Majority Of Seizures Research Articles

Effects of Sublethal Organophosphate Toxicity and Anti-cholinergics on Electroencephalogram and Respiratory Mechanics in Mice

Organophosphates are used in agriculture as insecticides but are potentially toxic to humans when exposed at high concentrations. The mechanism of toxicity is through antagonism of acetylcholinesterase, which secondarily causes excess activation of cholinergic receptors leading to seizures, tremors, respiratory depression, and other physiological consequences. Here we investigated two of the major pathophysiological effects, seizures and respiratory depression, using subcutaneous injection into mice of the organophosphate diisopropylfluorophosphate (DFP) at sublethal concentrations (2.1 mg/Kg) alone and co-injected with current therapeutics atropine (50 mg/Kg) or acetylcholinesterase reactivator HI6 (3 mg/Kg). We also tested a non-specific cholinergic antagonist dequalinium chloride (2 mg/Kg) as a novel treatment for organophosphate toxicity. Electroencephalogram (EEG) recordings revealed that DFP causes focal delta frequency (average 1.4 Hz) tonic spikes in the parietal region that occur transiently (lasting an average of 171 ± 33 min) and a more sustained generalized theta frequency depression in both parietal and frontal electrode that did not recover the following 24 h. DFP also caused behavioral tremors that partially recovered the following 24 h. Using whole body plethysmography, DFP revealed acute respiratory depression, including reduced breathing rates and tidal volumes, that partially recover the following day. Among therapeutic treatments, dequalinium chloride had the most potent effect on all physiological parameters by reducing acute EEG abnormalities and promoting a full recovery after 24 h from tremors and respiratory depression. Atropine and HI6 had distinct effects on EEGs. Co-treatment with atropine converted the acute 1.4 Hz tonic spikes to 3 Hz tonic spikes in the parietal electrode and promoted a partial recovery after 24 h from theta frequency and respiratory depression. HI6 fully removed the parietal delta spike increase and promoted a full recovery in theta frequency and respiratory depression. In summary, while all anticholinergic treatments promoted survival and moderated symptoms of DFP toxicity, the non-selective anti-cholinergic dequalinium chloride had the most potent therapeutic effects in reducing EEG abnormalities, moderating tremors and reducing respiratory depression.

Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial

CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopathy characterised by severe global developmental impairment and seizures that can begin in the first few months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We aimed to further assess the efficacy and safety of ganaxolone in patients with CDD-associated refractory epilepsy. In the double-blind phase of this randomised, placebo-controlled, phase 3 trial, done at 39 outpatient clinics in eight countries (Australia, France, Israel, Italy, Poland, Russia, the UK, and the USA), patients were eligible if they were aged 2-21 years with a pathogenic or probably pathogenic CDKL5 variant and at least 16 major motor seizures (defined as bilateral tonic, generalised tonic-clonic, bilateral clonic, atonic, or focal to bilateral tonic-clonic) per 28 days in each 4-week period of an 8-week historical period. After a 6-week prospective baseline period, patients were randomly assigned (1:1) via an interactive web response system to receive either enteral adjunctive ganaxolone or matching enteral adjunctive placebo (maximum dose 63 mg/kg per day for patients weighing ≤28 kg or 1800 mg/day for patients weighing >28 kg) for 17 weeks. Patients, caregivers, investigators (including those analysing data), trial staff, and the sponsor (other than the investigational product manager) were masked to treatment allocation. The primary efficacy endpoint was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase and was analysed (using a Wilcoxon-rank sum test) in all patients who received at least one dose of trial treatment and for whom baseline data were available. Safety (compared descriptively across groups) was analysed in all patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov, NCT03572933, and the open-label extension phase is ongoing. Between June 25, 2018, and July 2, 2020, 114 patients were screened for eligibility, of whom 101 (median age 6 years [IQR 3 to 10]) were randomly assigned to receive either ganaxolone (n=50) or placebo (n=51). All patients received at least one dose of a study drug, but seizure frequency for one patient in the ganaxolone group was not recorded at baseline and so the primary endpoint was analysed in a population of 100 patients. There was a median percentage change in 28-day major motor seizure frequency of -30·7% (IQR -49·5 to -1·9) in the ganaxolone group and of -6·9% (-24·1 to 39·7) in the placebo group (p=0·0036). The Hodges-Lehmann estimate of median difference in responses to ganaxolone versus placebo was -27·1% (95% CI -47·9 to - 9·6). Treatment-emergent adverse events occurred in 43 (86%) of 50 patients in the ganaxolone group and in 45 (88%) of 51 patients in the placebo group. Somnolence, pyrexia, and upper respiratory tract infections occurred in at least 10% of patients in the ganaxolone group and more frequently than in the placebo group. Serious adverse events occurred in six (12%) patients in the ganaxolone group and in five (10%) patients in the placebo group. Two (4%) patients in the ganaxolone group and four (8%) patients in the placebo group discontinued the trial. There were no deaths in the double-blind phase. Ganaxolone significantly reduced the frequency of CDD-associated seizures compared with placebo and was generally well tolerated. Results from what is, to our knowledge, the first controlled trial in CDD suggest a potential treatment benefit for ganaxolone. Long-term treatment is being assessed in the ongoing open-label extension phase of this trial. Marinus Pharmaceuticals.

