Time Of Seizure Onset Research Articles

Variances of quantifying of Virchow–Robin spaces detecting the different functional status of glymphatic system in simple febrile seizures affected by seizures duration

The Virchow-Robin spaces (VRs) in the cerebral glymphatic system play a vital role in waste clearance from the brain. Simple febrile seizures (SFS) are a common type of seizures marked by an inappropriate fluid exchange. The mechanism of evident differences in glymphatic function among SFS with varying seizure duration is unknown. Therefore, the goal of this study was to see whether there were any variations in glymphatic function among SFS based on seizures duration. We retrospectively studied 30 children with SFS lasting more than 5 minutes (SFS > 5M), 40 children with SFS lasting 5 minutes or less (SFS ≤ 5M), and 35 healthy controls aged 6 to 60 months who underwent magnetic resonance imaging (MRI). A custom-designed automated method that used T2-weighted imaging (T2WI) to segment the visible VRs. The VRs metrics were measured and compared studied groups. The VRs metrics, seizure duration the time gap between seizure onset and MRI scan were studied as well. VRs counts were lower (P < .001) in the SFS ≤ 5M (445.80 ± 66.10) and the control (430.77 ± 182.55) groups in comparison to SFS > 5M (642.70 ± 100.62). Similar results were found for VRs volume (VRsvol_SFS > 5M, 8514.63 ± 835.33mm3, VRsvol_SFS ≤ 5M, 6390.43 ± 692.74 mm3, VRsvol_control, 6048.37 ± 111.50 mm3; P < .001). However, in the SFS ≤ 5M, VRs measurements were lower than in the SFS > 5M (P < .001). VRs measurements were positively connected with seizure duration and inversely correlated with the course following seizure onset and MRI scan time in both SFS groups. SFS are positively correlated to glymphatic dysfunction since they cause enlarged VRs; additionally, VRs can be used as a biomarker in SFS > 5M and contribute to the mechanism.

Nucleus accumbens shell modulates seizure propagation in a mouse temporal lobe epilepsy model.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures which in some conditions can develop into secondarily generalized tonic-clonic seizures by the propagation of epileptic activities in the temporal lobe to other brain areas. The nucleus accumbens (NAc) has been suggested as a treatment target for TLE as accumulating evidence indicates that the NAc, especially its shell, participates in the process of epileptic seizures of patients and animal models with TLE. The majority of neurons in the NAc are GABAergic medium spiny neurons (MSNs) expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). However, the direct evidence of the NAc shell participating in the propagation of TLE seizures is missing, and its cell type-specific modulatory roles in TLE seizures are unknown. In this study, we microinjected kainic acid into basolateral amygdala (BLA) to make a mouse model of TLE with initial focal seizures and secondarily generalized seizures (SGSs). We found that TLE seizures caused robust c-fos expression in the NAc shell and increased neuronal excitability of D1R-expressing MSN (D1R-MSN) and D2R-expressing MSN (D2R-MSN). Pharmacological inhibition of the NAc shell alleviated TLE seizures by reducing the number of SGSs and seizure stages. Cell-type-specific chemogenetic inhibition of either D1R-MSN or D2R-MSN showed similar effects with pharmacological inhibition of the NAc shell. Both pharmacological and cell-type-specific chemogenetic inhibition of the NAc shell did not alter the onset time of focal seizures. Collectively, these findings indicate that the NAc shell and its D1R-MSN or D2R-MSN mainly participate in the propagation and generalization of the TLE seizures.

Anticonvulsant and Anti-anxiety Effects of Royal Jelly in Adult Male Syrian Rats

Objective Royal jelly is a honey bee secretion with beneficial effects on the nervous system. The present study aims to investigate the effects of royal jelly in reducing seizure and anxiety-like behaviors in Syrian rats. Methods This is an experimental study. In the seizure model, 25 male white Syrian rats were randomly divided into five groups: Control, royal jelly 100 mg/kg, royal jelly 200 mg/kg, royal jelly 400 mg/kg, and phenobarbital. After 30 minutes, strychnine was injected to induce seizure in animals. The time of seizure onset, seizure duration, and mortality rate in animals were recorded. In the anxiety model, 35 male white Syrian rats were randomly divided into five groups: Control, royal jelly 50 mg/kg, royal jelly 100 mg/kg, royal jelly 200 mg/kg, and diazepam. Anxiety-like behaviors were examined by using the elevated plus maze (EPM) test. Data analysis was performed using one-way ANOVA, and P&lt;0.05 was statistically significant. Results Royal jelly at doses of 200 and 400 mg/kg delayed the time of seizure onset and reduced the seizure duration compared to the control group (P&lt;0.05). The mortality rate was also reduced after using different doses of royal jelly compared to the control group (P&lt;0.05). Moreover, royal jelly at doses of 50 and 100 mg/kg increased the time spent in the open arms of the EPM platform and the number of entries to the open arms compared to the control group (P&lt;0.05). Conclusion Administration of royal jelly can reduce strychnine-induced seizure and modulate anxiety-like behaviors in rats.

