Seizure Response Research Articles

NMDA Antagonists for Refractory Seizures

Refractory status epilepticus (RSE) poses significant challenge, with a variety of novel therapeutics employed. Our goal was to evaluate the effectiveness of N-methyl D-aspartate (NMDA) receptor antagonists in the control of RSE. We performed a systematic review of all the literature, with all articles pulled from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to September 2013), reference lists of relevant articles, and gray literature. Two reviewers independently identified all manuscripts pertaining to the administration of NMDA receptor antagonists in humans for the purpose of controlling refractory seizures. Secondary outcome of adverse NMDA antagonist effects and patient outcome was assessed. Two reviewers independently extracted data including population characteristics, treatment characteristics, and outcomes. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total of 759 citations. Twenty-three articles, 16 manuscripts, and seven meeting proceedings, were considered for the review with all utilizing ketamine for seizure control. Only three studies were prospective studies. Fifteen and nine studies pertained to adults and pediatrics, respectively. Across all studies, of the 110 adult patients described, ketamine was attributed to electroencephalogram seizure response in 56.5 %, with a 63.5 % response in the 52 pediatric patients described. Adverse events related to ketamine were rare. Outcomes were poorly documented in the majority of the studies. There currently exists Oxford level 4, GRADE C evidence to support the use of ketamine for refractory seizures in the adult and pediatric populations. Further prospective study of early ketamine administration is warranted.

Stress during first pregnancy increases seizure threshold in adult male offspring.

Stress induces many homeostatic aberrations which are followed by lifelong allostatic responses. Epilepsy is developed or influenced by different environmental factors, i.e. prenatal stress which makes many contradictory developmental changes in seizure threshold and intensity. We investigated the potential seizure response of the rat offspring to prenatal stress; the stress which was applied to their mothers. Nine day heterogeneous sequential stress (HSS) model was used before and during the first and before the second pregnancy. The kindling was induced using 13 IP injections of pentylenetetrazol (PTZ) every 48 hr to adult male Wistar rat's offspring. The results of the present study demonstrated that, before pregnancy stress decreased the rate of kindling (P<0.05) in the offspring, while stress which was applied during pregnancy completely prevented kindling (P <0.001). Further, their convulsive latency was increased and tonic clonic seizure duration was decreased. In contrast, previous pregnancy and between pregnancies stress could not change kindling process. Although maternal separation stress did not change kindling development, it could increase convulsive intensities by elongating the duration of seizures (P<0.05) and reducing convulsion latency (P <0.05). It is concluded that stress detrimental effects could be prevented by stress which was applied around first pregnancy; however this beneficial effect is weakened by before second pregnancy stress.

Gene Expression Profiling of a Hypoxic Seizure Model of Epilepsy Suggests a Role for mTOR and Wnt Signaling in Epileptogenesis

Microarray profiling was used to investigate gene expression in the hypoxic seizure model of acquired epilepsy in the rat, with the aim of characterizing functional pathways which are persistently activated or repressed during epileptogenesis. Hippocampal and cortical tissues were transcriptionally profiled over a one week period following an initial series of seizures induced by mild hypoxia at post-natal day 10 (P10), and the gene expression data was then analyzed with a focus on gene set enrichment analysis, an approach which emphasizes regulation of entire pathways rather than of individual genes. Animals were subjected to one of three conditions: a control with no hypoxia, hypoxic seizures, and hypoxic seizures followed by treatment with the AMPAR antagonist NBQX, a compound currently proposed to be a modulator of epileptogenesis. While temporal gene expression in the control samples was found to be consistent with known processes of neuronal maturation in the rat for the given time window, the hypoxic seizure response was found to be enriched for components of the PI3K/mTOR and Wnt signaling pathways, alongside gene sets representative of glutamatergic, synaptic and axonal processes, perhaps regulated as a downstream consequence of activation of these pathways. Wnt signaling components were also found enriched in the more specifically epileptogenic NBQX-responsive gene set. While activation of the mTOR pathway is consistent with its known role in epileptogenesis and strengthens the case for mTOR or PI3K pathway inhibitors as potential anti-epileptogenic drugs, investigation of the role of Wnt signaling and the effect of appropriate inhibitors might offer a parallel avenue of research toward anti-epileptogenic treatment of epilepsy.