Influence of Febrile Seizure in Children’s Neurodevelopment

Background: Febrile seizure is one of the most common diseases in early childhood. The impact of early-life Febrile Seizure on the developing brain is an important issue to detect.
 Objectives: To observe the neurodevelopment of children suffering from different types of febrile seizures.
 Methods: This was a prospective observational study; the study was conducted in Dhaka Shishu (Children) Hospital, Dhaka from July 2012 to August 2013. Total 71 children were included in the study who fulfilled the selection criteria. History was taken thoroughly. Rapid neurodevelopmental assessment (RNDA) was performed for initial assessment and subsequent follow up and was advised accordingly.
 Results: Total 71 cases were included where mean age was 17.76±8.03 months, median was 16 months; in both the group male child had slight high preponderance. Majority of seizures were <10 minutes duration in both group which was not statistically significant. Important postictal event was found, 12 cases (26.7%) in simple seizure and 16 cases (61.5%) in complex seizures which was found statistically significant, but there was no risk for further seizure. On follow up, RNDA detected risk of impairment in vision, cognition, speech and behavior. In complex group statistically significant association was found with impairment of cognition only at initial and follow up at 3 month.
 Conclusion: Neurodevelopment impairment is not influenced by types of febrile seizure but significant cognitive impairment was found in complex seizure.
 DS (Child) H J 2021; 37(1): 45-50

Seizures and Epilepsy in Childhood.

This article highlights basic concepts of seizures and epilepsy in pediatric patients, as well as basic treatment principles for this age group. Epilepsy is the most common neurologic disorder in childhood. Accurate diagnosis is key; in older children, epileptic seizures need to be differentiated from various paroxysmal nonepileptic events, whereas in neonates, the majority of seizures are subclinical (electroencephalographic). Antiseizure medications remain the first-line treatment, but ketogenic diet and epilepsy surgery have also shown positive outcomes and can decrease drug burden. Genetic causes account for approximately 30% of cases, and the recognition of electroclinical syndromes is being replaced by the concept of genetic spectrums. Precision medicine therapies are promising, but wide application in daily practice still has a long way to go. Early access to specialist centers and optimal treatments positively affects prognosis and future neurodevelopment. Although novel findings from all fields of research are being incorporated into everyday clinical practice, a better quality of life for children with seizures and epilepsy and their families is the ultimate priority.

Semiautomated classification of nocturnal seizures using video recordings.

The objective of this study was to evaluate the accuracy of a semiautomated classification of nocturnal seizures using a hybrid system consisting of an artificial intelligence-based algorithm, which selects epochs with potential clinical relevance to be reviewed by human experts. Consecutive patients with nocturnal motor seizures admitted for video-electroencephalographic long-term monitoring (LTM) were prospectively recruited. We determined the extent of data reduction by using the algorithm, and we evaluated the accuracy of seizure classification from the hybrid system compared with the gold standard of LTM. Forty consecutive patients (24male; median age = 15years) were analyzed. The algorithm reduced the duration of epochs to be reviewed to 14% of the total recording time (1874h). There was a fair agreement beyond chance in seizure classification between the hybrid system and the gold standard (agreement coefficient = .33, 95% confidence interval = .20-.47). The hybrid system correctly identified all tonic-clonic and clonic seizures and 82% of focal motor seizures. However, there was low accuracy in identifying seizure types with more discrete or subtle motor phenomena. Using a hybrid (algorithm-human) system for reviewing nocturnal video recordings significantly decreased the workload and provided accurate classification of major motor seizures (tonic-clonic, clonic, and focal motor seizures).