Effects of Satureja Bachtiarica Essential Oil in Preventing Seizure in Pentylenetetrazol-Kindled Mice.

Epilepsy is a group of chronic neurological disorders characterized by seizures. The present study aimed to investigate the effects of Satureja bachtiarica essential oil in preventing epilepsy. In this experimental study, 50 mice were randomly assigned to five groups of 10 each. The control group received normal saline plus tween-80 and after 30 min pentylenetetrazol (PTZ). Groups 2 and 3 were treated first with S. bachtiarica essential oil at 50 and 100 mg/kg, respectively and then after 30 min received PTZ. Group 4 received diazepam and 30 min later PTZ. Group 5 received flumazenil and 30 min later PTZ. After the last injection of PTZ, the time of seizure onset, seizure severity and score, the completion time of each seizure (attack episode), and mortality rate in different groups were recorded and compared. The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to PTZ-treated mice caused a significant increase in latency to the first seizure and survival of mice, as well as a significant decrease in the frequency of the head and upper limbs seizure, total body seizures, tonic seizures, and jumping. S. bachtiarica essential oil at 100 mg/kg caused a significant decrease in the head tic frequency. The administration of flumazenil significantly inhibited S. bachtiarica essential oil-induced effects and increased the head and upper limbs seizures, tonic seizures, and jumping. The present study demonstrated that S. bachtiarica essential oil could prevent PTZ-induced seizure and these findings authenticate the traditional claims about the use of S. bachtiarica in treating epilepsy. The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to pentylenetetrazol PTZ-treated mice caused a significant increase in latency to the first seizure.• The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to PTZ-treated mice caused a significant decrease in the frequency of the head and upper limbs seizures, total body seizures, tonic seizures, and spin and jump.• The administration of flumazenil significantly inhibited S. bachtiarica essential oil-induced effects and increased the head and upper limbs seizures, tonic seizures, and jumping. Epilepsy is one of the most common disorders of the central nervous system, so that one in every 100 people is suffering from epilepsy globally. Despite the development of antiepileptic drugs, novel strategies are sought out because of drug resistance and the side effects resulting from these drugs at high concentrations. Researchers have focused on plants for certain reasons such as availability, the history of long-term use, being nature-based, and relative safety. In the current study, the effect of the pretreatment with S. bachtiarica essential oil in preventing seizure was studied in the pentylenetetrazol-kindled mice. The injection of 50 and 100 mg/kg of S. bachtiarica essential oil caused a significant increase in latency to the first seizure and survival duration, and a significant decrease in the frequency of the head and upper limbs seizures, tonic seizures, and spin and jump in the pentylenetetrazol-receiving mice.

Subtotal hemispherotomy for intractable lesional hemispheric epilepsy without hemiparesis in children

PurposeWe analyzed the surgical indications, outcomes, and prognostic factors of subtotal hemispherotomy for intractable lesional hemispheric epilepsy in children with almost normal motor function and summarized its surgical strategies. MethodsWe retrospectively analyzed 20 children who underwent subtotal hemispherotomy (hemispheric disconnection sparing sensorimotor cortex) between March 2015 and May 2021. The children were divided into seizure-free group and residual seizures group according to their surgical outcomes. The surgical outcome was based on International League Against Epilepsy (ILAE) classification (class 1–6). All presurgical evaluation data were collected and analyzed. ResultsAmong the 20 children, the mean age at the time of seizure onset, mean age at the time of surgery, and mean follow-up time was 3.2 ± 2.8, 7.5 ± 4.4, and 3.5 ± 2.1 years, respectively. All children had hemispheric lesion on MRI. At the last follow-up evaluation, 75% (15/20) of children remained seizure-free. Univariate analyses revealed that the electrocorticogram finding of epileptiform discharges in the central cortex after disconnection were poor prognostic factors for seizure outcomes (P < 0.05). Disconnection of the central operculum and insula was a poor prognostic factor for motor function after surgery (P < 0.05). ConclusionsFor intractable lesional hemispheric epilepsy with no hemiparesis, subtotal hemispherotomy can be performed with favorable seizure outcome. Disconnection of the central operculum and insula may increase the possibility of motor function injury.

