Epileptic Activity In Patients Research Articles

Antiepileptic Drugs and Their Dual Mechanism of Action on Carbonic Anhydrase.

(1) Background: The benefit of using inhibitors of carbonic anhydrase (CA), such as acetazolamide, in the treatment of epilepsy has previously been described. (2) Methods: In this paper, the effect on CA of the most well-known antiepileptic drugs was studied in vitro and in vivo. The effects, after chronic treatment, of carbamazepine, phenytoin, valproate, primidone, clonazepam, and ethosuximide were studied in vitro on purified CA, isozyme I (CA I) and CA, and isozyme II (CA II) activity and in vivo on epileptic erythrocyte CA I and CA II activity. (3) Results: In vitro results showed that all antiepileptic drugs reduced purified CA II activity according to dose–response relationships and slightly inhibited CA I activity. In vivo results showed that the chronic administration of antiseizure drugs induced a progressive reduction in erythrocyte CA II activity in all the groups studied. This study shows that CA II inhibition can be induced both in vitro and in vivo by major antiepileptic agents as it might be one of the effective mechanisms of these anticonvulsant drugs. (4) Conclusions: The decrease in CA II activity in epileptic patients after antiseizure treatment suggests the involvement of CA II in the pathogenesis of epilepsy.

Mozart effect in epilepsy: Why is Mozart better than Haydn? Acoustic qualities‐based analysis of stereoelectroencephalography

We aimed to confirm the Mozart effect in epileptic patients using intracerebral electroencephalography recordings and the hypothesis that the reduction of epileptiform discharges (EDs) can be explained by the music's acoustic properties. Eighteen epilepsy surgery candidates were implanted with depth electrodes in the temporal medial and lateral cortex. Patients listened to the first movement of Mozart's Sonata for Two Pianos K. 448 and to the first movement of Haydn's Symphony No. 94. Musical features from each composition with respect to rhythm, melody, and harmony were analyzed. Epileptiform discharges in intracerebral electroencephalography were reduced by Mozart's music. Listening to Haydn's music led to reduced EDs only in women; in men, the EDs increased. The acoustic analysis revealed that nondissonant music with a harmonic spectrum and decreasing tempo with significant high-frequency parts has a reducing effect on EDs in men. To reduce EDs in women, the music should additionally be gradually less dynamic in terms of loudness. Finally, we were able to demonstrate that these acoustic characteristics are more dominant in Mozart's music than in Haydn's music. We confirmed the reduction of intracerebral EDs while listening to classical music. An analysis of the musical features revealed that the acoustic characteristics of music are responsible for suppressing brain epileptic activity. Based on our study, we suggest studying the use of musical pieces with well-defined acoustic properties as an alternative noninvasive method to reduce epileptic activity in patients with epilepsy.

Estimation of Bcl-2 and Ki-67 in Gingival Epithelium of Epileptic Patients

Abstract 
 
 Introduction: Gingival overgrowth is one of several oral side effects of phenytoin, a potent antiepileptic drug. Several mechanisms have been elucidated to understand the pathogenesis of drug induced gingival overgrowth. The frequency of gingival overgrowth associated with chronic phenytoin therapy remains controversial. and the possible subclinical effects of this drug on the gingival epithelium should be investigated histopathologically and immunohistochemically.
 Purpose of the study: To investigate the Bcl-2 for apoptosis rate and Ki-67 for the epithelial proliferative activity in epileptic patients.
 Materials and methods: Twenty four samples of gingival tissue from epileptic patients treated with phenytoin and in eight samples of gingival tissue from healthy patients who didn’t use phenytoin (control) were evaluated for Bcl-2 and Ki-67 immunohistochemically.
 Results: The results revealed moreproliferative activity of the overlying epithelium and an increased pattern of Bcl-2 and Ki-67 in phenytoin users compared to controls.
 Conclusion: These results concluded that the increased epithelial thickness observed in phenytoin induced gingival overgrowth is associated with increased apoptotic rate and mitotic activity , especially in the oral epithelium.
 
