OBJECTIVE: To provide additional information on the transport of the new anti-seizure medications lacosamide, perampanel, and zonisamide in breast milk and breastfed infants. METHODS: Between 2013 and 2022, concentrations of anti-seizure medications were measured in six women with epilepsy (each drug in two patients) using high-performance liquid chromatography. Additionally, concentrations were determined after two consecutive pregnancies in women receiving lacosamide and one woman receiving zonisamide. In all cases, anti-seizure medication concentrations were measured in the maternal serum and breast milk, and five cases, in the infant serum. RESULTS: For lacosamide, the ratios of breast milk/maternal serum concentration varied between 0.77 and 0.93, the ratios of infant/maternal serum concentrations were 0.16 and 0.35, and the ratios of infant serum/milk concentrations were 0.21 and 0.38. For perampanel, the ratios of breast milk/maternal serum concentration were 0.01 and 0.10 and the ratio of infant/maternal serum concentration was 0.36. For zonisamide, the ratios of breast milk/maternal serum concentration varied between 0.76 and 1.26, the ratios of infant/maternal serum concentrations between 0.44 and 0.85, and the ratios of infant serum/milk concentrations between 0.55 and 1.05. CONCLUSIONS: Breastfeeding is recommended for women using lacosamide, perampanel, and zonisamide. However, the actual exposure can only be accurately evaluated by determining the serum concentration of anti-seizure medication in breastfed infants.

• Klíčová slova
• Breastfeeding, Concentration, Lacosamide, Monitoring, Perampanel, Zonisamide,
• MeSH
• kojenec MeSH
• kojení * škodlivé účinky   MeSH
• lakosamid MeSH
• lidé MeSH
• nitrily * MeSH
• pyridony * MeSH
• těhotenství MeSH
• zonisamid MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lakosamid MeSH
• nitrily * MeSH
• perampanel MeSH Prohlížeč
• pyridony * MeSH
• zonisamid MeSH

PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS. METHODS: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13). The typing of HS was performed according to ILAE consensus classification, and patients were additionally sorted into subgroups based on the severity of neuronal depletion (Wyler grading system). Differences between patients with MTLE-HS with and without a history of febrile seizures were also assessed. RNA was isolated from native samples, and real-time gene expression analysis of cytokine-chemokine profiles, i.e., levels of IL-1β, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology. RESULTS: Upregulation of IL-1β (p = 0.001), IL-18 (p = 0.0018), CCL2 (p = 0,0377), CCL3 (p < 0.001), and CCL4 (p < 0.001) in MTLE-HS patients was detected when compared to the post-mortem hippocampal samples collected from autopsy controls. The STAT3 expression was higher in more severe neuronal loss and glial scaring determined by different Wyler grades in HS patients. Furthermore, cytokine-chemokine profiles were not different in MTLE-HS patients with or without febrile seizures. CONCLUSION: The upregulation of specific cytokines and chemokines in MTLE-HS provides evidence that the neuroinflammatory process contributes to MTLE epileptogenesis. History of febrile seizures did not alter the immune profiles. Specific immune mediators and related immune pathways represent potential therapeutic targets for seizure control and pharmacoresistancy prevention in MTLE associated with hippocampal sclerosis.

• Klíčová slova
• Chemokine, Cytokine, Epileptogenesis, Hippocampal sclerosis, Immune response, Interleukin, Pharmaco-resistant, Temporal lobe epilepsy,
• MeSH
• chemokiny metabolismus   MeSH
• cytokiny metabolismus   MeSH
• epilepsie temporálního laloku * komplikace   MeSH
• hipokampus patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• skleróza patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokiny MeSH
• cytokiny MeSH

Perampanel is a new antiepileptic drug with unique mechanism of action - antagonism of AMPA receptors. Its action in immature animals is not yet sufficiently known therefore we started to study anticonvulsant action of perampanel pretreatment (1-20 mg/kg i.p.) against seizures elicited by pentylenetetrazol. Three age groups of rats were examined - 12, 18 and 25 days old. Perampanel selectively suppressed the tonic phase of generalized seizures in the two younger groups and whole tonic-clonic seizures in the 25-day-old group. It exhibited also an anticonvulsant action against minimal clonic seizures present in control 18- and 25-day-old rats. Perampanel is an effective anticonvulsant drug even at very early stages of brain development.