Revisiting an ancient legend: influence of the lunar cycle on occurrence of first-ever unprovoked seizures.

The mythical effect of the lunar cycle on seizures has been debated over time. Previously healthy individuals presenting with first-ever seizures in whom investigations are negative often invoke questions about potential reasons including a full moon. To determine whether there is a temporal relationship between the occurrence of the first-ever unprovoked seizure and the lunar cycle. We studied adults who presented with a first-ever unprovoked seizure to two tertiary centres in Australia. Seizure onset time was obtained from the emergency department and ambulance documentations. We used Poisson regression modelling and incidence rate ratios (IRR) to determine whether seizures have a preponderance for a particular lunar phase. We performed further analysis on 'first seizure epilepsy' and 'first seizure not epilepsy' subgroups based on the International League Against Epilepsy criteria for a diagnosis of epilepsy after a single unprovoked seizure. We analysed 1710 patients (38% females; median age 39 years), of whom 18% had epileptiform abnormalities on electroencephalogram (EEG) and potentially epileptogenic lesions were detected on neuroimaging in 28%. Based on the EEG and imaging findings, 684 (40%) patients were categorised as 'first seizure epilepsy' and 1026 (60%) 'first seizure not epilepsy'. The whole cohort and subgroup analysis demonstrated no significant difference in the seizure occurrence among the four lunar quarters. First unprovoked seizures are not influenced by the lunar cycle. Patients pondering the cause of their first-ever unprovoked seizure can be reassured that the full moon was not responsible.

Brain Malformations in C57BL/6 Mice Affect Seizure Onset

BackgroundBrain malformations are known to cause cognitive delay and seizures in both humans and mice. It has been demonstrated that the neocortex and cerebellum of the brain are vulnerable to malformations affecting neuronal lamination and synaptic connectivity. Our objective was to determine if the presence of sporadic neocortical and/or cerebellar brain malformation affected time to seizure onset in a large cohort of C57BL/6 mice, as this strain is widely used in neuroscience and epilepsy research. We hypothesized that the presence of cerebellar and/or neocortical malformations in mice would reduce seizure onset in both male and female mice.MethodsFlurothyl was used to induce seizures in C57BL/6J mice, and the time to seizure onset was recorded. Following seizures, mice were euthanized and brains were placed in 4% paraformaldehyde and then into 30% sucrose. Brains underwent cryosectioning at 45um thickness, with every other coronal forebrain section and 15 cerebellum sagittal sections mounted on gelatin‐coated slides. After Nissl staining, high and low power brightfield microscopy were used to screen the stained slides for presence of cerebellar and neocortical malformations. Only malformations present in 2 or more sections in the neocortex or cerebellum were classified as a malformation. Statistical analysis was performed using two‐tailed independent t‐tests with significance at p &lt; 0.05.ResultsOut of 132 mouse brains, 82 (62.1%) had either neocortical and/or cerebellar malformations and 49 (37.71%) had no malformations. Of 62 female mice, 40 (64.5%) had malformations, and 22 (35.48%) did not have malformations. Of 69 male mice, 42 (67.74%) had malformations, and 27 (43.54%) did not have malformations. In the female malformations group, 7 of 40 (17.5%) were exclusively neocortical, 26 of 40 (65%) were cerebellar, and 7 of 40 (17.5%) had both neocortical and cerebellar malformations. Statistically significant differences in seizure onset were found in the female cohort between those with malformations and without malformations (p = 0.016). Comparison of female mice with both cerebellar and neocortical malformations to female mice with no malformations also demonstrated statistically significant differences (p = 0.017). For the male malformations cohort, 7 of 42 (16.67%) were neocortical, 31 of 42 were cerebellar, and 4 of 42 (9.52%) had both neocortical and cerebellar malformations. Comparison of male mice with only neocortical malformations to those with no malformations yielded significant results (p = 0.04). Differences in time to seizure onset were also found when comparing male mice with only cerebellar malformations to those with only neocortical malformations (p = 0.016).ConclusionsSignificant differences in seizure onset time were present in both genders of C57BL/6 mice with either cerebellar and/or neocortical malformations. This raises important questions regarding pre‐existing malformations in mice used to study diseases such as epilepsy. For example, sporadic malformations influencing seizure onset could affect the efficacy of anti‐seizure medications being researched.