Genotype and phenotype of children with DEPDC5 gene variants related epilepsy

Objective: To summarize the clinical characteristics and the features of electroencephalograph (EEG) of children with DEPDC5 gene variants related epilepsy. Methods: The clinical data, gene variation, EEG and head magnetic resonance image (MRI) of 20 epileptic children with DEPDC5 gene variants admitted to Department of Pediatrics, Peking University First Hospital from May 2017 to November 2020 were retrospectively analyzed. Results: Twenty patients with heterozygous DEPDC5 gene variants were enrolled, 8 of 20 patients were nonsense variants, 6 were missense variants, 3 were frame-shift variants, 2 were splicing variants, and 1 was large fragment deletion. Sixteen cases had hereditary variation and 4 had de novo variation. Fifteen of variations were novel. Nine were male, while 11 were female. Their latest follow-up age ranged from 10 months to 13 years and one month.The epilepsy onset age ranged from 3 hours to 11 years and 3 months, the median age was 10.5 months. Twelve (60%) patients had developmental delay. Nineteen patients had focal seizures, 7 had epileptic spasms, 1 had multiple seizure types including tonic, atypical absence, dystonic and myoclonic seizures. Epileptic form discharges were observed in 18 patients during the interictal phase, and 11 were focal discharges, 7 were multifocal discharges. Ten (50%) patients had abnormal brain MRI, including focal cortical dysplasia in 5 patients, undefined malformation of cortical development in 4 patients, hemimegalencephaly in 1 patient. Four patients were diagnosed as West syndrome and one patient was diagnosed as Lennox-Gastaut syndrome. Fourteen (70%) patients were diagnosed as drug-resistant epilepsy. Four patients became seizure-free by treatment with anti-epileptic drugs. Three children were treated with surgery, and 2 of them became seizure-free, 1 had more than 75% reduction in seizures. Conclusions: DEPDC5 gene variant epilepsy is inherited with incomplete penetrance and focal seizure is the major seizure type. However, epileptic spasms, generalized seizures can also be observed. Half of the patients brain malformations. Most of the patients are drug-resistant epilepsy. Patients with clear epileptogenic zones can be treated with surgery. Treatment-resistant patients are more likely to be complicated with developmental delay.

Parental experiences and perspectives on the value of seizure detection while caring for a child with epilepsy: A qualitative study

IntroductionCaring for a child with epilepsy has a significant impact on parental quality of life. Seizure unpredictability and complications, including sudden unexpected death in epilepsy (SUDEP), may cause high parental stress and increased anxiety. Nocturnal supervision with seizure detection devices may lower SUDEP risk and decrease parental burden of seizure monitoring, but little is known about their added value in family homes. MethodsWe conducted semi-structured in-depth interviews with parents of children with refractory epilepsy participating in the PROMISE trial (NCT03909984) to explore the value of seizure detection in the daily care of their child. Children were aged 4–16 years, treated at a tertiary epilepsy center, had at least one nocturnal major motor seizure per week, and used a wearable seizure detection device (NightWatch) for two months at home. Data were analyzed using inductive thematic analysis. ResultsTwenty three parents of nineteen children with refractory epilepsy were interviewed. All parents expressed their fear of missing a large seizure and the possible consequences of not intervening in time. Some parents felt the threat of child loss during every seizure, while others thought about it from time to time. The fear could fluctuate over time, mainly associated with fluctuations of seizure frequency. Most parents described how they developed a protective behavior, driven by this fear. The way parents handled the care of their child and experienced the burden of care influenced their perceptions on the added value of NightWatch. The experienced value of NightWatch depended on the amount of assurance it could offer to reduce their fear and the associated protective behavior as well as their resilience to handle the potential extra burden of care, due to false alarms or technical problems. ConclusionHealthcare professionals and device companies should be aware of parental protective behavior and the high parental burden of care and develop tailored strategies to optimize seizure detection device care.

Prediction of tuberous sclerosis-associated neurocognitive disorders and seizures via machine learning of structural magnetic resonance imaging

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by multiorgan hamartomas, including cerebral lesions, with seizures as a common presentation. Most TSC patients will also experience neurocognitive comorbidities. Our objective was to use machine learning techniques incorporating clinical and imaging data to predict the occurrence of major neurocognitive disorders and seizures in TSC patients. A cohort of TSC patients were enrolled in this retrospective study. Clinical data included genetic, demographic, and seizure characteristics. Imaging parameters included the number, characteristics, and location of cortical tubers and the presence of subependymal nodules, SEGAs, and cerebellar tubers. A random forest machine learning scheme was used to predict seizures and neurodevelopmental delay or intellectual developmental disability. Prediction ability was assessed by the area-under-the-curve of receiver-operating-characteristics (AUC-ROC) of ten-fold cross-validation training set and an independent validation set. The study population included 77 patients, 55% male (17.1 ± 11.7years old). The model achieved AUC-ROC of 0.72 ± 0.1 and 0.68 in the training and internal validation datasets, respectively, for predicting neurocognitive comorbidity. Performance was limited in predicting seizures (AUC-ROC of 0.54 ± 0.19 and 0.71 in the training and internal validation datasets, respectively). The integration of seizure characteristics into the model improved the prediction of neurocognitive comorbidity with AUC-ROC of 0.84 ± 0.07 and 0.75 in the training and internal validation datasets, respectively. This proof of concept study shows that it is possible to achieve a reasonable prediction of major neurocognitive morbidity in TSC patients using structural brain imaging and machine learning techniques. These tools can help clinicians identify subgroups of TSC patients with an increased risk of developing neurocognitive comorbidities.