• Klíčová slova
• AMPA receptors, Pentylenetetrazol, Perampanel, Postnatal development, Rat,
• MeSH
• antikonvulziva farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• nitrily MeSH
• pentylentetrazol toxicita   MeSH
• potkani Wistar MeSH
• pyridony MeSH
• záchvaty * chemicky indukované   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikonvulziva MeSH
• nitrily MeSH
• pentylentetrazol MeSH
• perampanel MeSH Prohlížeč
• pyridony MeSH

PURPOSE: Despite documented clinical effectiveness, deep brain stimulation (DBS) therapy for drug-resistant epilepsy rarely yields long-term seizure free outcomes. METHODS: This pilot study in five patients investigated circuit of Papez evoked potentials (EPs) using hippocampal sensing during anterior nucleus of the thalamus (ANT) electrical stimulation. We hypothesize that hippocampal EP is a potential biomarker that could be useful for ANT electrode targeting and improving seizure reduction. We obtained bilateral circuit of Papez EPs in five patients with bilateral temporal lobe epilepsy (TLE). The circuit of Papez EPs were measured and assessed by signal amplitude. Volumetric analysis of relevant mesial temporal structures and ANT stimulation analysis was performed on immediate post-implantation images. RESULTS: The patient with the most favorable seizure outcome, which meant long-term seizure reduction greater than 50 % compared to baseline, had strong bilateral EPs and normal hippocampal structure. Conversely, those without clinical benefit with ANT DBS had absent or weak bilateral EPs as well as MRI findings consistent with mesial temporal sclerosis (MTS). CONCLUSION: The data support the hypothesis that hippocampal EPs with ANT stimulation may be used to as a surrogate marker to probe circuit of Papez and predict ANT DBS efficacy.

• Klíčová slova
• Anterior nucleus of thalamus, Deep brain stimulation, Epilepsy, Evoked potentials, Mesial temporal sclerosis,
• MeSH
• dospělí MeSH
• elektrická stimulace MeSH
• epilepsie temporálního laloku patofyziologie   MeSH
• evokované potenciály fyziologie   MeSH
• hipokampus patofyziologie   MeSH
• lidé MeSH
• nervové dráhy patofyziologie   MeSH
• nuclei anteriores thalami patofyziologie   MeSH
• pilotní projekty MeSH
• záchvaty patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Infantile spasms (IS) is a developmental and epileptic encephalopathy with heterogeneous etiologies including many genetic causes. Genetic studies have identified pathogenic variants in over 30 genes as causes of IS. Many of these genetic causes are extremely rare, with only one reported incidence in an individual with IS. To better understand the genetic landscape of IS, we used targeted sequencing to screen 42 candidate IS genes and 53 established developmental and epileptic encephalopathy genes in 92 individual with IS. We identified a genetic diagnosis for 7.6% of our cohort, including pathogenic variants in KCNB1 (n = 2), GNAO1 (n = 1), STXBP1 (n = 1), SLC35A2 (n = 1), TBL1XR1 (n = 1), and KIF1A (n = 1). Our data emphasize the genetic heterogeneity of IS and will inform the diagnosis and management of individuals with this devastating disorder.

• Klíčová slova
• Epilepsy, Genetic diagnosis, Infantile spasms, Targeted sequencing, West syndrome,
• MeSH
• draslíkové kanály Shab genetika   MeSH
• kineziny genetika   MeSH
• kojenec MeSH
• křeče u dětí diagnóza   genetika   MeSH
• lidé MeSH
• mutace genetika   MeSH
• předškolní dítě MeSH
• proteiny přenášející monosacharidy genetika   MeSH
• proteiny vázající GTP - alfa-podjednotky Gi-Go genetika   MeSH
• receptory cytoplazmatické a nukleární genetika   MeSH
• represorové proteiny genetika   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslíkové kanály Shab MeSH
• GNAO1 protein, human MeSH Prohlížeč
• KCNB1 protein, human MeSH Prohlížeč
• KIF1A protein, human MeSH Prohlížeč
• kineziny MeSH
• proteiny přenášející monosacharidy MeSH
• proteiny vázající GTP - alfa-podjednotky Gi-Go MeSH
• receptory cytoplazmatické a nukleární MeSH
• represorové proteiny MeSH
• TBL1XR1 protein, human MeSH Prohlížeč
• UDP-galactose translocator MeSH Prohlížeč

Possible proconvulsant action of GABAB receptor antagonist CGP46381 was studied 3 and 13 days after status epilepticus elicited in 12-day-old rats. GABAA-dependent activity was tested by pentylenetetrazol administration and found different in 15-day-old rats after status epiolepticus but not in the older group. The interaction of the two GABAergic systems should be studied in detail.

• Klíčová slova
• CGP46381, Immature rats, Pentylenetetrazol, Status epilepticus,
• MeSH
• konvulzíva terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• kyseliny fosfinové terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• novorozená zvířata MeSH
• pentylentetrazol toxicita   MeSH
• pilokarpin toxicita   MeSH
• potkani Wistar MeSH
• receptory GABA-B - antagonisté terapeutické užití   MeSH
• status epilepticus chemicky indukované   farmakoterapie   MeSH
• věkové faktory 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
• 3-amino-2-hydroxypropylcyclohexylmethylphosphinic acid MeSH Prohlížeč
• konvulzíva MeSH
• kyseliny fosfinové MeSH
• pentylentetrazol MeSH
• pilokarpin MeSH
• receptory GABA-B - antagonisté MeSH

We reviewed the current RF-ablation technique for mTLE and complications relating to the procedure. RF-ablation of the amygdalohippocampal complex (AHC) is a stereotactic technique, performed under local anesthesia, which achieved long-term seizure-free clinical seizure outcomes in 71% of mTLE patients. Occipital access is used and thermolesions are made from a single trajectory in the long axis of the AHC. RF-ablation has shown a low complication rate and clinical seizure outcomes seem to be comparable with open surgical techniques.