 Keywords: Gingival overgrowth, Bcl-2, Ki-67, Phenytoin.

The intrinsic cell type-specific excitatory connectivity of the developing mouse subiculum is sufficient to generate synchronous epileptiform activity.

The activity of local excitatory circuits of the subiculum has been suggested to be involved in the initiation of pathological activity in epileptic patients and experimental animal models of temporal lobe epilepsy. We have taken advantage of multimodal techniques to classify subicular cells in distinct subclasses and have investigated their morphofunctional properties and connectivity in vitro. Our results indicate that local subicular excitatory circuits are connected in a cell type-specific fashion and that synapses are preferentially established on basal vs. apical dendrites. We show that local excitatory circuits, isolated from extrasubicular inputs and pharmacologically disinhibited, are sufficient to initiate synchronous epileptiform activity in vitro. In conclusion, this work provides a high-resolution description of local excitatory circuits of the subiculum and highlights their mechanistic involvement in the generation of pathological activity. The subiculum has been suggested to be involved in the initiation of pathological discharges in human patients and animal models of temporal lobe epilepsy. Although converging evidence has revealed the existence of functional diversity within its principal neurons, much less attention has been devoted to its intrinsic connectivity and whether its local excitatory circuits are sufficient to generate epileptiform activity. Here, we have directly addressed these two key points in mouse subicular slices. First, using multivariate techniques, we have distinguished two groups of principal cells, which we have termed type1 and type2. These subgroups roughly overlap with what were classically indicated as regular and bursting cells, and showed differences in the extension and complexity of their apical dendrites. Functional connectivity was found both between similar (homotypic) and different (heterotypic) types of cells, with a marked asymmetry within heterotypic pairs. Unitary excitatory postsynaptic potentials (uEPSPs) revealed a high degree of variability both in amplitude, failure rate, rise time and half-width. Post hoc analysis of functionally connected pairs suggested that the observed uEPSPs were mediated by few contact sites, predominantly located on the basal dendrites. When surgically isolated from extrasubicular excitatory afferents, pharmacologically disinhibited subicular slices generated hyper-synchronous discharges. Thus, we conclude that local subicular excitatory circuits, connected according to cell type-specific rules, are sufficient to promote epileptiform activity. This conclusion fits well with a previous suggestion that local subicular events, purely mediated by excitatory connections, may underlie the pre-ictal discharges that govern interictal-ictal transitions.

Metformin Plus Caloric Restriction Show Anti-epileptic Effects Mediated by mTOR Pathway Inhibition.

Caloric restriction (CR) has anti-epileptic effects in different animal models, at least partially due to inhibition of the mechanistic or mammalian target of rapamycin (mTOR) signaling pathway. Adenosine monophosphate-activated protein kinase (AMPK) inhibits mTOR cascade function if energy levels are low. Since hyper-activation of mTOR participates in epilepsy, its inhibition results in beneficial anti-convulsive effects. A way to attain this is to activate AMPK with metformin. The effects of metformin, alone or combined with CR, on the electrical kindling epilepsy model and the mTOR cascade in the hippocampus and the neocortex were studied. Combined metformin plus CR beneficially affected many kindling aspects, especially those relating to generalized convulsive seizures. Therefore, metformin plus CR could decrease measures of epileptic activity in patients with generalized convulsive seizures. Patients that are obese, overweight or that have metabolic syndrome in addition to having an epileptic disease are an ideal population for clinical trials to test the effectiveness of metformin plus CR.

Network specific change in white matter integrity in mesial temporal lobe epilepsy

ObjectivesTo identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). MethodsWe recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. ResultsTractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. ConclusionThe change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation.

Altered Structural and Functional Feature of Striato-Cortical Circuit in Benign Epilepsy with Centrotemporal Spikes.