Efficacy and safety of using vagus nerve stimulation in patients with pharmacoresistant epilepsy in the Russian Federation: a multi-center retrospective observational program

Objective: to assess efficacy and safety of vagus nerve stimulation (VNS) in patients with pharmacoresistant epilepsy.Material and methods. A multi-center retrospective observational program was applied in patients with pharmacoresistant epilepsy by using vagus nerve stimulation for at least 2 years. There were enrolled 151 subjects, patient age on stimulator implantation varied from 5 to 65 years (24.4±13.1 years). Among them, subjects under 18 or at least 18 years of age comprised 58 (38.4%) and 93 (61.6%), respectively. Changes in rate and severity of major group epileptic seizures (highly disabling type) 24 months after VNS-therapy vs. baseline state as well as during 3-, 6-, 9-, 12-month follow-up were compared. There were assessed stimulator-related effects on VNS-therapy as well as patient quality of life 2 years after therapy. The dynamics of the frequency of all types of epileptic seizures was evaluated according to McHugh Outcome scale.Results. Mean epilepsy duration on stimulator implantation was 170.9±126.8 months, with maximum up to 666 months (55 years). Number of patients with dominant (disabling) seizures on implantation procedure comprised 136 (90.1%). Decline in dominant epileptic seizure rate by 50–99% was recorded in 91 patients (66.9%) 24 months after VNStherapy. Among such subjects were 41 patients (30.15%) featured with disabling seizures including 24 fully seizure free subjects (17.65%). Decreased rate of all group epileptic seizures by more than 50% (responders) was found in 52.9% cases, including subjects under 18 and adults in 63.9% and as few as 46.3% (p<0.05), respectively. While assessing dynamic rate for all groups of epileptic seizures applied with VNS-therapy by using McHugh Outcome scale it was found that class I (lowered seizure rate by 80–100%) was observed in 44 cases (29.1%), including 18 patients under 18 (31%) and 26 subjects above 18 (28%) (insignificant difference). Mean dominant group epileptic seizure rate was also significantly decreased in both age groups from 20 down to 5.7 per month. Severity of epileptic seizures and postseizure condition upon VNS-therapy was decreased in 38.6% and 43.9% patients 24 months after therapy and on final follow-up visit, respectively (more than 24 months after implantation). No serious adverse events as well as adverse effects resulting in therapy cancel were noted. Conclusion. Vagus nerve stimulation is an effective and safe auxiliary treatment method for therapy of pharmacoresistant epilepsy both in children and adults.><0.05) , respectively. While assessing dynamic rate for all groups of epileptic seizures applied with VNS-therapy by using McHugh Outcome scale it was found that class I (lowered seizure rate by 80–100%) was observed in 44 cases (29.1%), including 18 patients under 18 (31%) and 26 subjects above 18 (28%) (insignificant difference). Mean dominant group epileptic seizure rate was also significantly decreased in both age groups from 20 down to 5.7 per month. Severity of epileptic seizures and postseizure condition upon VNS-therapy was decreased in 38.6% and 43.9% patients 24 months after therapy and on final follow-up visit, respectively (more than 24 months after implantation). No serious adverse events as well as adverse effects resulting in therapy cancel were noted.Conclusion. Vagus nerve stimulation is an effective and safe auxiliary treatment method for therapy of pharmacoresistant epilepsy both in children and adults.

Characterization of Seizure Induction Methods in Drosophila.