Scn8a voltage-gated sodium channel mutation alters seizure and anxiety responses to acute stress

Stress is known to trigger seizures in patients with epilepsy, highlighting the physiological stress response as a possible therapeutic target for epilepsy treatment. Nevertheless, little is currently known about how a genetic predisposition to epilepsy interacts with the stress response to influence seizure outcome. To address this question, we examined the effect of acute stress on seizure outcome in mice with mutations in the voltage-gated sodium channel (VGSC) gene Scn8a. Scn8a mutants display spontaneous spike-wave discharges (SWDs) characteristic of absence epilepsy. We saw that the baseline frequency of SWDs in Scn8a mutants correlates closely with the diurnal activity of the hypothalamic-pituitary-adrenal (HPA) axis, with a peak in seizure activity occurring at around the same time as the peak in corticosterone (1700-1900h). A 20-min acute restraint stress administered in the morning increases the frequency of spontaneous SWDs immediately following the stressor. Seizure frequency then returns to baseline levels within 3h after stressor exposure, but the subsequent evening peak in seizure frequency is delayed and broadened, changes that persist into the next evening and are accompanied by long-lasting changes in HPA axis activity. Scn8a mutants also show increased anxiety-like behavior in mildly stressful situations. A 20-min acute restraint stress can also increase the severity and duration of chemically induced seizures in Scn8a mutants, changes that differ from wild-type littermates. Overall, our data show that a voltage-gated sodium channel mutation can alter the behavioral response to stress and can interact with the stress response to alter seizure outcome.

Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy: A pilot study

PurposeVerapamil, a voltage-gated calcium channel blocker, has been occasionally reported to have some effect on reducing seizure frequency in drug-resistant epilepsy or status epilepticus. We aimed to investigate the efficacy of verapamil as add-on treatment in children with drug-resistant epilepsy. MethodsSeven children with drug-resistant structural-metabolic, unknown or genetic (e.g., Dravet syndrome [DS]) epilepsy received verapamil as an add-on drug to baseline antiepileptic therapy. Verapamil was slowly introduced at the dosage of 1mg/kg/day and titrated up to 1.5mg/kg/day. After completing the titration period, patients entered a 14-month maintenance period and were followed up at 3, 8, and 14 months. Heart monitoring was performed at baseline and at each follow-up. The primary outcome measure was the response of seizures to verapamil. ResultsThree subjects with genetically determined DS showed a partial (reduction of 50–99%) response for all types of seizures. A patient with DS without known mutation showed a partial control of all types of seizures in the first 13 months; then seizures worsened and verapamil was suspended. Two patients with structural epilepsy and one with Lennox–Gastaut syndrome showed no improvement. Any side effects were recorded. ConclusionsAdd-on treatment with verapamil seems to have some effect in controlling seizures in patients with genetically determined DS. Our observations justify further research on the relationship between calcium channels, calcium channel blockers, and channelopathies.

Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study

Little information is available regarding the effect of conventional radiotherapy on glioma-related seizures. In this retrospective study, we analyzed the seizure response and outcome following conventional radiotherapy in a cohort of 43 patients with glioma (33 grade II, 10 grade III) and medically intractable epilepsy. At 3 months after radiotherapy, seizure reduction was significant (≥ 50% reduction of frequency compared with baseline) in 31/43 patients (72%) of the whole series and in 25/33 patients (76%) with grade II gliomas, whereas at 12 months seizure reduction was significant in 26/34 (76%) and in 19/25 (76%) patients, respectively. Seizure reduction was observed more often among patients displaying an objective tumor response on MRI, but patients with no change on MRI also had a significant seizure reduction. Seizure freedom (Engel class I) was achieved at 12 months in 32% of all patients and in 38% of patients with grade II tumors. Timing of radiotherapy and duration of seizures prior to radiotherapy were significantly associated with seizure reduction. This study showed that a high proportion of patients with medically intractable epilepsy from diffuse gliomas derive a significant and durable benefit from radiotherapy in terms of epilepsy control and that this positive effect is not strictly associated with tumor shrinkage as shown on MRI. Radiotherapy at tumor progression seems as effective as early radiotherapy after surgery. Prospective studies must confirm and better characterize the response to radiotherapy.