Benign epilepsy with centrotemporal spikes (BECT) is the most common form of childhood idiopathic focal epilepsy syndrome. We investigated quantitative evidence regarding brain morphology and functional connectivity features to provide insight into the neuroanatomical foundation of this disorder, using high resolution T1-weighted magnetic resonance imaging (MRI) and resting state functional MRI in 21 patients with BECT and in 20 healthy children. The functional connectivity analysis, seeded at the regions with altered gray-matter (GM) volume in voxel-based morphometry (VBM) analysis, was further performed. Then, the observed structural and functional alteration were investigated for their association with the clinical and behavior manifestations. The increased GM volume in the striatum and fronto-temporo-parietal cortex (striato-cortical circuit) was observed in BECT. The decreased connections were found among the motor network and frontostriatal loop, and between the default mode network (DMN) and language regions. Additionally, the GM of striatum was negatively correlated with age at epilepsy onset. The current observations may contribute to the understanding of the altered structural and functional feature of striato-cortical circuit in patients with BECT. The findings also implied alterations of the motor network and DMN, which were associated with the epileptic activity in patients with BECT. This further suggested that the onset of BECT might have enduring structural and functional effects on brain maturation.

Analysis of Electroencephalogram Background Activity in Epileptic Patients and Healthy Subjects Using Dispersion Entropy

Analysis of Electroencephalogram Background Activity in Epileptic Patients and Healthy Subjects Using Dispersion Entropy

Time-variant coherence between heart rate variability and EEG activity in epileptic patients: an advanced coupling analysis between physiological networks

Time-variant coherence analysis between the heart rate variability (HRV) and the channel-related envelopes of adaptively selected EEG components was used as an indicator for the occurrence of (correlative) couplings between the central autonomic network (CAN) and the epileptic network before, during and after epileptic seizures. Two groups of patients were investigated, a group with left and a group with right hemispheric temporal lobe epilepsy. The individual EEG components were extracted by a signal-adaptive approach, the multivariate empirical mode decomposition, and the envelopes of each resulting intrinsic mode function (IMF) were computed by using Hilbert transform. Two IMFs, whose envelopes were strongly correlated with the HRV’s low-frequency oscillation (HRV-LF; ≈0.1 Hz) before and after the seizure were identified. The frequency ranges of these IMFs correspond to the EEG delta-band. The time-variant coherence was statistically quantified and tensor decomposition of the time-frequency coherence maps was applied to explore the topography-time-frequency characteristics of the coherence analysis. Results allow the hypothesis that couplings between the CAN, which controls the cardiovascular-cardiorespiratory system, and the ‘epileptic neural network’ exist. Additionally, our results confirm the hypothesis of a right hemispheric lateralization of sympathetic cardiac control of the HRV-LF.

A novel method for analysis of EEG background activity in epileptic patients and healthy subjects using Hilbert transform

Hypothesising that non-linear analysis of Electroencephalogram (EEG) signals may provide clinicians with information for medical diagnosis and assessment of the applied therapy, we investigated the EEG background activity in normal and epileptic subjects using Hilbert Transform Scatter Plots (HTSPs). A visual inspection of HTSPs revealed distinct differences in the different physio-pathological states of the EEG. These differences were quantified employing Radial Distance Index (RDI), which is derived from the Central Tendency Measure (CTM) of the HTSP. The application of such a technique is justified by ascertaining the presence of non-linearity in the EEG time series through surrogate test. The false-positive rejection of the null hypothesis is eliminated by employing Welch window before the computation of the Fourier transform and randomising the phases, in the generation of the surrogate data. Receiver Operating Characteristic (ROC) analysis reveals that RDI can discriminate between seizure and non-seizure states with very high accuracy.

The Effects of Mozart’s Music on Interictal Activity in Epileptic Patients: Systematic Review and Meta-analysis of the Literature

Mozart's music has been shown to have promising effects on nervous system functions. In this study, the effects of Mozart's work on epilepsy were reviewed. Articles were obtained from a variety of sources. The results of 12 studies were extracted. Three different meta-analyses were performed to examine (i) the percentage of patients who had changes in their interictal epileptic discharges (IEDs) by music therapy; and the changes of IEDs (ii) during and (iii) after exposure to Mozart's music. Data analysis indicated that 84% of patients listening to Mozart's music showed a significant decrease in IEDs. In addition, IEDs were decreased during (31.24%) and after (23.74%) listening to Mozart's compositions. A noteworthy response to music therapy in patients with a higher intelligence quotient, generalized or central discharges, and idiopathic epilepsy was demonstrated. The effect of Mozart's music on epilepsy seems to be significant. However, more randomized control studies are needed to determine its clinical efficacy.

