PURPOSE: The study aim was to evaluate pharmacotherapy effects and long-term seizure outcomes in patients with juvenile absence epilepsy (JAE) during a five-year follow-up period. The secondary aim was to identify factors from patient history and determine their influence on seizure control. METHOD: We retrospectively studied 46 patients with JAE in the period between 2006 and 2011. The age at seizure onset, onset seizure type, family history of epilepsy, status epilepticus in history, medication history, and the rate of seizure control were studied. RESULTS: There were 30 females (65.2%) and 16 males (34.8%) in the study. The mean age at seizure onset was 12.9±5.6 years (ranged from 3 to 28 years). In 30 patients (65.2%), seizure onset was with absences, in 15 patients (32.6%) with generalized tonic-clonic seizure (GTCS), and in 1 patient (2.2%) with absence status. In 43 patients (93.5%), GTCS occurred in the course of the disease. Family history for epilepsy was positive in 10 patients (21.7%). In the five-year follow-up period, seizure freedom (Group 1) was achieved in 7 patients (15.2%). In total, 22 patients (47.8%) were classified into the groups involving very poor seizure control and antiepileptic drug resistance (Groups 5 and 6). The mean number of antiepileptic drugs (AEDs) used in the course of the disease in appropriate therapeutic doses was 3.8±2.3 (1-10 AEDs). CONCLUSION: The study results show that almost half of JAE patients have poor seizure control with a high rate of pharmacoresistance. The outcome of JAE can be very uncertain.

• Klíčová slova
• Epilepsy, JAE, Juvenile absence epilepsy, Outcome, Seizure control, Therapy,
• MeSH
• absentní epilepsie farmakoterapie   patofyziologie   MeSH
• antikonvulziva terapeutické užití   MeSH
• centra terciární péče MeSH
• dítě MeSH
• dospělí MeSH
• kombinovaná farmakoterapie MeSH
• léková rezistence MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• záchvaty farmakoterapie   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikonvulziva MeSH

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.

• MeSH
• absentní epilepsie MeSH
• dítě MeSH
• dospělí MeSH
• epilepsie myoklonické MeSH
• léková rezistence MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myoklonická epilepsie juvenilní * farmakoterapie   epidemiologie   etiologie   patofyziologie   MeSH
• pohlavní dimorfismus * MeSH
• poruchy fotosenzitivity MeSH
• prognóza MeSH
• průřezové studie MeSH
• záchvaty MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: To investigate possible neuronal dysfunction of the thalamus in patients suffering from typical absence epilepsy, using magnetic resonance spectroscopy (MRS). Special attention was paid to levels of N-acetylaspartate (NAA) and creatine (Cr), and to the NAA/Cr ratio. METHODS: MRS was performed over the right and left thalamus in nine patients suffering from typical absence epilepsy, and in nine sex- and age-matched healthy controls. All patients and controls were examined using a standard MRS-CSI (chemical shift imaging) technique. RESULTS: Statistical analysis of the obtained data demonstrated a significantly lower thalamic NAA/Cr ratio in patients with typical absence epilepsy when compared to the healthy controls. Our MRS data showed symmetrical distribution of NAA/Cr ratio in the right and left thalamus within both the patient group and the group of healthy controls. No significant correlation between the patients' thalamic NAA/Cr values and the duration of the epilepsy or seizure frequency was revealed. CONCLUSIONS: The present MRS data clearly indicate neuronal dysfunction in the thalami of patients with typical absence epilepsy. In agreement with other recent MRS findings in different idiopathic generalized epilepsy syndromes, our results confirm the role of the thalamus as an important structure in the pathogenesis of typical absence epilepsy.

• MeSH
• absentní epilepsie patofyziologie   MeSH
• dospělí MeSH
• kreatin metabolismus   MeSH
• kyselina aspartová analogy a deriváty   metabolismus   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie * MeSH
• neurony fyziologie   MeSH
• studie případů a kontrol MeSH
• thalamus metabolismus   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kreatin MeSH
• kyselina aspartová MeSH
• N-acetylaspartate MeSH Prohlížeč

OBJECTIVE: Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta-analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs). METHODS: 322 participants with JME and 126 age and gender-matched controls completed the Barratt's Impulsiveness Scale (BIS-brief) alongside information on seizure history and AED use. We compared group BIS-brief scores and assessed associations of JME BIS-brief scores with seizure characteristics and AED adverse effects. RESULTS: The mean BIS-brief score in JME was 18.1 ± 4.4 compared with 16.2 ± 4.1 in controls (P = 0.0007). Elevated impulsivity was associated with male gender (P = 0.027), frequent absence seizures (P = 0.0004) and lack of morning predominance of myoclonus (P = 0.008). High impulsivity significantly increased the odds of a psychiatric adverse event on levetiracetam (P = 0.036), but not any other psychiatric or somatic adverse effects. INTERPRETATION: Trait impulsivity is elevated in JME and comparable to scores in personality and neurotic disorders. Increased seizure frequency and absence of circadian seizure pattern moderate BIS score, suggesting disruption of both cortico-striatal and thalamocortical networks as a shared mechanism between seizures and impulsivity in JME. These findings warrant consideration of impulsivity as a distinct target of intervention, and as a stratifying factor for AED treatment in JME, and perhaps other types of epilepsy. The role of impulsivity in treatment adherence and psychosocial outcome requires further investigation.

