BACKGROUND & AIMS: OBJECTIVE:This paper explores the issues that arise from the discussion of administering rescue medication to children who experience prolonged convulsive seizures in mainstream schools in the UK. SITUATION ANALYSIS:Current guidelines recommend immediate treatment of children with such seizures (defined as seizures lasting more than 5 min) to prevent progression to status epilepticus and neurological morbidity. As children are unconscious during prolonged convulsive seizures, whether or not they receive their treatment in time depends on the presence of a teacher or other member of staff trained and able to administer rescue medication. However, it is thought that the situation varies between schools and depends mainly on the goodwill and resources available locally. RECOMMENDATIONS:A more systematic response is needed to ensure that children receive rescue medication regardless of where their seizure occurs. Possible ways forward include: greater use of training resources for schools available from epilepsy voluntary sector organisations; consistent, practical information to schools; transparent guidance outlining a clear care pathway from the hospital to the school; and implementation and adherence to each child's individual healthcare plan. IMPLICATIONS:Children requiring emergency treatment for prolonged convulsive seizures during school hours test the goals of integrated, person-centred care as well as joined-up working to which the National Health Service (NHS) aspires. As changes to the NHS come into play and local services become reconfigured, every effort should be made to take account of the particular needs of this vulnerable group of children within broader efforts to improve the quality of paediatric epilepsy services overall.

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BACKGROUND & AIMS: PURPOSE:To identify barriers to implementation of an evidence based integrated care pathway (ICP) for seizure management in the Emergency Department (ED). METHODS:A site specific bespoke questionnaire was designed to solicit anonymous responses from all grades of ED medical and nursing staff to a series of questions regarding utility, feasibility, significance and implementation of a locally designed and championed ICP for seizure management and onward referral. RESULTS:While 95% of respondents agreed that the pathway ensured patients were treated according to best practice, a number of human factors were identified as barriers to use. These fell into three categories 1) environmental 2) pathway design/process and 3) user related issues. CONCLUSIONS:Most respondents understood and endorsed the evidence based utility of the pathway. Barriers to use, however, are broad with interactions involving many complex human factors. Nevertheless, solutions can be relatively easily formulated but departmental-wide effort is required to comprehensively address all issues.

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BACKGROUND & AIMS: :Seizures have both local and remote effects on nervous system function. Whereas propagated seizures are known to disrupt cerebral activity, little work has been done on remote network effects of seizures that do not propagate. Human focal temporal lobe seizures demonstrate remote changes including slow waves on electroencephalography (EEG) and decreased cerebral blood flow (CBF) in the neocortex. Ictal neocortical slow waves have been interpreted as seizure propagation; however, we hypothesize that they reflect a depressed cortical state resembling sleep or coma. To investigate this hypothesis, we performed multimodal studies of partial and secondarily generalized limbic seizures in rats. Video/EEG monitoring of spontaneous seizures revealed slow waves in the frontal cortex during behaviorally mild partial seizures, contrasted with fast polyspike activity during convulsive generalized seizures. Seizures induced by hippocampal stimulation produced a similar pattern, and were used to perform functional magnetic resonance imaging weighted for blood oxygenation and blood volume, demonstrating increased signals in hippocampus, thalamus and septum, but decreases in orbitofrontal, cingulate, and retrosplenial cortex during partial seizures, and increases in all of these regions during propagated seizures. Combining these results with neuronal recordings and CBF measurements, we related neocortical slow waves to reduced neuronal activity and cerebral metabolism during partial seizures, but found increased neuronal activity and metabolism during propagated seizures. These findings suggest that ictal neocortical slow waves represent an altered cortical state of depressed function, not propagated seizure activity. This remote effect of partial seizures may cause impaired cerebral functions, including loss of consciousness.