ICA Extracts Epileptic Sources from fMRI in EEG-Negative Patients: A Retrospective Validation Study

Simultaneous EEG-fMRI has proven to be useful in localizing interictal epileptic activity. However, the applicability of traditional GLM-based analysis is limited as interictal spikes are often not seen on the EEG inside the scanner. Therefore, we aim at extracting epileptic activity purely from the fMRI time series using independent component analysis (ICA). To our knowledge, we show for the first time that ICA can find sources related to epileptic activity in patients where no interictal spikes were recorded in the EEG. The epileptic components were identified retrospectively based on the known localization of the ictal onset zone (IOZ). We demonstrate that the selected components truly correspond to epileptic activity, as sources extracted from patients resemble significantly better the IOZ than sources found in healthy controls. Furthermore, we show that the epileptic components in patients with and without spikes recorded inside the scanner resemble the IOZ in the same degree. We conclude that ICA of fMRI has the potential to extend the applicability of EEG-fMRI for presurgical evaluation in epilepsy.

Continuous Electroencephalographic Monitoring in Critically Ill Patients

Continuous electroencephalography as a bedside monitor of cerebral activity has been used in a range of critically ill patients. This review compiles the indications, limitations, and strategies for continuous electroencephalography in the ICU. The authors searched the electronic MEDLINE database. References from articles of special interest were selected. Electroencephalographically-defined suppression is routinely used as the basis for titration of pharmacologic therapy in refractory status epilepticus and intracranial hypertension. The increasing use of continuous electroencephalography reveals a clinically underappreciated burden of epileptiform and epileptic activity in patients with primary acute neurologic disorders, and also in critically ill patients with acquired encephalopathy. Status epilepticus is reported with continuous electroencephalography in 1% to 10% of patients with ischemic stroke, 8% to 14% with traumatic brain injury, 10% to 14% with subarachnoid hemorrhage, 1% to 21% with intracerebral hemorrhage, and 30% of patients following cardiorespiratory arrest. These figures underscore the importance of continuous electroencephalography in the critically ill. The interpretation of continuous electroencephalography in the ICU is challenged by electroencephalography artifacts and the frequent subtle differences between ictal and interictal patterns.

Is Spreading Depolarization Characterized by an Abrupt, Massive Release of Gibbs Free Energy from the Human Brain Cortex?

In the evolution of the cerebral cortex, the sophisticated organization in a steady state far away from thermodynamic equilibrium has produced the side effect of two fundamental pathological network events: ictal epileptic activity and spreading depolarization. Ictal epileptic activity describes the partial disruption, and spreading depolarization describes the near-complete disruption of the physiological double Gibbs–Donnan steady state. The occurrence of ictal epileptic activity in patients has been known for decades. Recently, unequivocal electrophysiological evidence has been found in patients that spreading depolarizations occur abundantly in stroke and brain trauma. The authors propose that the ion changes can be taken to estimate relative changes in Gibbs free energy from state to state. The calculations suggest that in transitions from the physiological state to ictal epileptic activity to spreading depolarization to death, the cortex releases Gibbs free energy in a stepwise fashion. Spreading depolarization thus appears as a twilight state close to death. Consistently, electrocorticographic recordings in the core of focal ischemia or after cardiac arrest display a smooth transition from the initial spreading depolarization component to the later ultraslow negative potential, which is assumed to reflect processes in cellular death.