Channa Striatus Protects Against PTZ-Induced Seizures in LPS Pre-conditioned Zebrafish Model.

Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Mounting evidence suggests the link between epileptogenesis and neuroinflammation. We hypothesize that eliminating neuroinflammation can alleviate seizure severity and prolong seizure onset. Channa striatus (CS) is a snakehead murrel commonly consumed by locals in Malaysia, believed to promote wound healing and mitigate inflammation. This study aims to unravel the anticonvulsive potential of CS extract on neuroinflammation-induced seizures using an adult zebrafish model. Neuroinflammation was induced via cerebroventricular microinjection of lipopolysaccharides from E. coli and later challenged with a second-hit pentylenetetrazol at a subconvulsive dose of 80 mg/kg. Zebrafish behaviour and swimming pattern analysis, as well as gene expression analysis, were done to study the pharmacological property of CS. CS extract pre-treatment in all doses significantly reduced seizure score, prolonged seizure onset time and slightly improved the locomotor swimming pattern of the zebrafish. CS extract pre-treatment at all doses significantly reduced the expression of NFKB gene in the brain, and CS extract at 25 mg/L significantly reduced the IL-1 gene expression suggesting anti-neuroinflammatory properties. However, there were no significant changes in the TNFα. Besides, CS extract at 50 mg/L also elevated the expression of the CREB gene, which exerts neuroprotective effects on the neurons and the NPY gene, which plays a role in modulating the inhibition of the excitatory neurotransmission. To sum up, CS extract demonstrated some anticonvulsive and anti-inflammatory activity on neuroinflammation-induced seizures. Still, more studies need to be done to elucidate the mechanism of action of CS extract.

Evaluation of the anticonvulsant effect of carvacrol in Pentylenetetrazole (PTZ)-induced seizures in male mice: N-Methyl-D-Aspartic Acid receptor role

Background. Epilepsy is one of the most common neurological disorders after stroke. Due to the side effects and poor response of conventional anticonvulsant drugs, researchers have turned their attention to find new drugs. Carvacrol is a phenolic compound with neuroprotective, anti-inflammatory, antioxidant and anticonvulsant effects. The aim of the study was to investigate the anticonvulsant effects of carvacrol in PTZ-induced seizures in male mice and to investigate the role of N-Methyl-D-Aspartic Acid (NMDA) receptor. Methods. In the present experimental study, 90 mice were randomly divided into 9 groups (n=10). Drugs were injected intraperitoneally 30 minutes before PTZ injection. Then, seizure onset time, serum and brain antioxidant capacity (TAC) and malondialdehyde (MDA) and NMDA receptor gene expression in the hippocampus were examined. Results. Seizure onset time in the group received carvacrol (20 and 40 mg/kg) was significantly longer than the PTZ group (P&lt;0.05). Treatment with carvacrol (20 and 40 mg/kg) significantly increased serum and brain antioxidant capacity and reduced serum and brain MDA in compared to the PTZ group (at doses of 5, 10, 20 and 40 mg/kg). The expression of NR2A and NR2B subunits of hippocampal NMDA receptors in carvacrol-received mice was significantly lower than the PTZ group (P&lt;0.05). Conclusion. Carvacrol has anticonvulsant effects, possibly by inhibiting oxidative stress and reducing the expression of subunits of NMDA receptors.

Implication of nitrergic system in the anticonvulsant effects of ferulic acid in pentylenetetrazole-induced seizures in male mice.

