Seizure Intensity Research Articles

Teratogenic and anticonvulsant effects of zinc and copper valproate complexes in zebrafish

Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum across all types of seizures and epileptic syndromes. Unfortunately, approximately 30% of epileptic patients are refractory to the classical AED. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. In this preliminary study, we assess the embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, a derivative of valproic acid and the N-donor ligand in an adult zebrafish epileptic seizure model induced by pentylenetetrazole. The most toxic complex was [Cu(Valp)2Bipy], in which the LC50 was 0.22 μM at 48 h post fertilization (HPF) and 0.12 μM at 96 HPF, followed by [Zn(Valp)2Bipy] (LC50 = 10 μM). These same metallodrugs ([Cu(Valp)2Bipy] 10 mM/kg and [Zn(Valp)2Bipy] 30 mM and 100 mM/kg) displayed superior activity, thus reducing the seizure intensity by approximately 20 times compared to sodium valproate (175 mM/kg). Overall, [Cu(Valp)2Bipy] showed the best anticonvulsant effects. However, because of the toxicity of copper, [Zn(Valp)2Bipy] is considered the most promising anticonvulsant for future studies.

Volumetric response of the adult brain to seizures depends on the developmental stage when systemic inflammation was induced

Inflammation has detrimental influences on the developing brain including triggering the epileptogenesis. On the other hand, seizure episodes may induce inflammatory processes and further increase of brain excitability. The present study focuses on the problem whether transitory systemic inflammation during developmental period may have critical importance to functional and/or structural features of the adult brain. An inflammatory status was induced with lipopolysaccharide (LPS) in 6- or 30-day-old rats. Two-month-old rats which experienced the inflammation and untreated controls received injections of pilocarpine, and the intensity of their seizure behavior was rated during a 6-hour period. Three days thereafter, the animals were perfused; their brains were postfixed and subjected to magnetic resonance imaging (MRI) scans. Then, volumes of the brain and of its main regions were assessed. LPS injections alone performed at different developmental stages led to different changes in the volume of adult brain and also to different susceptibility to seizures induced in adulthood. Moreover, the LPS pretreatments modified different volumetric responses of the brain and of its regions to seizures. The responses showed strong inverse correlations with the intensity of seizures but exclusively in rats treated with LPS on postnatal day 30. It could be concluded that generalized inflammation elicited at developmental stages may have strong age-dependent effects on the adult brain regarding not only its susceptibility to action of a seizuregenic agent but also its volumetric reactivity to seizures.

PLPP/CIN Regulates Seizure Activity by the Differential Modulation of Calsenilin Binding to GluN1 and Kv4.2 in Mice.

Calsenilin (CSEN) binds to Kv4.2 (an A-type K+ channel) as well as N-methyl-D-aspartate receptor (NMDAR), and modulates their activities. However, the regulatory mechanisms for CSEN-binding to Kv4.2 or NMDAR remain elusive. Here, we demonstrate the novel role of pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN), one of the cofilin-mediated F-actin regulators, in the CSEN binding to Kv4.2 or GluN1 (an NMDAR subunit). PLPP/CIN dephosphorylated CSEN in competition with casein kinase 1, independent of cofilin dephosphorylation. As compared to wild-type mice, PLPP/CIN transgenic (PLPP/CINTg) mice showed the enhancement of Kv4.2–CSEN binding, but the reduction in CSEN–GluN1 binding. In addition, PLPP/CINTg mice exhibited the higher intensity (severity), duration and progression of seizures, but the longer latency of seizure on-set in response to kainic acid. PLPP/CIN knockout mice reversed these phenomena. Therefore, we suggest that PLPP/CIN-mediated CSEN dephosphorylation may play an important role in the functional coupling of NMDAR and Kv4.2, which regulates the neuronal excitability.