Efficacy of vagus nerve stimulation as a treatment for medically intractable epilepsy in brain tumor patients. A case-controlled study using the VNS therapy Patient Outcome Registry

PurposeVagus nerve stimulation (VNS) therapy is a procedure to control seizure frequency in patients with medically intractable epilepsy. However, there is no data on efficacy in the subset of these patients with brain tumors. The purpose of this study is to evaluate the efficacy of VNS therapy in patients with brain tumor-associated medically intractable epilepsy. MethodsData from the VNS therapy Patient Outcome Registry, maintained by the manufacturer of the device, Cyberonics Inc. (Houston, TX, USA), was queried to characterize the response of patients in whom a brain tumor was listed as the etiology of epilepsy. A case–control analysis was implemented and patient outcome was measured by Engel classification, median seizure response and responder rate (≥50% seizure reduction) using t-tests and chi-squared tests. ResultsIn 107 patients with an epilepsy etiology related to a brain tumor, seizure reduction was 45% at 3 months and 79% at 24 months with a responder rate of 48% at 3 months and 79% at 24 months. There was no statistical difference in seizure reduction compared with 326 case–control patients from the registry without brain tumors. There was no significant difference in anti-epileptic drug (AED) usage from baseline to 24 months post implant in either group. ConclusionsVNS therapy is equally effective in patients who suffer seizures secondary to brain tumors as in patients without history of a brain tumor. VNS therapy is a viable treatment option for patients with brain tumor associated medically intractable epilepsy, assuming cytoreductive and other adjuvant therapies have been fully explored.

Trans-middle temporal gyrus selective amygdalohippocampectomy for medically intractable mesial temporal lobe epilepsy in adults: Seizure response rates, complications, and neuropsychological outcomes

ObjectiveSelective amygdalohippocampectomy (AHC) has evolved to encompass a variety of techniques to resect the mesial temporal lobe. To date, there have been few large-scale evaluations of trans-middle temporal gyrus selective AHC. The authors examine a large series of patients who have undergone the trans-middle temporal gyrus AHC and assess its clinical and neuropsychological impact. MethodsA series of 76 adult patients underwent selective AHC via the trans-middle temporal gyrus approach over a 10-year period, 19 of whom underwent pre- and postoperative neuropsychological evaluations. ResultsFavorable seizure response rates were achieved (92% Engel class I or II), with very low surgical morbidity and no mortality. Postoperative neuropsychological assessment revealed a decline in verbal memory for the left AHC group. No postoperative memory decline was identified for the right AHC group, but rather some improvements were noted within this group. ConclusionsThe trans-middle temporal gyrus selective AHC is a safe and effective choice for management of medically refractory epilepsy in adults.

The Auxiliary Subunit KChIP2 Is an Essential Regulator of Homeostatic Excitability

The necessity for, or redundancy of, distinctive KChIP proteins is not known. Deletion of KChIP2 leads to increased susceptibility to epilepsy and to a reduction in IA and increased excitability in pyramidal hippocampal neurons. KChIP2 is essential for homeostasis in hippocampal neurons. Mutations in K(A) channel auxiliary subunits may be loci for epilepsy. The somatodendritic IA (A-type) K(+) current underlies neuronal excitability, and loss of IA has been associated with the development of epilepsy. Whether any one of the four auxiliary potassium channel interacting proteins (KChIPs), KChIP1-KChIP4, in specific neuronal populations is critical for IA is not known. Here we show that KChIP2, which is abundantly expressed in hippocampal pyramidal cells, is essential for IA regulation in hippocampal neurons and that deletion of Kchip2 affects susceptibility to limbic seizures. The specific effects of Kchip2 deletion on IA recorded from isolated hippocampal pyramidal neurons were a reduction in amplitude and shift in the V½ for steady-state inactivation to hyperpolarized potentials when compared with WT neurons. Consistent with the relative loss of IA, hippocampal neurons from Kchip2(-/-) mice showed increased excitability. WT cultured neurons fired only occasional single action potentials, but the average spontaneous firing rate (spikes/s) was almost 10-fold greater in Kchip2(-/-) neurons. In slice preparations, spontaneous firing was detected in CA1 pyramidal neurons from Kchip2(-/-) mice but not from WT. Additionally, when seizures were induced by kindling, the number of stimulations required to evoke an initial class 4 or 5 seizure was decreased, and the average duration of electrographic seizures was longer in Kchip2(-/-) mice compared with WT controls. Together, these data demonstrate that the KChIP2 is essential for physiologic IA modulation and homeostatic stability and that there is a lack of functional redundancy among the different KChIPs in hippocampal neurons.