Epilepsy is one of the most common neurologic disorders. Around one third of patients do not respond to current medications. This lack of treatment indicates a need for better understanding of the underlying mechanisms and, importantly, the identification of novel targets for drug manipulation. The fruit fly Drosophila melanogaster has a fast reproduction time, powerful genetics, and facilitates large sample sizes, making it a strong model of seizure mechanisms. To better understand behavioral and physiological phenotypes across major fly seizure genotypes we systematically measured seizure severity and secondary behavioral phenotypes at both the larval and adult stage. Comparison of several seizure-induction methods; specifically electrical, mechanical and heat induction, show that larval electroshock is the most effective at inducing seizures across a wide range of seizure-prone mutants tested. Locomotion in adults and larvae was found to be non-predictive of seizure susceptibility. Recording activity in identified larval motor neurons revealed variations in action potential (AP) patterns, across different genotypes, but these patterns did not correlate with seizure susceptibility. To conclude, while there is wide variation in mechanical induction, heat induction, and secondary phenotypes, electroshock is the most consistent method of seizure induction across known major seizure genotypes in Drosophila.

Cannabidiol modifies the seizure expression and effects of antiseizure drugs in a rat model of recurrent severe seizures

PurposeTo evaluate the effects of cannabidiol alone or in combination with antiseizure drugs in the expression of recurrent generalized seizures in a rat model. MethodsGroup A: Male Wistar rats received 3-mercaptopropionic acid (MP) every 12 h for 5 days to induce recurrent generalized seizures. Thereafter, the animals were submitted to a crossover protocol to receive different treatments with cannabidiol, phenytoin and phenobarbital, alone and in combination. Group B: Rats were manipulated as group A, but they received cannabidiol during the induction of recurrent seizures. ResultsMinor and major seizures were induced after each MP administration. Status epilepticus (SE) detected during the last MP administrations was considered a sign of high seizure severity. Cannabidiol did not modify the expression of the MP induced seizures but reduced the prevalence of SE in both experimental groups. Phenytoin decreased the expression of major seizures but did not modify the prevalence of SE (groups A and B). Cannabidiol combined with phenytoin did not modify these effects. Phenobarbital diminished the expression of major seizures, an effect more evident when combined with cannabidiol (groups A and B). The combination of phenobarbital and cannabidiol reduced the expression of SE of group B. The mortality rate of groups A and B at the end of the crossover protocol was 30% and 9%, respectively (p=0.2). ConclusionCBD associated with appropriate antiseizure drugs reduces the severity and prevalence of generalized seizures. In contrast, CBD alone reduces the seizure severity, but does not avoid the expression of generalized seizures.

Vortioxetine increases absence-like seizures in WAG/Rij rats but decreases penicillin- and pentylenetetrazole-induced seizures in Wistar rats

AimDepression is the major psychiatric disorder in patients with epilepsy. Vortioxetine is a novel antidepressant drug for the treatment of major depressive disorders. In the present study, effects of vortioxetine were evaluated in different experimental epilepsy models of rats. Materials and methodsFifty-six adult male Wistar rats and 28 WAG/Rij rats were divided into 12 groups of 7 rats each. Experiments were conducted with penicillin (500 IU, i.c.) and pentylenetetrazole models (50 mg/kg, intraperitoneally (i.p.)) in Wistar rats and genetic absence epileptic WAG/Rij rats. The vortioxetine (1, 5, or 10 mg/kg, i.p.) was evaluated in these three models. All groups were compared with their control groups. ResultsIn the penicillin-induced seizure model, 1, 5, or 10 mg/kg vortioxetine administration significantly decreased mean spike frequency. In the pentylenetetrazole-induced seizure model, 1, 5, or 10 mg/kg vortioxetine demonstrated a significant dose-dependent decrease in mean spike frequency, an increase in the latency to minor and major seizures, and a decrease in total duration of major seizure and convulsion stage. In genetic absence epileptic WAG/Rij rats, 1 mg/kg vortioxetine caused no significant alteration in the number and duration of SWDs compared to the controls, while 5 and 10 mg/kg doses of vortioxetine increased the number and duration of SWDs. Amplitude of the epileptiform activity did not change in any of the experimental epilepsy models. ConclusionThe results of this study suggested that vortioxetine has anticonvulsant activity in penicillin- and pentylenetetrazole-induced seizure models. However, it exhibited proconvulsant activity in the absence epileptic WAG/Rij rats.

A reappraisal of injuries and accidents in people with epilepsy.

We review data on injuries and traffic accidents affecting people with epilepsy with emphasis on the overall risk of injuries, specific types of injuries, and risk factors. Population-based studies of incident epilepsy cohorts indicate that the risk of physical injuries in people with epilepsy in general is increased only modestly. The risk is higher in selected populations that attend epilepsy clinics or referral centers. Soft tissue injuries, dislocations, and fractures are the most common injures, whereas the greatest increase in risk is reported for more uncommon injuries such as drowning. People with epilepsy are at a two-fold to four-fold increased risk for fatal injuries. Comorbidities contribute to fatal as well as nonfatal injuries. The other major risk factor is poorly controlled major convulsive seizures (generalized as well as focal to bilateral tonic-clonic seizures). Serious transport accidents associated with increased risks for people with epilepsy include pedestrian, bicycle, as well as car accidents. Individualized information on the risk of physical injuries and accidents should be part of counseling of patients with epilepsy. Improved seizure control is likely the most effective way to reduce risks, but work place and home adjustments should also be considered.