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BACKGROUND & AIMS: OBJECTIVE:Febrile seizures (FS) are the most common convulsions in childhood. Interleukin-1beta (IL-1β) is proposed to play an important role in the development of FS, from in vitro data and data from peripheral blood samples. IL-1β secretion is needed for activation of the NLR family, pyrin-domain containing 3(NLRP3) inflammasome. However, whether NLRP3 play a role in the development of FS remains unknown. This study aimed to investigate the role of NLRP3 in FS. METHODS:Thirty-two FS cases and twenty-two matched controls were included in this study. Control samples were collected from children with febrile illness without seizures. We detected their levels of IL-1β and NLRP3 by Enzyme linked immunosorbent assay and Western blot, respectively. RESULTS:Serum IL-1β levels weresignificantlyhigher in FS patients (Median = 301.64 pg/ml) than in fever only controls (Median = 159.48 pg/ml) (P < 0.05). Additionally, NLRP3 protein levels of peripheral blood mononuclear cells (PBMC) were significantly higher in typical FS than in fever only controls (P < 0.05). Moreover, serum levels of IL-1β were significantly correlated with levels of NLRP3 protein (r = 0.787, P < 0.001). CONCLUSIONS:In this study, our results firstly indicated that NLRP3 protein was significantly up-regulated in the typical FS children compared in fever only controls. Increased NLRP3 can mediate IL-1β secretion that is responsible for the occurrence of FS.

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BACKGROUND & AIMS: PURPOSE:This post hoc analysis assessed the effects of adjunctive perampanel on myoclonic and absence seizure outcomes in patients (aged ≥12 years) with idiopathic generalized epilepsy (IGE) and generalized tonic-clonic seizures during the double-blind (up to 8 mg/day) and open-label extension (OLEx; up to 12 mg/day) phases of Study 332. METHODS:Patients experiencing myoclonic and/or absence seizures during study baseline were included. Assessments for myoclonic and absence seizures included: median percent change in seizure frequency, number of seizure days and seizure-free days (all per 28 days), 50 % and 75 % responder rates, seizure-freedom rates, seizure worsening, and monitoring of treatment-emergent adverse events (TEAEs). RESULTS:During the double-blind phase, myoclonic and/or absence seizures were reported in 47/163 and 60/163 patients, respectively. Median percent reductions in seizure frequency per 28 days from study baseline were 52.5% and 24.5% (myoclonic seizures) and 7.6 % and 41.2 % (absence seizures) for placebo and perampanel, respectively; seizure-freedom rates were 13.0 % and 16.7 % (myoclonic seizures) and 12.1 % and 22.2 % (absence seizures), respectively. During the OLEx phase, 46/138 and 52/138 patients experienced myoclonic and/or absence seizures, respectively. Responses during the double-blind phase were maintained during long-term (>104 weeks) adjunctive perampanel treatment. The frequency/type of TEAEs was consistent with the known safety profile of perampanel. CONCLUSION:In this post hoc analysis, adjunctive perampanel was not associated with any overall worsening of absence seizures. Further research is needed to investigate the effect of adjunctive perampanel in IGE patients with myoclonic and/or absence seizures.

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BACKGROUND & AIMS: :Systemic administration does not allow a clear differentiation between the anticonvulsant properties of GABAA (gamma-aminobutyric acid) modulators. For this reason, various GABAA modulators have previously been micro-infused into seizure controlling substrates (area tempestas, substantia nigra) in the rat brain as a screening method for potential systemic administration. The purpose of the present study was to examine the anticonvulsant impact of the GABAergic modulators muscimol, ethanol, and propofol (screened by micro-infusions) when each drug was combined with procyclidine and administered systemically. The results showed that all 3 combinations could effectively terminate soman-induced (100 microg/kg s.c.) seizures when administered 30-35 min after onset. Procyclidine and propofol were considered as the most relevant double regimen to replace a previous triple regimen (procyclidine, diazepam, pentobarbital) against soman-induced seizures. Additionally, it was shown that unilateral implantation of hippocampal electrodes resulted in increased resistance to aphagia/adipsia and neuropathology, but not to lethality following soman. Efficient pharmacological treatment of soman-induced seizures at an early stage (< 20 min) is crucial to avoid neuropathology and cognitive deficits.

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BACKGROUND & AIMS: :We have studied 342 patients who had their first seizures after the age of 60 years. The causes of seizures were identified in 305 patients (89%) with cerebrovascular disease accounting for 39%, head injury 21%, brain tumours 11%, metabolic disorders 7%, multifactorial aetiology 6%, and CNS infection 4%. The majority of patients (80%) had focal onset seizures that were secondarily generalized in 50%.