Efficacy of vagus nerve stimulation in brain tumor–associated intractable epilepsy and the importance of tumor stability

Vagus nerve stimulation (VNS) is a viable option for patients with medically intractable epilepsy. However, there are no studies examining its effect on individuals with brain tumor-associated intractable epilepsy. This study aims to evaluate the efficacy of VNS in patients with brain tumor-associated medically intractable epilepsy. Epilepsy surgery databases at 2 separate epilepsy centers were reviewed to identify patients in whom a VNS device was placed for tumor-related intractable epilepsy between January 1999 and December 2011. Preoperative and postoperative seizure frequency and type as well as antiepileptic drug (AED) regimens and degree of tumor progression were evaluated. Statistical analysis was performed using odds ratios and t-tests to examine efficacy. Sixteen patients were included in the study. Eight patients (50%) had an improved outcome (Engel Class I, II, or III) with an average follow-up of 39.6 months. The mean reduction in seizure frequency was 41.7% (p = 0.002). There was no significant change in AED regimens. Seizure frequency decreased by 10.9% in patients with progressing tumors and by 65.6% in patients with stable tumors (p = 0.008). Vagus nerve stimulation therapy in individuals with brain tumor-associated medically intractable epilepsy was shown to be comparably effective in regard to seizure reduction and response rates to the general population of VNS therapy patients. Outcomes were better in patients with stable as opposed to progressing tumors. The authors' findings support the recommendation of VNS therapy in patients with brain tumor-associated intractable epilepsy, especially in cases in which imminent tumor progression is not expected. Vagus nerve stimulation may not be indicated in more malignant tumors.

Effects of Low-Frequency Hippocampal Stimulation on Gamma-Amino Butyric Acid Type B Receptor Expression in Pharmacoresistant Amygdaloid Kindling Epileptic Rats

To observe the effect of low-frequency hippocampal stimulation on gamma-amino butyric acid type B (GABA-B) receptor expression in hippocampus pharmacoresistant epileptic rats. Sixteen pharmacoresistant epileptic rats were selected by testing their seizure response to phenytoin and phenobarbital, and they were randomly divided into a pharmacoresistant control group (PRC group, eight rats) and a pharmacoresistant stimulation group (PRS group, eight rats). Another 16 pharmacosensitive epileptic rats were served as control, also divided randomly into a pharmacosensitive control group (PSC group) and a pharmacosensitive stimulation group (PSS group). A stimulation electrode was implanted into the rats' hippocampus in the four groups. Low-frequency hippocampal stimulation was administered twice per day for two weeks. Following these weeks of stimulation, GABA-B receptor-positive neurons were counted and the gray values of GABA-B receptor expression in the rats' hippocampal tissues were measured. The amygdale stimulus-induced epileptic seizures were decreased significantly in the PRS group compared with the PRC group. The parameters of the amygdale after discharge also were improved after hippocampal stimulation. Simultaneously, the GABA-B receptor-positive neurons increased and the GABA-B expression gray values decreased markedly in the PRS group compared with the PRC group. The same phenomenon also was observed between the PSS group and the PSC group. However, no significant difference was found in the GABA-B receptor-positive neurons and the gray values of GABA-B between the PRS group and the PSC group. The low-frequency hippocampal stimulation may inhibit the amygdale stimulus-induced epileptic seizures and the after discharges. The antiepileptic effects of the hippocampal stimulation may be achieved partly by increasing the expression of the GABA-B receptor.

Epilepsy in Mowat–Wilson syndrome: Delineation of the electroclinical phenotype

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.