• MeSH
• dítě MeSH
• dospělí MeSH
• impulzivní chování * MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myoklonická epilepsie juvenilní psychologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Low-voltage-activated T-type calcium channels are essential contributors to the functioning of thalamocortical neurons by supporting burst-firing mode of action potentials. Enhanced T-type calcium conductance has been reported in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and proposed to be causally related to the overall development of absence seizure activity. Here, we show that calnexin, an endoplasmic reticulum integral membrane protein, interacts with the III-IV linker region of the Cav3.2 channel to modulate the sorting of the channel to the cell surface. We demonstrate that the GAERS missense mutation located in the Cav3.2 III-IV linker alters the Cav3.2/calnexin interaction, resulting in an increased surface expression of the channel and a concomitant elevation in calcium influx. Our study reveals a novel mechanism that controls the expression of T-type channels, and provides a molecular explanation for the enhancement of T-type calcium conductance in GAERS.

• MeSH
• absentní epilepsie genetika   MeSH
• kalnexin metabolismus   MeSH
• krysa rodu Rattus MeSH
• missense mutace * MeSH
• modely nemocí na zvířatech MeSH
• mutantní proteiny genetika   metabolismus   MeSH
• transport proteinů MeSH
• vápníkové kanály - typ T genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Cacna1h protein, rat MeSH Prohlížeč
• kalnexin MeSH
• mutantní proteiny MeSH
• vápníkové kanály - typ T MeSH

The aim of this study was to examine the development of cortical epileptic afterdischarges (ADs) in genetic absence epilepsy WAG/Rij rats, and to compare them with two strains with minimal incidence of spike-and-wave (SW) episodes (ACI and Wistar). Epileptic ADs were elicited by stimulation of sensorimotor cortex in 12-, 18-, and 25-day-old rats of the three strains. The threshold current intensities were established for movements accompanying stimulation, for ADs of the SW type and accompanying clonic seizures and for transition into limbic type of ADs (characterized by behavioral automatisms). Individual groups were formed by 7-12 rats. There were no differences among the three strains in the thresholds for elicitation of stimulation-bound movements. In contrast, WAG/Rij and ACI rats exhibited easier elicitation of SW ADs than Wistar rats at the age of 18 and 25 days. There was no difference among the three strains in transition into the limbic type of ADs in 18- and 25-day-old rats. Lower thresholds for SW ADs in 18- and 25-day-old WAG/Rij and ACI rats in comparison with Wistar rats are in agreement with our data from adult animals as well as with development of pharmacologically induced models of absence seizures. The failure to find a specific difference between WAG/Rij rats and the other two strains might indicate a difference in generation of SW episodes and SW cortical AD.

• MeSH
• absentní epilepsie chemicky indukované   genetika   patofyziologie   MeSH
• druhová specificita MeSH
• elektrická stimulace MeSH
• elektroencefalografie statistika a číselné údaje   MeSH
• inbrední kmeny potkanů fyziologie   MeSH
• krysa rodu Rattus MeSH
• limbický systém patofyziologie   MeSH
• modely genetické MeSH
• mozková kůra růst a vývoj   patofyziologie   MeSH
• nervové dráhy MeSH
• novorozená zvířata MeSH
• potkani inbrední ACI MeSH
• potkani Wistar fyziologie   MeSH
• thalamus patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.

• Klíčová slova
• classification, definition, drug resistance, juvenile myoclonic epilepsy, prognosis,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• absentní epilepsie komplikace   farmakoterapie   MeSH
• antikonvulziva terapeutické užití   MeSH
• bezvědomí farmakoterapie   etiologie   MeSH
• dítě MeSH
• elektroencefalografie MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• prognóza MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• antikonvulziva MeSH

• MeSH
• absentní epilepsie genetika   patofyziologie   MeSH
• dítě MeSH
• elektroencefalografie * MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• riziko MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• srovnávací studie MeSH

The action of ketamine was studied in two models of seizures: a) bilateral neocortical discharges produced by topical application of pentylenetetrazol (model of simple partial seizures); and b) rhythmic spike-and-wave activity induced by systemic administration of pentylenetetrazol (model of absence seizures). Ketamine exerted biphasic effects. In the first model, the dose of 20 mg/kg ketamine significantly suppressed the ictal neocortical discharges (i.e., continuous spiking or ictal activity) accompanied by clonic motor seizures. However, at the dose of 40 mg/kg ketamine significantly accentuated the onset and increased the number of individual discharges (interictal spikes) in bilateral neocortical foci. In the model of rhythmic spike-and-wave activity, the lower dose of ketamine (20 mg/kg) decreased the number of rhythmic spike-and-wave episodes when compared to the higher dose (40 mg/kg) of ketamine, which increased the number of episodes. However, neither result differed significantly from control values. The present results suggest a dose-dependent action of ketamine: Lower doses (10 and 20 mg/kg in the rat) are able to suppress seizure activity, whereas a higher dose (40 mg/kg) potentiates the seizures. Moreover, the action of ketamine may be dependent upon the seizure model used. The study presents a new model of acute epileptic focus in freely moving rats.

• MeSH
• absentní epilepsie chemicky indukované   patofyziologie   MeSH
• elektroencefalografie účinky léků   MeSH
• epilepsie parciální chemicky indukované   patofyziologie   MeSH
• injekce intraperitoneální MeSH
• injekce MeSH
• ketamin farmakologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra MeSH
• pentylentetrazol aplikace a dávkování   MeSH
• potkani Wistar 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
• Názvy látek
• ketamin MeSH
• pentylentetrazol MeSH