Bearing all Down Under: the role of Australasian countries in the illegal bear trade

Context Illegal wildlife trade (IWT) is a leading concern for conservation and biosecurity agencies globally, and involves multiple source, transit, and destination countries smuggling species on a transnational scale. The contribution of non-range countries for driving demand in IWT is often overlooked. Aims We analysed the dynamics (source, type and quantity) of bear seizures in Australia and New Zealand to gain a deeper understanding of the IWT, and to raise awareness among enforcement agencies for mitigating the international smuggling of bear parts and derivatives, and reducing the global threat to bears from illegal exploitation. Methods We collated biosecurity and conservation enforcement agency records of CITES seizures from Australia and New Zealand. All of the seizures were declared for ‘personal use’. Key results We report on 781 seizures of bear parts and derivatives in Australia and New Zealand from 33 countries over the past decade. The majority of seizures were medicinal (gall bladder and bile) products, but also included a range of body parts, hunting trophies and meat. China was the source of the greatest number of seizures, however, 32 additional source and transit countries/territories (from Asia, Europe, Americas, Middle East and Africa) were also involved in the seizures of bear parts and their derivatives. Conclusions The widespread trade of bears is an example of the far-reaching consequences commercial use can have on threatened species. Australia and New Zealand have no native bear species, and yet are frequently involved in wildlife seizures, and illegal bear trade continues to be an enforcement issue. Implications IWT has a detrimental impact on the conservation of bears. Conservation research in non-range countries needs to be conducted to determine the demand and threats from IWT, and to increase collaborative strategies to counter transnational smuggling.

Noninvasive transcranial focal stimulation affects the convulsive seizure-induced P-glycoprotein expression and function in rats

Transcranial focal stimulation (TFS) is a noninvasive neuromodulation strategy that reduces seizure activity in different experimental models. Nevertheless, there is no information about the effects of TFS in the drug-resistant phenotype associated with P-glycoprotein (Pgp) overexpression. The present study focused on determining the effects of TFS on Pgp expression after an acute seizure induced by 3-mercaptopropionic acid (MPA). P-glycoprotein expression was analyzed by western blot in the cerebral cortex and hippocampus of rats receiving 5 min of TFS (300 Hz, 50 mA, 200 μs, biphasic charge-balanced squared pulses) using a tripolar concentric ring electrode (TCRE) prior to administration of a single dose of MPA. An acute administration of MPA induced Pgp overexpression in cortex (68 ± 13.4%, p < 0.05 vs the control group) and hippocampus (48.5 ± 14%, p < 0.05, vs the control group). This effect was avoided when TFS was applied prior to MPA. We also investigated if TFS augments the effects of phenytoin in an experimental model of drug-resistant seizures induced by repetitive MPA administration. Animals with MPA-induced drug-resistant seizures received TFS alone or associated with phenytoin (75 mg/kg, i.p.). TFS alone did not modify the expression of the drug-resistant seizures. However, TFS combined with phenytoin reduced seizure intensity, an effect associated with a lower prevalence of major seizures (50%, p = 0.03 vs phenytoin alone). Our experiments demonstrated that TFS avoids the Pgp overexpression induced after an acute convulsive seizure. In addition, TFS augments the phenytoin effects in an experimental model of drug-resistant seizures. According with these results, it is indicated that TFS may represent a new neuromodulatory strategy to revert the drug-resistant phenotype.