New-onset status epilepticus and cluster seizures in the elderly

We evaluated the frequency, therapeutic response and predictors of status epilepticus (SE) and cluster seizures among elderly people. Patients over 60years old with epilepsy (n=201; age, 68.0±7.5years) were prospectively recruited. Among them, 64 patients (32%) who presented with new-onset cluster attacks and/or SE formed the study group. All underwent evaluation with electroencephalography (EEG) and CT scans. The mean duration of SE and cluster seizures at admission was 14.9±53.7hours. Cluster seizures were observed in 53 (26.4%) and SE in 34 (17%) elderly patients with seizures (n=201). The types of SE were: generalized convulsive (23 patients), epilepsia partialis continua (eight patients), non-convulsive (two patients) and myoclonic (one patient). The types of epilepsy syndrome included were: acute symptomatic (37 patients; 57.8%), cryptogenic (15 patients; 23.4%) and remote symptomatic (12 patients; 18.8%). Interictal EEG was abnormal in 79.7% of patients with critical presentation compared to 53.3% of patients without critical presentation. Epileptiform activity was observed in 46.9% of patients with SE and/or cluster seizures compared to 27.0% without SE and/or cluster seizures (p=0.001). The neuroimaging differences between the two groups were the absence of white-matter changes on CT scan in those with, compared to those without, SE and/or cluster seizures (28.1% compared to 41.6%, p=0.06). The risk factors for SE and/or cluster seizures were: acute symptomatic seizures, simple partial seizures, a higher number of seizures, lower Glasgow coma scale (GCS) score and an absence of white-matter changes on CT scan. After multivariate analysis, lower GCS score (p=0.01; odds ratio [OR]=0.82) and a higher number of seizures (p=0.03; OR=1.03) significantly predicted the occurrence of SE and/or cluster seizures. Seizures were controlled with two antiepileptic drugs in 70.6%. To conclude, SE and/or cluster seizures are common (32%) among elderly patients with epilepsy. Early and aggressive treatment is effective in the majority.

Differential seizure response in two models of cortical heterotopia

Malformations of cortical development (MCD) are linked to epilepsy in humans. MCD encompass a broad spectrum of malformations, which occur as the principal pathology or a secondary disruption. Recently, Rosen et al. (2012) reported that BXD29-Trl4lps−2J/J mice have subcortical nodular heterotopias with partial agenesis of the corpus callosum (p-ACC). Additionally Ramos et al. (2008) demonstrated that C57BL/10J mice exhibit cortical heterotopias with no additional cortical abnormalities. We examined the seizure susceptibility of these mice to determine if the presence (BXD29-Trl4lps−2J/J) or absence (C57BL/10J) of p-ACC, in strains with MCD, confers a differential response to chemi-convulsive treatment. Our results indicate that C57BL/10J mice with layer I heterotopia are more susceptible, whereas BXD29-Trl4lps−2J/J mice with more severe subcortical nodular heterotopia and p-ACC are more resistant to seizure behavior induced by pentylenetetrazole. These data suggest that p-ACC may confer seizure resistance in models of MCD.

Rufinamide in Children with Refractory Epilepsy: Pharmacokinetics, Efficacy, and Safety

We examined the influence of age and type of concomitant antiepileptic drugs (AEDs) on the pharmacokinetics of rufinamide (RUF) as well as its efficacy and safety in 51 children with refractory epilepsy. In a retrospective noninterventional survey, dose-to-concentration ratios of RUF and concomitant AEDs were calculated: the weight-normalized dose (mg/kg/d) divided by the steady-state trough plasma drug level, which was used as a measure of clearance. During treatment with RUF concomitantly with valproic acid (VPA) young children, aged 0 to 4.9 years, had a low clearance of RUF, which did not differ from older children. If not on VPA but on enzyme inducers, young children had a threefold higher clearance of RUF than the older ones. In young children not on VPA, those on enzyme inducers had 1.7-fold higher clearance than those on nonenzyme inducers. In children neither on VPA nor on enzyme inducers, RUF clearance was age-dependent with higher clearance in younger children. Adding RUF did not change the pharmacokinetics of concomitantly used AEDs. Seizure response after 2 to 3 months on RUF treatment was found in 12 of 51 children (23.5%), at mean plasma level of 36.9 ± 22.0 µmol/L. Adverse events were reported in 41% of the patients of which fatigue was most frequent (24%).