Seizure frequency and bioelectric brain activity in epileptic patients in stable and unstable atmospheric pressure and temperature in different seasons of the year – a preliminary report

Background and purposeAn epileptic seizure is a sum of exogenous and endogenous factors affecting an epileptic focus. The aim of the study was to examine the influence of changes in atmospheric pressure and temperature on the increase in the frequency of seizures and changes in EEG in epileptic patients. Material and methodsThe study included 30 epileptic patients (aged 19–54) reporting the influence of changes in weather conditions on the increase in the frequency of seizures for at least 2 years. EEG was performed twice each season at the time of stable and unstable weather conditions. ResultsIn stable and unstable weather conditions, epileptic changes in EEG were most often found in winter (in 43.3% and 63.3% of patients, respectively). Unstable weather conditions increased the proportion of patients with epileptic changes in EEG also in the other seasons. Unstable weather conditions caused an increase in the frequency of seizures in 40% of patients in spring, 43.3% in autumn, 40% in winter and in approximately 7% in summer. ConclusionsIn spring, autumn and winter, unstable weather conditions cause an increase in the frequency of seizures in almost half of the epileptic patients but only in 7% in summer. The increase in frequency of seizures in unstable weather conditions did not correspond in all patients with increase of changes in EEG. The higher proportion of epileptic patients with changes in EEG in unstable weather conditions in all seasons suggests an impact of these conditions on subclinical seizure discharges in this period.

Increased spike frequency during general anesthesia with etomidate for magnetoencephalography in patients with focal epilepsies

Magnetoencephalography (MEG) is used for focus localization in presurgical evaluation of patients with focal epilepsies. In this proof-of-concept study, general anesthesia with etomidate was used to improve effectiveness of MEG-recordings. MEG-recordings of six patients with focal epilepsy were performed before and after application of etomidate. Spike frequency and localization accuracy of MEG with general anesthesia were compared with spontaneous MEG. After application of etomidate, an increase in spike frequency occurred in all patients, and movement artifacts were prevented. In one patient, spikes could only be detected by invasive EEG but not by MEG. The results were in accordance with spontaneous MEG or presurgical hypotheses about localizations of neocortical foci in three patients. Dipole localizations were distributed over fronto-temporal areas in three patients with ipsilateral temporo-mesial focus hypotheses. Etomidate ameliorated spike yield and stopped movement artifacts during MEG recordings in patients with focal epilepsy. Localization results were especially accurate in patients with neocortical epilepsy. These results could facilitate larger studies on the usefulness and safety of general anesthesia with etomidate that record and localize epileptic activity in patients with focal epilepsy by MEG.

Role of Selenium on Calcium Signaling and Oxidative Stress-induced Molecular Pathways in Epilepsy

Epilepsy is one of the oldest neurological conditions known to humankind. It is known that oxidative stress and generation of reactive oxygen species are a cause and consequence of epileptic seizures. Although recent years have seen tremendous progress in the molecular biology and metabolism of selenium, we still know little about the cell type-specific and temporal pattern of selenium and its derivatives in the brain of epileptic humans and experimental animals. It has been suggested that some antiepileptic drug therapies such as valproic acid, deplete the total body selenium level and selenium-dependent glutathione peroxidase (GSH-Px) activity although therapy with a new epileptic drug, topiramate, activated GSH-Px activity in epileptic animals and humans. An observation of lower blood or tissue selenium level and GSH-Px activity in epileptic patients and animals compared to controls in recent publications may support the proposed crucial role of selenium level and GSH-Px activity in the pathogenesis of epilepsy. Selenium is incorporated into an interesting class of molecules known as selenoproteins that contain the modified amino acid, selenocysteine. There are signs of selenium and selenoprotein deficiency in the pathogenesis of epilepsy. In conclusion, there is convincing evidence for the proposed crucial role of selenium and deficiency of GSH-Px enzyme activity in epilepsy pathogenesis. Blood GSH-Px activities could be a reliable indicator of selenium deficiency in patients with epilepsy.