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program

IntroductionAn intermediate-sized, multicenter, expanded-access study was opened in 2015 through the support of the State of Georgia. This study provided children with treatment-resistant epilepsy (TRE) access to plant-derived highly purified cannabidiol (CBD; Epidiolex® in the US; Epidyolex® in the EU; 100 mg/mL oral solution). These children had failed to achieve seizure freedom with available treatment options and were ineligible to participate in randomized controlled trials that only included patients with Lennox–Gastaut and Dravet syndromes. MethodsCannabidiol safety, changes in seizure type, frequency, and seizure-free days were evaluated for children aged 1–18 years (at time of consent) as an adjunctive treatment for 36 months. The study consisted of a two-month baseline period, a titration period, treatment period, and optional titration period, which occurred after ≥26 weeks of treatment. Cannabidiol treatment was administered up to a targeted dose of 25 mg/kg/day, with an optional secondary treatment up to 50 mg/kg/day. Daily seizure type, seizure frequency, and seizure-free days were recorded in a Web-based diary, and changes in these outcomes were recorded and analyzed for the duration of the study. The occurrence of adverse events (AEs) was also recorded. ResultsThe median percentage change in seizures for 45 patients in Months 3, 6, 12, 18, 24, and 36 showed a statistically significant (p < 0.001) reduction in major seizures (ranging from 54 to 72% at various time points) and all seizures (61–70%) compared with baseline. A mean increase in seizure-free days per 28 days was >5 in all treatment periods after Month 2, and an average increase of 7.52 (p < 0.001) seizure-free days per 28 days was observed at the end of follow-up compared with baseline. All patients experienced ≥1 AE. Children who transitioned to the optional secondary treatment (high-dose group) reported more AEs before increasing their dose to >25.0 mg/kg/day compared with the low-dose group. However, the average rate of AEs was significantly lower after moving to a high-dose regimen (p = 0.004). Twelve children reported 20 serious AEs, none of which were considered related to CBD. ConclusionsThis study supports CBD as an adjunctive treatment for children with TRE. Treatment was well tolerated in doses up to 50 mg/kg/day. Patients who did not achieve desired results at a dose of ≤25.0 mg/kg/day reported more AEs when CBD dose increased to >25.0 mg/kg/day. Decreases in major seizure frequency and an increase in seizure-free days compared with baseline were reported during treatment. This supports the efficacy and tolerability of CBD for mixed seizure etiologies.

Seizures with paroxysmal arousals in sleep-related hypermotor epilepsy (SHE): Dissecting epilepsy from NREM parasomnias.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy characterized by seizures occurring mostly during sleep, ranging from brief seizures with paroxysmal arousals (SPAs) to hyperkinetic seizures and ambulatory behaviors. SPAs are brief and stereotypic seizures representing the beginning of a major seizure. Distinguishing SPAs from disorders of arousal (DOAs) and their briefest episodes called simple arousal movements (SAMs) is difficult. We performed a characterization of SPAs and SAMs to identify video-polysomnographic (VPSG) features that can contribute to the diagnosis of SHE or DOA. Fifteen SHE, 30 DOA adult patients, and 15 healthy subjects underwent full-night VPSG. Two neurologist experts in sleep disorders and epilepsy classified all the sleep-related movements and episodes recorded. For each SPAs and SAMs, sleep stage at onset, duration, limb involvement, progression, and semiology have been identified. A total of 121 SPAs were recorded, emerging mostly during stage 1-2 non-rapid eye movement (NREM) sleep (median duration: 5seconds). At the beginning, the SPAs motor pattern was hyperkinetic in 78 cases (64%), involving more than three non-contiguous or all body parts. The standard was a constant progression of movements during SPAs without any motor arrests. In DOA patients a total of 140 SAMs were recorded (median duration: 12seconds) mostly emerging during stage 3 NREM sleep. In SAMs, we did not observe any tonic/dystonic or hypermotor patterns or stereotypy; motor arrest was present over the course of about half of the episodes. In comparison with both DOA and healthy subjects, SHE patients showed a higher number of sleep-related movements per night and a reduction of sleep efficiency. SPAs and SAMs present different semiological and clinical features. Their recognition could be useful to drive the diagnosis when major episodes are not recorded during VPSG in patients with a clear clinical history of SHE or DOA.

To observe the clinical presentation of seizure disorder in 0-1 month age group

This prospective study was conducted over the period of one year at M.Y. Hospital &amp; Chacha Nehru Bal Chikitsalaya, Indore, in the Department of Pediatrics, M.G.M. Medical College, Indore.Detailed history of present illness with duration of convulsion were enquired. A detailed history of mother during antenatal, natal and post natal period was taken. Type of delivery (vaginal/ LSCS ; full term / preterm), enquired about the indication of LSCS. History of labour with particular ref to birth injury, asphyxia (delayed cry), neonatal history regarding jaundice &amp; feeding history, detailed family history in relation to epilepsy convulsion and mental diseases were recorded. Out of 100 cases 64% were males and 36% were females. Male female ratio was 1.77:1. Male cases were predominantly present in all 3 age groups. Majority of seizures occurred within 24 hrs. P value is not significant. Out of 100 cases 43 had tonic convulsions, 38 had subtle, and 19 had focal convulsions.43 neonates had seizures in 1st 24 hrs. Subtle seizures (60%) were most common followed by tonic seizures (32.5%) and then focal seizures (7.5%). In 2 – 7 day age group tonic seizures (42.8%) were most common followed by focal seizures (38%). In &amp;#62; 7 day age group also tonic seizures (73.6%) were most common. P value was &amp;#60; 0.001. Detailed clinical examination was done &amp; investigations were carried out in all patients. Cranial USG, EEG, &amp; CT scan were done as per requirement. Out of total 100 cases 74 were full term &amp; 26 were preterm. In our study maximum no. of cases developed seizure within 1st 24 hrs (43%) of life followed by 42% in 2–7 day age group &amp; 15% after 7 days. Convulsions were more common in males (64%) in all age group.