Seizures are abnormal discharge of neurons in the brain. Ferulic acid (FA) is a phenolic compound with antioxidant and neuroprotective effects. The present study aimed to investigate the role of the nitrergic system in the anticonvulsant effect of FA in pentylenetetrazol (PTZ)-induced seizures in male mice. 64 male Naval Medical Research Institute (NMRI) mice weighing 25-29g were randomly divided into eight experimental groups (n=8). FA at doses 5, 10, and 40mg/kg alone and in combination with L-nitro-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) or L-arginine (L-arg) (nitric oxide [NO] precursor) was administrated (intraperitoneal). PTZ was injected (i.v. route) 30min after drugs administration (1mL/min). Seizure onset time was recorded and the nitrite levels of prefrontal cortex and serum were determined by the Griess method. FA at doses of 10 and 40mg/kg significantly increased the seizure threshold as well as reduced the serum and brain NO levels in comparison to the saline-received group. Co-administration of the effective dose of FA (10mg/kg) plus L-arg significantly decreased the seizure threshold in comparison to the effective dose of FA alone. Co-injection of the sub-effective dose of FA (5mg/kg) with L-NAME significantly increased the seizure threshold as well as significantly decreased the brain NO level in comparison to the sub-effective dose of FA alone. We showed that the nitrergic system, partially at least, mediated the anticonvulsant effect of FA in PTZ-induced seizures in mice. We concluded that L-NAME potentiated while L-arg attenuated the anticonvulsant effect of FA.

Seizure Forecasting Using Long-Term Electroencephalography and Electrocardiogram Data.

Electroencephalography (EEG) has been used to forecast seizures with varying success. There is an increasing interest to use electrocardiogram (ECG) to help with seizure forecasting. The neural and cardiovascular systems may exhibit critical slowing, which is measured by an increase in variance and autocorrelation of the system, when change from a normal state to an ictal state. To forecast seizures, the variance and autocorrelation of long-term continuous EEG and ECG data from 16 patients were used for analysis. The average period of recordings was 161.9 h, with an average of 9 electrographic seizures in an individual patient. The relationship between seizure onset times and phases of variance and autocorrelation in EEG and ECG data was investigated. The results of forecasting models using critical slowing features, seizure circadian features, and combined critical slowing and circadian features were compared using the receiver-operating characteristic curve. The results demonstrated that the best forecaster was patient-specific and the average area under the curve (AUC) of the best forecaster across patients was 0.68. In 50% of patients, circadian forecasters had the best performance. Critical slowing forecaster performed best in 19% of patients. Combined forecaster achieved the best performance in 31% of patients. The results of this study may help to advance the field of seizure forecasting and lead to the improved quality of life of people who suffer from epilepsy.

Rapamycin attenuates depression and anxiety-like behaviors through modulation of the NLRP3 pathway in pentylenetetrazole-kindled male Wistar rats.

There is cumulative evidence that shows the effect of epilepsy on behavioral conditions like anxiety and depression. The effects of rapamycin on anxiety and depression caused by pentylenetetrazole (PTZ) in the rat and possible underlying mechanisms were evaluated. Male Wistar rats were divided into experimental and control groups. The experimental groups were treated with intraperitoneal (i.p.) injection of 0.5, 1, and 2mg/kg of rapamycin, while the control group received normal saline only. Kindling was induced by sub-threshold dose (35mg/kg, i.p.) of PTZ for one month. When the kindling procedure was done, the seizure behaviors and the behavioral function were evaluated. For anxiety parameters, the elevated plus maze (EPM) was used. The forced swim test was employed to assess the antidepressant potential. At the end of the experiment, rats were euthanized and the blood serum and brain samples were isolated for respective measurement of oxidative stress and gene expression parameters. Rapamycin delayed the development of kindling and the onset time of seizures. Rapamycin administration reduced immobility time in the FST, exerting antidepressant-like activity. In the EPM test, rapamycin produced an anxiolytic-like effect. In addition, rapamycin increased the catalase and superoxide dismutase levels in the serum and significantly decreased the gene expression of I11b and Nlrp3 compared to the PTZ group. Our results showed that the inhibitory effect of mTOR inhibitor (rapamycin) on reactive oxygen species production during NLRP3 inflammasome activation could bring about behavioral alterations in anxiety and depression.