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BACKGROUND & AIMS: PURPOSE:To investigate spatial and metabolic changes associated with frontal lobe seizures. METHODS:Functional near-infrared spectroscopy combined with electroencephalography (EEG-fNIRS) recordings of patients with confirmed nonlesional refractory frontal lobe epilepsy (FLE). KEY FINDINGS:Eighteen seizures from nine patients (seven male, mean age 27 years, range 13-46 years) with drug-refractory FLE were captured during EEG-fNIRS recordings. All seizures were coupled with significant hemodynamic variations that were greater with electroclinical than with electrical seizures. fNIRS helped in the identification of seizures in three patients with more subtle ictal EEG abnormalities. Hemodynamic changes consisted of local increases in oxygenated (HbO) and total hemoglobin (HbT) but heterogeneous deoxygenated hemoglobin (HbR) behavior. Furthermore, rapid hemodynamic alterations were observed in the homologous contralateral region, even in the absence of obvious propagated epileptic activity. The extent of HbO activation adequately lateralized the epileptogenic side in the majority of patients. SIGNIFICANCE:EEG-fNIRS reveals complex spatial and metabolic changes during focal frontal lobe seizures. Further characterization of these changes could improve seizure detection, localization, and understanding of the impact of focal seizures.

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BACKGROUND & AIMS: :We describe two patients with psychogenic seizures of rare semiology. Both patients (a 23-year-old man and a 26-year-old woman) attended the emergency department because status epilepticus with myoclonic seizures had been diagnosed. Seizures were documented with video-electroencephalography. Semiology of seizures were brief myoclonia of both arms resulting in a short elevation of both arms without impairment of consciousness. Ictal EEG registration was without abnormal finding. Psychiatric diagnostic assessment suggested a dissociative disorder and mild depression, respectively. During psychiatric treatment seizures occurred only rarely within a 3-5 months follow-up. One should be aware that juvenile myoclonic epilepsy may be mimicked by psychogenic seizures

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BACKGROUND & AIMS: :The purpose of this study was to determine school nurses' knowledge of state and school district policies, their experience regarding the administration of rectal diazepam gel in the school, and the perceived benefits and barriers of providing this treatment. Four hundred nineteen nurses responded to a survey conducted during the National Association of School Nurses Annual Meeting. Seventy-one (18%) nurses surveyed had administered rectal diazepam gel in a school setting, while 54 (13%) nurses reported that either their state practice act or school district prohibited them from giving rectal medications in the school. Medication administration benefits, such as early intervention for treatment of acute seizure emergencies, were noted. Barriers were also identified, with lack of privacy as the most frequently listed. Scope of practice as it pertains to administering medication in the school and the extent to which delegation of duties can be used in the situation of administering rectal medication in a seizure emergency remain issues for school nurses.

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BACKGROUND & AIMS: :A number of neurotoxins derived from arthropod venoms are known to show highly selective effects on nervous tissue. These neurotoxins have been proved to be extremely useful tools to investigate either convulsive or anticonvulsive mechanisms in the nervous system. In the present work, intracerebroventricular injection of the crude venom from the spider Parawixia bistriata (Araneae, Araneidae) in rats induced convulsive limbic seizures (head and forelimb myoclonus, as well as rearing and falling). Neuroethological analysis showed that the limbic seizures induced by the venom were different from those induced by kainic acid. Intravenous injection of the same venom did not induce seizures, but the neuroethological analysis showed an intensification of grooming behavior similar to a displaced activity. In conclusion, our experiments point that crude venom of P. bistriata may contain convulsant neurotoxins probably acting in limbic system structures. The mechanism of action of these neurotoxins may be different from simple activation of glutamatergic kainate receptors, as evidenced by a comparative neuroethological analysis of seizures induced by either venom or kainic acid.