• Klíčová slova
• Complication, Epilepsy surgery, Stereotactic amygdalohippocampectomy,
• MeSH
• epilepsie temporálního laloku diagnostické zobrazování   chirurgie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   chirurgie   MeSH
• neurochirurgové psychologie   MeSH
• radiofrekvenční ablace metody   MeSH
• stereotaktické techniky MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

In this article, we provide an overview of the reasons for the introduction of less invasive treatment modalities in the management of intractable mesial temporal lobe epilepsy (mTLE). We summarize our published research on stereotactic amygdalohippocampectomy (SAHE) and recalculate our data for the patients' last visit. In our previous work, we found that patients achieved long-term seizure-free outcomes in 70.5%. Re-analysis of results in a subgroup of patient who were diagnosed and followed-up at Epilepsy Center, Na Homolce Hospital, Prague, indicate that these outcomes are durable. Re-treatment in treatment failures was successful in all cases. The discussion compares novel treatment options and defines the place of SAHE among them.

• Klíčová slova
• Epilepsy surgery, Minimally invasive surgery, Stereotactic amygdalohippocampectomy,
• MeSH
• amygdala chirurgie   MeSH
• databáze faktografické statistika a číselné údaje   MeSH
• elektroencefalografie MeSH
• epilepsie temporálního laloku diagnostické zobrazování   chirurgie   MeSH
• hipokampus chirurgie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• počítačové zpracování obrazu MeSH
• radiofrekvenční ablace metody   MeSH
• výsledek terapie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Concern about postoperative worsening of cognitive functions after temporal lobe epilepsy surgery is an important issue. In this article we review our data on neuropsychological outcome after radiofrequency (RF) ablation of amygdalohippocampal complex (AHC). On a group level we found initial improvement in intelligence domains and unchanged memory scores one year after the surgery. During longitudinal follow-up, we found improvement in both intellectual and memory domains. This improvement was most pronounced up to two years after surgery. On an individual level, no patient worsened in any intellectual domain and most patients improved in memory. We hypothesize that this favorable outcome may be a consequence of minimization of collateral damage and incomplete destruction of target structures. We also summarize our experience with psychiatric complications of the procedure.

• Klíčová slova
• Intelligence, Memory, Neuropsychological assessment, Stereotactic amygdalohippocampectomy, WADA test,
• MeSH
• amygdala chirurgie   MeSH
• epilepsie temporálního laloku komplikace   chirurgie   MeSH
• hipokampus chirurgie   MeSH
• lidé MeSH
• mentální retardace etiologie   chirurgie   MeSH
• neuropsychologické testy MeSH
• poruchy paměti etiologie   chirurgie   MeSH
• radiofrekvenční ablace metody   MeSH
• výsledek terapie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Prenatal stress and drug exposure induce permanent alterations of the brain. Even though different brain structures are involved, alterations almost always refer to the hippocampus. The aim of this study was to investigate the excitability of hippocampal slices in low-magnesium epilepsy model of prenatally methamphetamine (MA, 5mg/kg sc.) or saline (sc., stress model) exposed animals in adult male rats. The second aim was to investigate, if a low dose of MA (1ml/kgs.c.) administered in adulthood changes the hippocampal activity of these animals. Adult Wistar male rats were divided into groups according to their prenatal treatment (C - naïve control; Sa - saline; MA - MA administration). One half of the animals was treated with a challenge dose of MA (1mg/kg sc.) 45min before hippocampal slices were cut. The activity of 350μ thick transversal slices of CA1 hippocampi was recorded (latencies of the first epileptiform discharge and the regular epileptiform activity) and evaluated in ACSF with low-magnesium concentration. Effects of prenatal exposure: The highest excitability was found in the Sa (prenatally stressed) group in respect to C and MA groups. This group developed also the highest number of seizure-like events. In addition, the prenatally MA treated group had also higher excitability than C group. Effects of the MA challenge dose: The challenge dose decreased the excitability of prenatally SA- exposed group. To conclude, even a mild prenatal stress significantly increases hippocampal excitability in adulthood and a challenge dose of MA is able to dampen it.

• Klíčová slova
• Excitability, Hippocampal slice, Low-magnesium epilepsy model, Methamphetamine, Prenatal stress, Rat,
• MeSH
• epilepsie etiologie   patofyziologie   MeSH
• hipokampus účinky léků   růst a vývoj   patofyziologie   MeSH
• methamfetamin toxicita   MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• nedostatek hořčíku MeSH
• potkani Wistar MeSH
• psychický stres * patofyziologie   MeSH
• techniky tkáňových kultur MeSH
• těhotenství MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methamfetamin MeSH