P1856KIDNEY CRISES: USING IN SITU SIMULATION TEACHING TO FACILITATE MULTIDISCIPLINARY TEAM WORKING IN RENAL EMERGENCIES

Abstract Background and Aims The haemodialysis unit is a unique clinical environment. Specialist nursing staff look after patients, frequently without on-site medical cover, and need to manage medical issues until help arrives. Junior doctors often have limited experience managing renal patients and may not be aware of specialty-specific issues when dealing with medical emergencies. The different skill sets in these groups creates an opportunity for shared learning. Simulation teaching provides a safe environment for individuals to develop communication, team working and clinical skills and helps facilitate discussion and reflection on clinical scenarios. We describe a programme of renal in situ simulation sessions for nurses and junior doctors to allow them to practise their roles in an emergency and evaluate feedback on their perception of the programme. Method Seventeen hour-long simulation sessions were delivered between June 2017 and January 2020 within the renal ward in 2 hospitals and in a satellite outpatient dialysis unit. They utilised a high-fidelity SimMan® mannequin. Scenarios were based on common or rare-but-serious medical emergencies (hyperkalaemic cardiac arrest, arrhythmia on dialysis, air embolism, major haemorrhage post-renal biopsy, line sepsis, hypertensive seizure, pulmonary oedema and drug-induced anaphylaxis). Sessions comprised an orientation to the mannequin, a clinical scenario and a debrief discussion. Doctors and nurses completed post-tutorial feedback exploring their thoughts on the programme. Results 59 healthcare professionals (40 doctors and 19 nurses) participated and completed post-event feedback. All attendees felt that sessions improved their knowledge and increased their confidence in managing similar scenarios in the future. They all felt they would be able to apply their learning to their day job. 86% of participants strongly agreed that the programme helped them develop stronger relationships with colleagues. In white-space boxes, individuals described the sessions as being helpful in developing communication, teamwork, leadership and delegation skills in addition to specific learning points for the individual scenarios. Sessions also identified practical issues, such as where to source medications or monitoring equipment, and led to the creation of an updated protocol folder and distribution of Advanced Life Support algorithms throughout the ward. Conclusion Nurses and junior doctors report increased confidence in managing medical emergencies in renal patients and improved relationships with colleagues following a simulation training programme. The programme promotes a learning culture within the unit. It provides an opportunity to discuss potentially serious situations and allows reflection on similar scenarios encountered within the ward and dialysis unit. Further work is needed to determine if in situ simulation teaching has an impact on patient outcome measures.

Peri-ictal heart rate variability parameters as surrogate markers of seizure severity.

This study aims at defining objective parameters reflecting the severity of peri-ictal autonomic changes and their relation to post-ictal generalized electroencephalography (EEG) suppression (PGES), with the view that such changes could be detected by wearable seizure detection systems and prove useful to assess the risk of sudden unexpected death in epilepsy (SUDEP). To this purpose, we assessed peri-ictal changes in heart rate variability (HRV) and correlated them with seizure duration, intensity of electromyography-based ictal muscle activity, and presence and duration of post-ictal generalized EEG suppression (PGES). We evaluated 75 motor seizures from 40 patients, including 61 generalized tonic-clonic seizures (GTCS) and 14 other major motor seizure types. For all major motor seizures, HRV measurements demonstrated a significantly decreased parasympathetic activity and increased sympathetic activity in the post-ictal period. The post-ictal increased sympathetic activity was significantly higher for GTCS as compared with non-GTCS. The degree of peri-ictal decreased parasympathetic activity and increased sympathetic activity was associated with longer PGES (>20s), longer seizure duration, and greater intensity of ictal muscle activity. Mean post-ictal heart rate (HR) was an independent predictor of PGES duration, seizure duration, and intensity of ictal muscle contraction. Our results indicate that peri-ictal changes in HRV are potential biomarkers of major motor seizure severity.