Video-EEG monitoring in diagnostics and treatment efficacy evaluation in newly-diagnosed generalized epilepsy in adults

Introduction. Video-electroencephalography (EEG) monitoring (VEEGM) is an indispensable functional method in epileptology. However, virtually no trials on assessing efficacy of antiepileptic drugs (AED) by using VEEGM are available.Objective: to improve efficacy of EEG-diagnostics and evaluate the epileptiform activity index (EAI) in newly-diagnosed idiopathic generalized epilepsy in adult patients receiving alproic acid and levetiracetam.Material and methods. T here w ere e nrolled 130 p atients: 6 0 (46.2%) m ales a nd 7 0 (53.8%) f emales w ith n ewlydiagnosedidiopathic generalized epilepsy (IGE), aged 22.51±8.9 years. All patients underwent VEEGM with quantitative EAI analysis at baseline visit and 1 3, 6 and 12 months later after treatment. Each seizure episode developed during the VEEGM study were assessed for type, time of seizure onset, relation to wake-sleep cycle, duration, ictal EEG pattern followed by diagnosing epileptic syndrome. Valproic acid and levetiracetam were used for initial therapy in groups per 65 patients in each. Treatment efficacy was assessed using parameters such as retention on therapy, absence of seizures, decrease of seizure frequency by &gt;50%, decrease of seizure frequency by &lt;50% – insufficient efficacy.Results. It was found that seizures during baseline VEEGM were recorded in 43.1% (n=56) patients, who were assigned to group 1, whereas remaining 74 (56.9%) patients were assigned to group 2. EAI was significantly higher in patients with seizures recoded at baseline VEEGM, compared to those lacking seizure episodes during initial VEEGM (p&lt;0,001), mean EAI was also higher in group I at second (p&lt;0.001) and third (p&lt;0.001) visits. EAI magnitude at 6 and 12 months of study became virtually comparable in all groups and did not depend on AED prescribed. Treatment efficacy was higher in patients with IGE, with no eizures recorded during the initial VEEGM.Conclusion. Long-term VEEGM allows unbiased assessment of treatment dynamics based on EAI analysis. The first 6 months of initial treatment titration in represent most crucial period for patients with newly-diagnosed IGE.

In vitro and In vivo Anticonvulsant Effect of Hydroalcoholic Extracts of Clutia abyssinica in Mice Model

Background: Epilepsy is a chronic disorder of the brain that affects people of all ages worldwide. In the search of safe and effective antiepileptics traditional treatment practices are one area of research to obtain novel molecules. Research is also needed to validate and standardize the traditional claim. Clutia abyssinica leaves were one of the medicinal plants claimed for use against epilepsy and evil eye and other diseases in different parts of Ethiopia. But there was no scientific research evidence for the claimed use of the plant. Therefore this work was designed to evaluate the anticonvulsant effect of hydroalcoholic extract of Clutia abyssinica leaves.&#x0D; Methods: The dry residue of the plant extract was used for the test. In vitro 0Mg2+ mice model at dose 0.7 mg/kg of extract, diazepam (3μM) and untreated brain slice groups were used to compare the presence of seizure like event (SLE). In vivo pentylenetetrazol (PTZ) model with 85 mg/kg subcutaneously was used to compare the seizure onset time with two extract doses and diazepam 5 mg/kg. The data was presented with mean± standard error. In maximum electric shock (MES) model 54 mA was passed for 0.2 second transauricularly in mice. The mean time of hind limb extension was recorded for doses 400 mg/kg and 800mg/kg of the extract and 10 mg/kg phenytoin. The means were compared for statistical significance using one way ANOVA post hoc LSD whereas proportions were compared using Fishers exact test with P-value &lt; .05. &#x0D; Results: In vitro anticonvulsant tests C. abyssinica extract effect was not statistically significant compared to negative control (P&gt;0.05).A positive control using the known anticonvulsant diazepam (3μM), showed significant anticonvulsant activity (P&lt;0.05). The in vivo PTZ test showed no statistically significant effect in plant extract at all dose levels (P&gt;0.05). In the in vivo MES test the extract of Clutia abyssinica both low and higher dose didn't show statistically significant effect (P&gt;0.05) compared with the negative control. But the extract improved survival (p&lt;0.05). The qualitative secondary metabolite test evidenced the presence of alkaloids, cardiac glycosides, flavanoids, phenols, saponins, sterols and terpeoids in Clutia abyssinica extract.&#x0D; Conclusion: The hydroalcoholic crude extract result of the C. abyssinica as anticonvulsant is weak based on the models used in this study. For most of the local preparation are mixes of different plants it may have synergistic action with other plants. Or it may have action with other models of chronic epilepsy.