Action of adrenal and gonadal steroid hormones on kainic acid-evoked seizures in a rat model of epileptogenesis

ABSTRACTEpilepsy is one of most reported neurological disorders after migraine, stroke and Alzheimer's disease. Empiric clinical data reveal that seizures and epilepsy more likely affect men than women. The aim of present study was to investigate the effect of steroid adrenal and gonadal hormones on the intensity, dynamics and latency of kainic acid-evoked seizure and lethality in a rat model of epileptogenesis. After surgical adrenalectomy/gonadectomy, male rats were at random assorted in groups and treated from postoperative day 1 to day 5 with corticosterone (30 mg/kg), estradiol (0.03 mg/kg), progesterone (75 mg/kg), dihydroprogesterone (75 mg/kg) and dihydrotestosterone (0.75 mg/kg). Spontaneous recurrent seizures generated by kainic acid were assessed. The treatment with corticosterone eliminated the aggravation of kainic acid-evoked seizures produced by adrenalectomy/gonadectomy. The application of corticosterone decreased the seizure intensity by 31% and prevented seizure-associated animal death. The effect of estradiol treatment was quite opposite. Estradiol treatment exacerbated the somatic and behavioural aspects of kainic acid-evoked epilepsy-like syndrome. The hormone increased the intensity of kainic acid-evoked seizures by 31%, decreased the latency of clonic weak seizures by 49% and enhanced the associated lethality by 133%. The treatment with progesterone or dihydroprogesterone produced minor alterations in intensity and latency of kainic acid-evoked seizures in the operated male rats. The application of dihydrotestosterone significantly aggravated the kainic acid-evoked seizures. In summary, hormonal unbalance could play an important role for seizure susceptibility in epileptogenesis. Corticosterone has better anti-seizure activity than progesterone and testosterone has significant pro-convulsive activity.

FV 7 High-frequency anterior thalamus stimulation increases alertness in epilepsy patients during alert- and drowsy-wakefulness

Objective Deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) reduces frequency and intensity of epileptic partial and secondarily-generalized seizures. ANT-DBS disrupts sleep in epilepsy patients. We investigated the impact of ANT-DBS on alertness in wakeful epilepsy patients. This might help to better understand mechanisms of action of high frequency ANT-DBS in humans. Methods Four patients with different structural epileptic pathology were included in this retrospective case-cohort study. We analysed physiological parameters of alertness during stimulation-ON and -OFF intervals in short- and long-term electroencephalograms (EEG) of patients in states of alert- and drowsy-wakefulness. Results We demonstrate that ANT-DBS increases acutely and reproducible the alertness of wakeful patients during stimulation-ON intervals. Significance This is the first demonstration of such an effect in humans. The enhanced alertness might contribute to the antiepileptic effect of ANT-DBS. Corroborated with the sleep-disruption effect of ANT-DBS in epilepsy patients, our results deliver circumstantial evidences that high-frequency ANT-DBS activates thalamo-cortical connections that promote wakefulness. In addition, our data suggest that ANT-DBS might improve the post-ictal recovery of epileptic patients and counterbalance the antiepileptic-drug induced fatigue.

Circadian variation in anticonvulsant activity of valproic acid in mice

PurposeThis study aims to investigate whether valproic acid (VPA) anticonvulsant activity varied according to circadian dosing-time in mice. MethodsVPA was administered to mice at four circadian stages (1, 7, 13 and 19h after light onset, (HALO)). The controls received a saline injection followed by a s.c. injection of pentylenetetrazol (PTZ) 30min later. In pretreated animals, VPA was administered 30min before PTZ administration. ResultsThe results obtained showed that VPA-induced anticonvulsant activity depends on circadian dosing-time in mice. VPA has significantly increased the latency of the first clonic seizure at all circadian stages. This increase varied depending on the time of VPA pre-treatment, the highest and the lowest increases were recorded respectively at 7 and 19 HALO. The Cosinor analysis has also validated a circadian rhythm of this increase. The intensity of seizures in pretreated mice varied significantly according to circadian stage. The highest seizure intensity was recorded at 19 HALO. A circadian rhythm of the seizure intensity in VPA pretreated mice was detected, with an acrophase located at the middle of the dark span (Ø=18.09 HALO±2.27h). ConclusionThe present findings provide evidence for a pronounced anticonvulsant effect of VPA when administered in the 2nd middle of the light-rest span in mice. These results might probably be due to the circadian variation of VPA pharmacokinetic since our previous studies showed that the optimal tolerance corresponded to the middle of the rest span, the time which induces the highest total plasma clearance.