Brain tumor–associated seizures

Seizures are among the most important clinical issues in patients with brain tumors. About half of them will experience at least one seizure during the course of the disease, and seizures often herald the presence of a yet unknown cerebral neoplasm. Seizure incidence, frequency, and response to treatment are highly variable and depend on tumor type, grade, and localization, among other factors.1 The epileptogenic mechanism of tumor-associated seizures (TAS) is likely multifactorial and complex, and still poorly understood,2 including such factors as …

Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up

BackgroundThe seizure response to the addition of a previously unused antiepileptic drug in a cohort of 155 people with refractory epilepsy was previously reported after a median of 18 months...

BAD-Dependent Regulation of Fuel Metabolism and KATP Channel Activity Confers Resistance to Epileptic Seizures

Neuronal excitation can be substantially modulated by alterations in metabolism, as evident from the anticonvulsant effect of diets that reduce glucose utilization and promote ketone body metabolism. We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phosphoregulation of BAD and are independent of its apoptotic function. BAD modifications that reduce glucose metabolism produce a marked increase in the activity of metabolically sensitive K(ATP) channels in neurons, as well as resistance to behavioral and electrographic seizures in vivo. Seizure resistance is reversed by genetic ablation of the K(ATP) channel, implicating the BAD-K(ATP) axis in metabolic control of neuronal excitation and seizure responses.

Exposure to prenatal stress enhances the development of seizures in young rats

A febrile seizure is a neurological disorder that occurs following an infection that results in a rapid rise in body temperature. It commonly affects 3-5% of children between the ages of 3 months and 5 years. Interleukin-1 beta IL-1β a pro-inflammatory cytokine has been suggested to play a role in the manifestation of febrile seizures. There is evidence suggesting that neurological disorders can be exacerbated in an offspring that was exposed to stress prenatally. The aim of our study was therefore to investigate whether febrile seizures are exacerbated in the offspring of rats that were prenatally stressed. The offspring of pregnant Sprague-Dawley dams were used in the study. Prenatal stress consisted of exposing the pregnant dams to 45 min of restraint, 3 times per day with 3 h intervals in-between, for 7 days starting on gestational day 14 (GND14). On postnatal day (PND) 14, the pups were injected with lipopolysaccharide (LPS, 200 μg/kg, i.p.) followed 2.5 h later by an i.p. injection of kainic acid (KA, 1.75 mg/kg). All the animals were decapitated on PND 21. Trunk blood was collected to detect plasma interleukin-1beta (IL-1β) levels in the various groups. Our data showed that i.p. injections of LPS followed by KA led to the development of seizure activity that was associated with increased plasma IL-1β levels. Prior exposure to prenatal stress resulted in the development of advanced stages of seizure development, leading to an exaggerated seizure response. Prenatal stress alone also led to elevated plasma IL-1β levels, while previously stressed animals receiving LPS and KA yielded the highest plasma levels of IL-1β levels. Our data therefore shows that IL-1β levels may play an important role in the development of febrile seizures.

The response score is a tool that measures patients’ response to ketogenic therapy

BackgroundKetogenic Therapy (KT) is a high fat, low carbohydrate, adequate protein diet used to treat patients with intractable epilepsy with the goal of eliminating seizures and the need for anti‐epileptic drugs (AEDs).ObjectiveTo develop a tool to measure seizure response and need for AEDs during treatment.MethodsRanking numbers are given to five seizure parameters (frequency, type, severity, length, and characteristics), and summed to give the seizure point total (SPT). The seizure score (SS) is the daily SPT as a percent change from the baseline SPT. The medication load (ML) is the prescribed AED dosage divided by the minimum AED dosage. The medication score (MS) is the daily ML as a percent change from the baseline ML. The response score (RS) is the average of the daily SS and MS.ResultsIn our practice we have observed that SS and MS may both decrease, only SS may decrease, or neither parameter may decrease during treatment. The SS, MS, and RS for three patients at the end of the first year on KT are presented in the table below.ConclusionThe RS presents an overall change and can be used to stratify patients into responders and non‐responders to KT.Supported in part by the National Institutes of Health (NIH) and National Center for Research Resources (NCRR) CTSA grant 1UL1RR029890