Time domain based seizure onset analysis of brain signatures in pediatric EEG

A comprehensive insight into the epileptiform discharges at the time of seizure onset can aid neurophysiologists in the diagnosis and treatment of epileptic seizures. Visual analysis of seizure onset patterns is often a complex and tedious task. These problems suggest the development of automated seizure onset detection systems. The present research work is oriented for automatic detection of epileptic seizures at the onset using statistical measures. A quadratic classifier with fourfold cross-validation is used to demarcate the seizure and non-seizure activity. The algorithm is evaluated for 24 patients from the CHB MIT scalp EEG database. Classifier performance is assessed in terms of sensitivity, specificity, accuracy, and latency.

New-onset seizures after cranioplasty\u2014a different view on a putatively frequently observed phenomenon

BackgroundNew-onset seizures after cranioplasty (NOSAC) are reported to be a frequent complication of cranioplasty (CP) after decompressive hemicraniectomy (DHC). There are considerable differences in the incidence of NOSAC and contradictory data about presumed risk factors in the literature. We suggest NOSAC to be a consequence of patients’ initial condition which led to DHC, rather than a complication of subsequent CP. We conducted a retrospective analysis to verify our hypothesis.MethodsThe medical records of all patients ≥ 18 years who underwent CP between 2002 and 2017 at our institution were evaluated including incidence of seizures, time of seizure onset, and presumed risk factors. Indication for DHC, type of implant used, timing of CP, patient age, presence of a ventriculoperitoneal shunt (VP shunt), and postoperative complications were compared between patients with and without NOSAC.ResultsA total of 302 patients underwent CP between 2002 and 2017, 276 of whom were included in the outcome analysis and the incidence of NOSAC was 23.2%. Although time between DHC and CP differed significantly between DHC indication groups, time between DHC and seizure onset did not differ, suggesting the occurrence of seizures to be independent of the procedure of CP. Time of follow-up was the only factor associated with the occurrence of NOSAC.ConclusionNew-onset seizures may be a consequence of the initial condition leading to DHC rather than of CP itself. Time of follow-up seems to play a major role in detection of new-onset seizures.

Temporal patterns in the first unprovoked seizure

ObjectiveCyclic phenomena in epilepsy are well recognized. We investigated a multicenter cohort of unprovoked first seizure presentations to determine whether seizures have a preponderance to occur in: a particular time of the day, a particular day of the week, a particular month of the year, day time versus night time, and wakefulness versus sleep. MethodsWe retrospectively studied adults who presented with a first-ever unprovoked seizure to the First Seizure Clinic at two tertiary centers in Australia. Seizure onset time was obtained from the emergency department and ambulance documentations. Electro-clinical and neuroimaging findings were reviewed. We used histograms and Poisson regression modeling to determine whether seizures have a preponderance to occur at a particular time and calculated incidence rate ratios (IRR). We performed further analysis on patients with “first seizure epilepsy” and “first seizure not epilepsy” based on the ILAE criteria for a diagnosis of epilepsy after a single unprovoked seizure, as well as comparing patients that could be categorized as having a generalized-onset seizure versus those with focal–onset seizures. ResultsWe analyzed 1724 patients (38% females; age range 14–97 yr, median 39 yr), of whom 18% had epileptiform abnormalities on EEG and potentially epileptogenic lesions were detected on neuroimaging in 28%. Whole cohort analysis shows the incidence rate ratios (IRR) of seizures varied significantly across the 24-hour clock-time of the day (p < 0.001), peaking at hour 12 (IRR 3.18). The first unprovoked seizure was significantly less likely to be reported during the night (IRR 0.61, p < 0.001) and during sleep (IRR 0.29, p < 0.001). Both the “first seizure epilepsy” and “first seizure not epilepsy” subgroups’ analysis demonstrated similar patterns. An infraradian pattern was also noted with seizures most likely to occur in May (IRR 1.29, p = 0.02). Both “first seizure epilepsy – generalized” and “first seizure epilepsy – focal” groups had a preponderance for seizures to occur during the day versus night and wakefulness as opposed to sleep, but the association was more robust for generalized seizures. ConclusionsOur results suggest that temporal patterns are seen in patients with first-ever unprovoked seizures, including those that meet contemporary criteria for epilepsy. These results raise the possibility that first unprovoked seizures have intrinsic rhythmicity similar to epileptic seizures.

The prevalence of epileptic seizures in multiple sclerosis in a large tertiary hospital in Australia.