O18 Cathodal transcranial direct current stimulation reduces seizure frequency and modulates brain functional connectivity with drug-resistant temporal lobe epilepsy: A sham controlled study

Purpose One-third of epilepsy patients develop drug resistance epilepsy (DRE), and half of them can benefit from the surgical removal of epileptic focus (EF). Neuromodulation represents the only hope to ameliorate the quality of life of the remaining patients. Cathodal transcranial direct current stimulation (ctDCS) is a techniques able to non-invasively inhibit cortical excitability, which is abnormally increased in epilepsy, but its efficacy in reducing seizures and in modulating epileptic network is still under debate. We evaluated the efficacy of 20-min 1 mA ctDCS vs sham-tDCS in reducing seizure frequency and in modulating the functional connectivity (FC) between EF and the other cortical areas, in temporal DRE patients. Methods After 7 days of seizure diary, patients were randomized to either first-ctDCS or first-sham-ctDCS treatment. On day 8, patients underwent the assigned stimulation. On day 38, patients underwent the single-session opposite stimulation. 7 days after the second session, the study was concluded. The ctDCS cathode was placed over the EF and the anode over the contralateral homologous region. Immediately before and after stimulations, a one-hour resting state closed-eyes 19-electrodes video-EEG recording was acquired. We enrolled ten patients affected by temporal lobe DRE (4 males; 42 ± 15.7 years old; 4 symptomatic and 6 cryptogenic;5 right EF). Results ctDCS reduced the percent weekly SF more than sham stimulation (−71 ± 33% ctDCS vs 25 ± 125% sham; Z = −2.201, p = 0.028). EA changes did not differ between ctDCS respect to sham-ctDCS ( p > 0.200 consistently). No patients reported worsening of SF or of seizure intensity. FC changed after real stimulation in all patients and involved the focus in 71% of the new connections. No FC change was found after sham. Conclusions we demonstrated that an individualized ctDCS reduced seizure frequency in temporal DRE without any safety concern. FC changes may help to explain ctDCS effects on DRE patients.

Susceptibility to Soman Toxicity and Efficacy of LY293558 Against Soman-Induced Seizures and Neuropathology in 10-Month-Old Male Rats.

Acute nerve agent exposure causes prolonged status epilepticus (SE), leading to death or long-term brain damage. We have previously demonstrated that LY293558, an AMPA/GluK1 kainate receptor antagonist, terminates SE induced by the nerve agent soman and protects from long-term brain damage, in immature rats and young-adult rats, even if administered with a relatively long latency from the time of exposure. However, susceptibility to the lethal consequences of SE increases with age, and mortality by SE induced by soman is substantially greater in older animals. Therefore, in the present study, we compared the susceptibility to soman toxicity of 10-month-old male rats with that of young-adult male rats (42 to 50days old) and examined the protective efficacy of LY293558 in the older group. A lower percentage of the 10-month-old rats developed SE after injection of 1.2×LD50 soman, compared to the young adults, the latency to seizure onset was longer in the older rats, and seizure intensity did not differ between the two age groups. However, mortality rate in the older rats who developed SE was higher than in the young adults. Acetylcholinesterase activity in the amygdala, hippocampus, and piriform cortex did not differ between the two age groups. Administration of LY293558 at 20 or 60min post-exposure suppressed SE, increased 24-h survival rate, decreased the long-term risk of death, reduced neuronal degeneration in the amygdala, hippocampus, piriform, and entorhinal cortices, and facilitated recovery from body weight loss. Thus, LY293558 is an effective countermeasure against soman toxicity also in older animals.

Prenatal stress potentiates febrile seizure and leads to long-lasting increase in cortisol blood levels in children under 2years old.