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BACKGROUND & AIMS: :We sought to investigate (1) differences in ictal duration between psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES), (2) the odds of being PNES when seizures last ≥5min, and (3) the value of ictal duration as a diagnostic test to differentiate PNES from ES. We retrospectively reviewed video-EEG recordings and tabulated ictal durations of all PNES and ES. We estimated the mean ictal durations of PNES and ES using linear mixed models. The odds of being PNES when seizures last ≥5min were estimated using logistic regression. We used receiver operating characteristics (ROC) curves to study the overall diagnostic accuracy of ictal duration in differentiating PNES from ES. We studied 441 ES and 341 PNES recorded from 138 patients. The mean ictal duration of PNES (148.7s, 95% CI: 115.2-191.8) was significantly longer (p<0.001) than that of ES (47.7s, 95% CI: 37.6-60.6). The odds of being PNES was about 24 times higher (Odds ratio: 23.8, 95% CI: 7.9-71.3) when the ictal duration was ≥5min. The ROC curve yielded an area under the curve of 0.80 (95% CI 0.73-0.88). Youden's index identified 123.5s as the optimal threshold to diagnose PNES with 65% sensitivity and 93% specificity. Our results indicate that ictal duration is a useful test to raise suspicion of PNES. When a seizure lasts ≥5min, it is 24 times more likely to be PNES with the potential risk of misdiagnosis as status epilepticus.

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BACKGROUND & AIMS: :Approaches to control epilepsy, one of the most important idiopathic brain disorders, are of great importance for public health. We have previously shown that in sympathetic neurons the neuronal isoform of the serum and glucocorticoid-regulated kinase (SGK1.1) increases the M-current, a well-known target for seizure control. The effect of SGK1.1 activation on kainate-induced seizures and neuronal excitability was studied in transgenic mice that express a permanently active form of the kinase, using electroencephalogram recordings and electrophysiological measurements in hippocampal brain slices. Our results demonstrate that SGK1.1 activation leads to reduced seizure severity and lower mortality rates following status epilepticus, in an M-current-dependent manner. EEG is characterized by reduced number, shorter duration, and early termination of kainate-induced seizures in the hippocampus and cortex. Hippocampal neurons show decreased excitability associated to increased M-current, without altering basal synaptic transmission or other neuronal properties. Altogether, our results reveal a novel and selective anticonvulsant pathway that promptly terminates seizures, suggesting that SGK1.1 activation can be a potent factor to secure the brain against permanent neuronal damage associated to epilepsy.

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BACKGROUND & AIMS: :The neurotransmitter glutamate plays a pivotal role in the development of the neuropathological sequelae following acute seizures. Our previous data proved the efficacy of the NMDA-receptor antagonists on the symptoms, survival and neuronal activation in the 4-aminopyridine- (4-AP) induced seizures. In this study, we examined the effects of two different doses of a non-competitive, selective, allosteric AMPA-receptor antagonist, GYKI 52466. GYKI 52466 was effective in prolonging the latency to generalised seizures and reduction of seizure mortality. However, the effects on neuronal c-fos expression and astrocyte swelling were complex. The 25mg/kg dose of GYKI 52466 was effective in reducing the c-fos immunoreactivity (IR) in the hippocampus only. In the neocortex the overall c-fos-IR cell counts were increased significantly. Investigation of the neocortical parvalbumin-containing interneuron population proved that GYKI 52466 decreased c-fos expression. The 50mg/kg dose of GYKI 52466 significantly reduced the c-fos-IR in the neo- and allocortex, not only in principal neurons, but also in the parvalbumin-positive interneurons. The GYKI 52466-pretreatment did not prevent the astrocyte swelling in the investigated cortical areas; thus we conclude that the AMPA-receptors have little if any involvement in the in the mediation of neuropathological alterations in acute convulsions.

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BACKGROUND & AIMS: PURPOSE OF REVIEW:Acute brain injury (ABI) is a broad category of pathologies, including traumatic brain injury, and is commonly complicated by seizures. Electroencephalogram (EEG) studies are used to detect seizures or other epileptiform patterns. This review seeks to clarify EEG findings relevant to ABI, explore practical barriers limiting EEG implementation, discuss strategies to leverage EEG monitoring in various clinical settings, and suggest an approach to utilize EEG for triage. RECENT FINDINGS:Current literature suggests there is an increased morbidity and mortality risk associated with seizures or patterns on the ictal-interictal continuum (IIC) due to ABI. Further, increased use of EEG is associated with better clinical outcomes. However, there are many logistical barriers to successful EEG implementation that prohibit its ubiquitous use. Solutions to these limitations include the use of rapid EEG systems, non-expert EEG analysis, machine learning algorithms, and the incorporation of EEG data into prognostic models.

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