RationaleTo determine the prevalence of epileptic seizures in multiple sclerosis (MS) at an Australian tertiary hospital and to define their clinical features.MethodsWe retrospectively analysed adult patients at the Royal Melbourne Hospital electronically identified to have ICD codes for MS and seizures and/or epilepsy between 1996 to 2019, utilising paper and electronic-based records.ResultsOf the 2,125 MS patients identified, 16 (0.75%) experienced epileptic seizures during a mean follow-up period of 12.9 years. Median age of MS diagnosis (SD) was 38 (9.3) years. Four patients had relapsing remitting MS (25%), 10 secondary progressive MS (63.5%), and 2 primary progressive MS (12.5%). More than two-thirds of patients had seizure onset following the diagnosis of MS, and the majority of these had advanced disease (approximate EDSS >6) at the time of seizure onset. Focal onset-seizures occurred in 87.5% of patients with seizures.ConclusionThe estimated prevalence of seizures in our cohort was lower than in previous studies (0.75 vs 2–4%). In most cases, seizures occurred after the diagnosis of MS in the context of advanced disease. Further studies are required to determine if MS disease modifying treatments reduce the risk of seizures in this cohort.

Lamotrigine loaded PLGA nanoparticles intended for direct nose to brain delivery in epilepsy: pharmacokinetic, pharmacodynamic and scintigraphy study

The present study aimed to investigate the brain targeting efficacy of Lamotrigine (LTG) loaded PLGA nanoparticles (LTG-PNPs) upon intranasal administration. LTG-PNPs were fabricated through the emulsification-solvent evaporation technique and evaluated for % Entrapment efficiency, particle size, in-vitro release, surface morphology, crystallinity, ex-vivo permeation & thermal behaviour. Biodistribution, gamma scintigraphy, and pharmacodynamic studies were performed in BALB/c mice, New Zealand rabbits, and Wistar rats respectively. LTG-PNPs exhibited % EE 71%; particle size 170.0 nm; Polydispersity index 0.191; zeta potential −16.60 mV. LTG-PNPs exhibited a biphasic release pattern. Biodistribution and gamma scintigraphy studies proved a greater amount of LTG in the brain following intranasal delivery of LTG-PNPs in comparison to LTG-SOL. Pharmacodynamic studies demonstrated delayed seizure onset time with LTG-PNPs in comparison to LTG-SOL. Intranasal administration of LTG-PNPs provided prolonged release, higher bioavailability, and better brain targeting bypassing the BBB. The developed formulation could be administered as a once-a-day formulation that would reduce the dosing frequency; dose; dose-related side effects; cost of the therapy and would be beneficial in the management of epilepsy as compared to the LTG-SOL. However, the proof of concept generated through these studies needs to be further validated in higher animals and human volunteers.

The role of nitric oxide in anticonvulsant effects of lycopene supplementation on pentylenetetrazole-induced epileptic seizures in rats.

Recent studies have shown that natural antioxidant compounds have positive effects on the nervous system. Lycopene, the red pigment in tomatoes, is one of the potent natural antioxidants, and is used as supplementation because of its well-known health benefits. However, its effect on epileptic seizures and underlying mechanisms are still unclear. In this study, it was aimed to investigate the effect of lycopene on pentylenetetrazole-induced epileptic seizures in rats and to elucidate the nitric oxide pathway in this effect. In this study, thirty male Wistar albino rats were used. Animals were divided into five groups (n = 6 for each group) as control, saline (1mL/kg/day serum physiologic), positive control (2mg/kg/day diazepam), and lycopene (5 and 10mg/kg/day) for ten days. Pentylenetetrazole (45mg/kg) was given to induce a seizure in the tenth day except for the control. Passive avoidance test was carried out to evaluate memory function. Inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and nitric oxide (NO) levels were measured in the cortex and hippocampal brain regions using the ELISA kits. Lycopene supplementation prolonged epileptic seizure onset times and reduced seizure stages. Besides, lycopene supplementation improved memory impairment after seizures. Moreover, lycopene significantly reduced the level of iNOS, nNOS, and NO in the brain. Lycopene supplementation significantly alleviated seizures and memory impairment. Its anticonvulsive effect could be associated with the nitric oxide pathway. Lycopene supplementation could be useful as a supportive therapeutic agent in epileptic patients.