Neurological disorders can be exacerbated in an offspring that is exposed to stress prenatally. This study is aimed to investigate the severity of febrile seizures (FS) in the offspring under 2years old that were prenatally stressed. In this study, 158 children below 2years old with FS were selected. Information about convulsion including seizure lasting, recurrence of seizure, age of the first seizure and type of FS was gathered. Blood samples were obtained from the offspring to measure the cortisol blood levels. Questionnaire was filled in to evaluate the perceived stress and exposure or non-exposure to major stresses during pregnancy. Results of this study showed that both high Perceived Stress Scores (PSS) during pregnancy and exposure to major stresses during pregnancy significantly increased seizure duration and seizure intensity. Also, the appearance of complex FS was significantly higher in prenatally stressed children than the unexposed ones. Further, cortisol blood levels were significantly higher in prenatally stressed subjects. It can be concluded that both higher PSS and/or exposure to major stresses during pregnancy potentiate FS parameters and lead to long lasting increase in cortisol blood levels in the offspring.

Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation

In this paper the influence of two different ketogenic diets (KDs) on the seizure-evoked elemental anomalies of hippocampal formation was examined. To achieve this purpose normal and pilocarpine treated rats previously fed with one of the two high fat and carbohydrate restricted diets were compared with animals on standard laboratory diet. The ketogenic ratios of the examined KDs were equal to 5:1 (KD1) and 9:1 (KD2).KD1 and standard diet fed animals presented similar patterns of seizure-evoked elemental changes in hippocampal formation. Also the analysis of behavioral data recorded after pilocarpine injection did not show any significant differences in intensity and duration of seizures between KD1 and standard diet fed animals.Higher ketogenic ratio KD2 introduced in the normal hippocampal formation prolonged changes in the accumulation of P, K, Zn and Ca. Despite this, both the intensity and duration of seizures were significantly reduced in rats fed with KD2 which suggests that its saving action on the nerve tissue may protect brain from seizure propagation. Also seizure-evoked elemental anomalies in KD2 animals were different than those observed for rats both on KD1 and standard diets. The comparison of seizure experiencing and normal rats on KD2, did not show any statistically significant differences in elemental composition of CA1 and H hippocampal areas whilst in CA3 area only Zn level changed as a result of seizures. DG was the area mostly affected by seizures in KD2 fed rats but areal densities of all examined elements increased in this hippocampal region.

Predicting success of vagus nerve stimulation (VNS) from EEG symmetry

PurposeVagus nerve stimulation (VNS) has shown to be an effective treatment for drug resistant epilepsy, with achieving more than 50% seizure reduction in one third of the treated patients. In order to predict which patients will profit from VNS, we previously found that a low pairwise derived Brain Symmetry Index (pdBSI) could potentially predict good responders to VNS treatment. These findings however have to be validated before they can be generalized. Methods39 patients (age 18–68 years) with medically intractable epilepsy who were referred for an implanted VNS system were included. Routine EEG registrations, recorded before implantation, were analyzed. Artefact-free epochs with eyes open and eyes closed were quantitatively analyzed. The pdBSI was tested for relation with VNS outcome one year after surgery. ResultsTwenty-three patients (59%) obtained a reduction in seizure frequency, of whom ten (26%) had a reduction of at least 50% (good responders) and thirteen (33%) a reduction of less than 50% (moderate responders). Sixteen patients without seizure reduction are defined as non-responders. No significant differences were found in the pdBSI of good responders (mean 0.27), moderate responders (mean 0.26) and non-responders (mean 0.25) (p>0.05). Besides seizure reduction, many patients (56%) reported additional positive effects of VNS in terms of seizure duration, seizure intensity and/or postictal recovery. ConclusionEEG features that correlate with VNS therapy outcome may enable better patient selection and prevent unnecessary VNS surgery. Contrary to earlier findings, this validation study suggests that pdBSI might not be helpful to predict VNS therapy outcome.

POSSIBILITIES TO USE A FIXED COMBINATION OF PIRACETAM AND CINNARIZINE IN NEUROLOGICAL PRACTICE

The article discusses the possibility of using the complex drug Phezam, containing 400 mg of Piracetam and 25 mg of Cinnarizine in neurological practice. The advantage of a combination of nootropic and vasoactive substances is due to a balanced and diversified influence on the different links of pathogenesis diseases. Piracetam targets the turnover of cell membranes, neurotransmission, has a neuroprotective effect, influences the neuroplasticity, the energy exchange in the cage and the vascular mechanisms (blood cells, cardiovascular wall and coagulation). The second component of the drug Cinnarizine has vasodilatating properties, suppresses the activity of the labyrinth and improves flow blood properties. When discussing the drug-induced parkinsonism, the opposite effects of the drug components on the dopaminergic system are described. The Phezam has shown its efficacy in the preventive treatment of migraines (reducing of frequency and intensity of seizures). In patients with chronic brain ischemia Phezam improved a neurological status, cognitive functions, blood flow indicators, and quality of life. The positive effects of Phezam during the recovery period of ischaemic stroke with speech and moderate cognitive disorders are reported. The characteristics of the metering regime are the possibility to use low-and high-dosage therapy. The drug showed good tolerability and economic advantages over the use of active substances separately.

The Effect of Quercetin on Pro- and Anti-Inflammatory Cytokines in a Prenatally Stressed Rat Model of Febrile Seizures.

Febrile seizures are childhood convulsions resulting from an infection that leads to an inflammatory response and subsequent convulsions. Prenatal stress has been shown to heighten the progression and intensity of febrile seizures. Current medications are costly and have adverse effects associated with prolonged use. Quercetin flavonoid exhibits anti-inflammatory, anti-convulsant, and anti-stress effects. This study was aimed to investigate the therapeutic effect of quercetin in a prenatally stressed rat model of febrile seizures. We hypothesized that quercetin will alleviate the effects of prenatal stress in a febrile seizure rat model. On gestational day 13, Sprague-Dawley rat dams were subjected to restraint stress for 1 hour/d for 7 days. Febrile seizures were induced on postnatal day 14 on rat pups by intraperitoneally injecting lipopolysaccharide followed by kainic acid and quercetin on seizure onset. Hippocampal tissue was harvested to profile cytokine concentrations. Our results show that quercetin suppresses prenatal stress–induced pro-inflammatory marker (interleukin 1 beta) levels, subsequently attenuating febrile seizures. This shows that quercetin can be therapeutic for febrile seizures in prenatally stressed individuals.

Exploratory behavior alteration as an epileptic comorbidity in elevated plus maze test

Introduction: Epileptic seizure consists of preictal, ictal and postictal period. Postictal period is characterized by a variety of psychiatric phenomenon of which the most frequent ones are anxiety and depressive disorder. Anxiety in rodents can be assessed by measuring the exploratory behavior. Lindane evokes generalized tonic-clonic epileptic seizures in rats, when applied intraperitoneally, due to its lypophilic characteristics. Aim: The aim of this study was to assess exploratory behavior linked with anxiety level in the elevated plus maze test (EPM) upon generalized seizures, induced by lindane in male rats. Material and methods: The experiment was conducted on Wistar albino male rats that were randomly divided into: control group (DMSO, 0.5 ml/kg) and experimental group (lindane, 8 mg/kg) (n=8, each). After the drug injection, the assessment of the seizure intensity lasted for 30 minutes. Descriptive rating scale was used to describe the seizure severity. Subsequently, the EPM testing took place immediately after evoking the seizure (Test 1), after 1h (Test 2) and after 24h (Test 3). Time spent in open areas and number of transitions was further analyzed. Results: Experimental group of animals spent less time in open areas of EPM, when compared to controls in Test 1 and Test 2. The same holds true for the number of transitions to the open area, i.e. lindane-treated animals tend to stay in enclosed parts of the maze in Test1, Test 2. Finally, in Test 3 there was no significant difference between the groups, in any parameter of interest. Conclusion: Lindane-induced generalized epileptic seizures are accompanied by reduced exploratory behavior in the elevated plus maze test, up to 24h after the seizure ended. This finding can be a basis for the further translational research of anxiety as epileptic comorbidity in this experimental model of epilepsy.

A two-year retrospective evaluation of perampanel in patients with highly drug-resistant epilepsy and cognitive impairment

The objective of this work was to review systematically the efficacy and tolerability of perampanel (PER) in residential patients of an epilepsy center. We adopted an industry-independent noninterventional retrospective evaluation on the basis of the paper and electronic records complemented by personal information on the part of the treating neurologists. All patients (N=26, 15 females, mean age: 30, range 21-55years) started on PER from its introduction to the market in September 2012 until December 15th 2013 were included. Evaluation was carried out after 6, 12, and 24months of PER treatment. Changes in seizure frequency were calculated as the number of seizures during three months on PER compared to a three-month baseline period. The Clinical Global Impression Scale served as an instrument to record changes in seizure intensity beyond numerical values. Adverse effects were documented by means of the Liverpool Adverse Events Profile. Most patients had structural or metabolic epilepsy, 2 patients suffered from Lennox-Gastaut syndrome, 2 from other symptomatic generalized epilepsy. All patients had grade III drug-resistant epilepsy. All patients had additional cognitive deficits of different degree. The retention rates were 61.5% after 6months, 46.2% after 12months, and 42.3% after 24months. The responder rates were 11.5% after 6months, 23.1% after 12months, and 7.7% after 24months. Partial responders (positive CGI and/or seizure reduction <50%) included, the respective values were 26.9%, 38.5%, and 23.1%. Only 1 patient was seizure free at 12months (but not at 24months). A loss of efficacy in the second year of treatment was suspected but the decrease of the responder rate could also be ascribed to a number of different circumstances. Adverse effects in the psychiatric field like irritability, aggression, increased sensitivity, and suicidal ideation/behavior occurred in 50% of the patients. They were the main reason to discontinue PER. After one year of treatment PER showed reasonable efficacy in a particularly difficult-to-treat population. Psychiatric adverse effects forced discontinuation in many cases.

Antiepileptic potential of &lt;i&gt;Silybum marianum&lt;/i&gt; seeds in pentylenetetrazol-induced kindled mice

&lt;p class="Abstract"&gt;Epilepsy is an abnormality of nervous system showing seizures. Despite, the known antiepileptic activity of plants possessing anti-oxidant properties, &lt;em&gt;Silybum marianum&lt;/em&gt; has not been studied yet. Therefore, present experiment was planned to evaluate antiepileptic potential of &lt;em&gt;S. marianum&lt;/em&gt; (100, 200 and 300 mg/kg) seeds ethanol extract in pentylenetetrazol-induced kindled mice (n = 30). &lt;em&gt;S. marianum&lt;/em&gt; seed extract (300 mg/kg) provided significant protection against pentylenetetrazol-induced convulsions (seizure intensity, latency and lethality) comparable with reference drug (valproic acid). Furthermore, 300 mg/kg/day dose was effective to prevent oxidative stress causing significant decrease in the lipid peroxidation (1.4 ± 0.4 nmol/mg protein) and increased superoxide dismutase (0.4 ± 0.1 μmol/mg protein) and catalase activity (4.7 ± 0.8 U/mL) of mice brain as compared to induced untreated group (p&amp;lt;0.05). It was concluded that antiepileptic activity of &lt;em&gt;S. marianum&lt;/em&gt; seeds was due to its anti-oxidant property.&lt;/p&gt;&lt;p class="Abstract"&gt;&lt;strong&gt;Video Clip&lt;/strong&gt;&lt;/p&gt;&lt;p class="Abstract"&gt;&lt;a href="https://www.youtube.com/v/NAh_04UzpYM"&gt;Experimental induction of seizures:&lt;/a&gt; 10 min 4 sec&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice.

The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amygdala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV). During amygdala kindling, behavioral changes (from stage 0 to stage 5) of mice were accompanied by after-discharges (ADs) of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. During seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with seizure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchronization were different.

Physical training decreases susceptibility to pilocarpine-induced seizures in the injured rat brain

There is growing evidence that physical activity ameliorates the course of epilepsy in animal models as well as in clinical conditions. Since traumatic brain injury is one of the strongest determinants of epileptogenesis, the present study focuses on the question whether a moderate long-term physical training can decrease susceptibility to seizures evoked following brain damage. Wistar rats received a mechanical brain injury and were subjected to daily running sessions on a treadmill for 21 days. Thereafter, seizures were induced by pilocarpine injections in trained and non-trained, control groups. During the acute period of status epilepticus, the intensity of seizures was assessed within the six-hour observation period. The trained rats showed considerable amelioration of pilocarpine-induced motor symptoms when compared with their non-trained counterparts. Histological investigations of effects of the brain injury and of physical training detected significant quantitative changes in parvalbumin-, calretinin- and NPY-immunopositive neuronal populations. Some of the injury-induced changes, especially those shoved by parvalbumin-immunopositive neurons, were abolished by the subsequent physical training procedure and could, therefore, be considered as neuronal correlates of the observed functional amelioration of the injured brain.

Global assessment of the severity of epilepsy (GASE) Scale in children: Validity, reliability, responsiveness.

The Global Assessment of Severity of Epilepsy (GASE) Scale is a single-item, 7-point global rating scale designed for neurologist-report of overall severity of epilepsy in children. Building on previous preliminary evidence of its validity and reliability for research and clinical use, this study evaluated the GASE Scale's construct validity, reliability, and responsiveness to changes in severity of epilepsy. Data used for the study arose from the Health-Related Quality of Life in Children with Epilepsy Study (HERQULES), a 2-year multicenter prospective cohort study (n = 374) with observations taken at baseline, and 6, 12, and 24 months after diagnosis. Construct validity and reliability were quantified using Spearman's correlation and intraclass correlation coefficient (ICC). Responsiveness was assessed using both distribution-based and anchor-based indices. The GASE Scale was at least moderately correlated (r ≥ 0.30) with several key clinical aspects and most strongly correlated with frequency and intensity of seizures and interference of epilepsy or drugs with daily activities (r > 0.30). Total variation in GASE Scale scores explained by seven core clinical aspects of epilepsy increased over time (R(2) = 28% at baseline to R(2) = 70% at 24 months). The GASE Scale had modest test-retest reliability (ICC range: 0.52-0.64) and was responsive to changes in clinical criteria (standardized response mean range: 0.49-0.68; probability of change range: 0.69-0.75; Guyatt's responsiveness statistic range: 0.56-0.84). The GASE Scale showed potential to discriminate "stable" and "changed" patients according to select criteria and to a composite score (area under the receiver operating characteristic [ROC] curve range: 0.50-0.67). Results offer additional evidence in support of the GASE Scale's validity, reliability, as well as responsiveness to changes in severity of epilepsy in children. We conclude that the GASE Scale is a potentially useful tool for assessing the severity of epilepsy in both clinical and research settings.

Pilocarpine-induced status epilepticus in mice: A comparison of spectral analysis of electroencephalogram and behavioral grading using the Racine scale

Pilocarpine-induced status epilepticus (SE) is a widely used seizure model in mice, and the Racine scale has been used to index seizure intensity. The goal of this study was to analyze electroencephalogram (EEG) quantitatively using fast Fourier transformation (FFT) and statistically evaluate the correlation of electrographic seizures with convulsive behaviors. Simultaneous EEG and video recordings in male mice in a mixed genetic background were conducted and pilocarpine was administered intraperitoneally to induce seizures. The videos were graded using the Racine scale and the root-mean-square (RMS) power analysis of EEG was performed with Sirenia Seizure Pro software. We found that the RMS power was very weakly correlated with convulsive behavior induced by pilocarpine. Convulsive behaviors appeared long before electrographic seizures and showed a strong negative correlation with theta frequency activity and a moderate positive correlation with gamma frequency activity. Racine scores showed moderate correlations with RMS power across multiple frequency bands during the transition from first electrographic seizure to SE. However, there was no correlation between Racine scores and RMS power during the SE phase except a weak correlation with RMS power in the theta frequency. Our analysis reveals limitations of the Racine scale as a primary index of seizure intensity in status epilepticus, and demonstrates a need for quantitative analysis of EEG for an accurate assessment of seizure onset and severity.