EEG‐fMRI study of the ictal and interictal epileptic activity in patients with eyelid myoclonia with absences

To investigate the blood oxygenation level-dependent (BOLD) signal changes correlated with ictal and interictal epileptic discharges using electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) in patients with eyelid myoclonia with absences (EMA) and then to explore the pathophysiological mechanisms of epileptic discharges and their effect on brain function. Four patients with EMA were investigated through the method of EEG-fMRI. The characteristics of BOLD signal changes linked to ictal and interictal epileptic discharges under different states of consciousness were explored. Seven sessions of EEG-fMRI scanning in the four patients were obtained. The main regions of activation included thalamus, mesial frontal cortex, middle parietal lobe, temporal lobe, insula, midline structures, and cerebellum. Deactivations were mainly in the anterior frontal lobe, posterior parietal lobe, and posterior cingulate gyrus. Thalamic BOLD change was predominantly activation in most of our cases. The distribution of activation associated with ictal epileptic discharges was wider, and the distribution of deactivation was closer to pericortex compared with the BOLD change linked with interictal epileptic discharges. The activation in the thalamus may be associated with generalized spike wave in EMA; the combination of different patterns of activation with consistent pattern of deactivations ("default" pattern) in patients with EMA may prognosticate different states of consciousness in response to ictal and interictal epileptic discharges.

Analysis of the dynamics and origin of epileptic activity in patients with tuberous sclerosis evaluated for surgery of epilepsy

Objective The epilepsies associated with the tuberous sclerosis complex (TSC) are very often refractory to medical therapy. Surgery for epilepsy is an effective alternative when the critical link between the localization of seizure onset in the scalp and a particular cortical tuber can be established. In this study we perform analysis of ictal and interictal EEG to improve such link. Methods The ictal and interictal recordings of four patients with TSC undergoing surgery for epilepsy were submitted to independent component analysis (ICA), followed by source analysis, using the sLORETA algorithm. The localizations obtained for the ictal EEG and for the average interictal spikes were compared. Results The ICA of ictal EEG produced consistent results in different events, and there was good agreement with the tubers that were successfully removed in three of the four patients (one patient refused surgery). In some patients there was a large discrepancy between the localization of ictal and interictal sources. The interictal activity produced more widespread source localizations. Conclusions The use of ICA of ictal EEG followed by the use of source analysis methods in four cases of epilepsy and TSC was able to localize the epileptic generators very near the lesions successfully removed in surgery for epilepsy. Significance The ICA of ictal EEG events may be a useful add-on to the tools used to establish the connection between epileptic scalp activity and the cortical tubers originating it, in patients with TSC considered for surgery of epilepsy.

EEG-fMRI study of the interictal epileptic activity in patients with partial epilepsy

To investigate Blood Oxygen Level Dependent (BOLD) responses to interictal epileptic discharges (IEDs) during EEG-correlated functional MRI (EEG-fMRI) in patients with partial epilepsy. We studied eight patients who had a diagnosis of partial epilepsy and active spiking on routine scalp EEG recording. Sessions of continuous EEG-fMRI were recorded, and spikes (identified after online artifact removal) were used as events in the fMRI analysis. Regions of BOLD signal change in response to interictal epileptic discharge were assessed and epileptogenic zone localization was electroclinically identified. Eight patients with partial epilepsy were recruited (6 males, 2 females, mean age 18.5, mean onset age range 0.5-29). Two who underwent EEG-fMRI were excluded from further analysis: one due to absence of epileptic discharges, the other due to excessive head motion. Eight sessions of EEG-fMRI scanning in 6 patients were obtained: 6 with activation and deactivation, one with activation only, and one with deactivation only. Focal activations corresponding to electroclinical localization occurred in 7 sessions, 5 of which were maximal. Maximally activated areas detected by EEG-fMRI in patients with partial epilepsy appear to be concordant with epileptogenic areas as defined by electroclinical localization data. In most patients with focal epilepsy, positive BOLD responses seem to be mainly in epileptogenic zones and the corresponding contralateral areas. Responses to deactivation seem less associated with IEDs. So EEG-fMRI is a useful tool to study the pathophysiological mechanisms of epilepsy and may assist in presurgical evaluation of epilepsy.