitatively, but also qualitatively.

• MeSH
• chování zvířat fyziologie   MeSH
• chůze fyziologie   MeSH
• elektrická stimulace MeSH
• elektroencefalografie MeSH
• epilepsie patofyziologie   psychologie   MeSH
• financování organizované MeSH
• implantované elektrody MeSH
• krysa rodu rattus MeSH
• limbický systém fyziologie   MeSH
• mozková kůra patofyziologie   MeSH
• péče o zevnějšek u zvířat fyziologie   MeSH
• potkani Wistar MeSH
• refrakterní doba elektrofyziologická fyziologie   MeSH
• thalamus fyziologie   MeSH
• záchvaty patofyziologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

Status epilepticus (SE) in developing rats leads to neuronal degeneration in many brain structures including neocortex but the functional consequences of cortical damage were studied only exceptionally. Lithium-pilocarpine SE was elicited in 12- (P12) and 25-day-old (P25) rats, convulsions were interrupted after 2h by paraldehyde. Cortical electrodes were implanted 3, 6, 9, 13 and/or 26 days after SE. Low-frequency stimulation of sensorimotor cortex was repeated with at least 10-min intervals with a stepwise increasing intensity (0.2-14 mA). Thresholds for movements elicited by stimulation, spike-and-wave afterdischarges (ADs), clonic seizures, mixed ADs (transition into a limbic type of ADs) and recurrent ADs as well as duration of ADs were evaluated. The first three phenomena were not influenced by SE with the exception of lower thresholds for movements during stimulation. Transition into limbic seizures and recurrent seizures were delayed in both age groups and threshold intensities for limbic ADs were at some intervals higher in SE than in control animals. Duration of ADs was changed only at short intervals after SE; it was shortened at 3 and 6 days in P25 and 3 days in P12 rats, respectively. P12 group then exhibited a transient increase in duration of ADs 6 days after SE. Our results did not prove a higher cortical excitability after SE in either age group. On the contrary, there were some signs of a decreased excitability.

• MeSH
• elektrická stimulace MeSH
• elektroencefalografie MeSH
• epilepsie tonicko-klonická patofyziologie   MeSH
• financování organizované MeSH
• konvulziva MeSH
• krysa rodu rattus MeSH
• lithiumkarbonát MeSH
• longitudinální studie MeSH
• mozková kůra patofyziologie   MeSH
• pilokarpin MeSH
• pohyb fyziologie   MeSH
• pohybová aktivita fyziologie   MeSH
• potkani Wistar MeSH
• stárnutí fyziologie   MeSH
• status epilepticus chemicky indukované   patofyziologie   psychologie   MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

The role of inhibitory γ-aminobutyric acid-A (GABA-A) system in the cortical epileptic afterdischarges (ADs) was studied at three different developmental stages of rats. Animals 12, 18 and 25days old with implanted epidural electrodes were pretreated with bicuculline (1 and 2mg/kgi.p.) and 15min later repeatedly stimulated with low frequency trains with stepwise increasing current intensity. Bicuculline only exceptionally decreased threshold current intensities necessary for elicitation of movements directly bound to stimulation, spike-and wave ADs, clonic seizures and transition into a limbic type of ADs. Duration of ADs was not systematically affected by either dose of bicuculline. In contrast, transcallosal evoked potentials exhibited under the influence of bicuculline steeper curve expressing relation between intensity of stimuli and amplitude of responses. In contrast to GABA-B receptors, GABA-A receptors do not play an important role in generation and arrest of cortical epileptic ADs in immature rats.

• MeSH
• bikukulin farmakologie   MeSH
• elektrická stimulace MeSH
• evokované potenciály účinky léků   fyziologie   MeSH
• GABA antagonisté farmakologie   MeSH
• implantované elektrody MeSH
• krysa rodu rattus MeSH
• mozková kůra účinky léků   patofyziologie   MeSH
• potkani Wistar MeSH
• receptory GABA-A fyziologie   MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Autor se zamýšlí nad úskalími diferenciální diagnostiky mezi migrénami, především pak s aurou, a epilepsiemi ložiskovými (fokálními, parciálními) idiopatickými, zejména potom věkově vázanými benigními. Tyto diagnózy patří v ambulantní praxi dětského neurologa k nejčastějším. Poukazuje na podobnost obou jednotek z pohledu anamnestických údajů, klinických obrazů i normálních výsledků pomocných vyšetření včetně strukturálních zobrazení mozku, upozorňuje rovněž na obdobné terapeutické postupy a prognostické aspekty. Rozhodujícím rozlišujícím vyšetřením zůstává EEG, přičemž správná interpretace nálezů ve smyslu elektro-klinické korelace nemusí být mnohdy vůbec jednoznačná. Autor rovněž zdůrazňuje, že diagnostické rozvahy mohou být značně komplikovány jejich současným výskytem nebo vzájemnými přechody v čase u téhož pacienta či případnými kombinacemi s dalšími neepileptickými záchvaty, což v dětském věku určitě není ničím neobvyklým. Uvedené se týká nejen klinických obrazů, které především v nejnižších věkových kategoriích jsou mnohdy atypické a děti navíc často nedokáží své potíže relevantně popsat, ale také EEG vzorců.

The author discusses the pitfalls of differential diagnosis between migraines, particularly those with aura, and idiopathic focal (partial) epilepsies, particularly benign, age-related ones. These diagnoses are among the most common in the outpatient practice of a paediatric neurologist. The author points out to the similarity of both entities in terms of medical history data, clinical presentations, and normal results of auxiliary examinations, including structural brain imaging, and highlights the similar therapeutic strategies and prognostic aspects. EEG remains a decisive examination tool for distinction; nevertheless, correct interpretation of findings in terms of electroclinical correlation may not always be unequivocal. The author also emphasizes that diagnostic considerations may be greatly complicated by their concurrent presence or mutual transitions over time in the same patient, or by possible combinations with other non-epileptic seizures, which is not an uncommon occurrence in paediatric age. The above applies not only to clinical presentations that, particularly in the lowest age groups, are often atypical, with children being frequently unable to describe their complaints in a relevant way, but also to EEG patterns.

• Klíčová slova
• diferenciální diagnostika, dětský věk,
• MeSH
• ambulantní péče MeSH
• bolesti hlavy etiologie   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• elektroencefalografie MeSH
• epilepsie diagnóza   MeSH
• lidé MeSH
• migréna diagnóza   MeSH
• záchvaty etiologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH