Non-refractory Epilepsy Research Articles

Evaluation of GFAP, S100B, and UCHL-1 Levels in Children With Refractory Epilepsy.

A number of biomarkers are used to evaluate the duration of the epileptic seizure and the interictal period following neuronal injury. Invasive diagnostic methods are increasingly being replaced by peripheral or minimally invasive biomarkers that give results faster and are more secure. We aimed to evaluate serum glial fibrillary acidic protein (GFAP), S100B, and ubiquitin C-terminal hydrolase (UCHL-1) levels in children with epilepsy. Our study included 3 groups: a nonrefractory epilepsy group, a refractory epilepsy group, and a control group. The GFAP, S100B, and UCHL-1 levels in serum samples collected 2-24 hours after the last seizure were analyzed using enzyme-linked immunosorbent assays. A total of 69 children participated in the study, with 35 participants in the refractory epilepsy group, 18 in the nonrefractory epilepsy group, and 16 in the control group. The GFAP values in the refractory (25.4 ng/mL) and nonrefractory (26.1 ng/mL) epilepsy groups were found to be statistically significantly higher than those in the control group (17.9 ng/mL; P = .001). The S100B values were found to be significantly higher in the refractory epilepsy group (34.13 pg/mL) than in both the control group and the nonrefractory epilepsy group (28.05 pg/mL; P = .028). No significant differences were observed in the UCHL-1 levels between the 3 groups. We conclude that the observed differences may be due to the increased expression of S100B and GFAP caused by increased and repetitive neuronal damage in refractory epilepsies compared with nonrefractory epilepsies.

Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study.

In this prospective observational study, we aimed to investigate the serum levels of sirtuin (SIRT)3 in epilepsy patients and its association with the severity of the disease. This prospective observational study included 203 patients with symptomatic epilepsy and 100 healthy controls who visited our hospital from November 2019 to November 2022. The severity of the disease in epilepsy patients was assessed using the National Hospital Seizure Severity Scale (NHS3). We used enzyme-linked immunosorbent assay to measure the serum levels of SIRT3, interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha, and C-reactive protein in all patients. In addition, the cognitive function of all study participants was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment (MOCA). All data were analyzed using SPSS 25.0 software. The MOCA scores of the epilepsy patients were significantly lower compared to the healthy volunteers (P < 0.05). The serum SIRT3 levels were decreased significantly in patients with refractory epilepsy (183.16 ± 17.22 pg/mL) compared to non-refractory epilepsy patients (199.00 ± 18.68 pg/mL). In addition, serum SIRT3 levels were negatively correlated with the inflammatory factors IL-6 (Pearson's correlation -0.221, P = 0.002) and NHS score (Pearson's correlation -0.272, P < 0.001) of epilepsy patients, while positively correlated with MOCA scores (Pearson's correlation 0.166, P = 0.018). Furthermore, the receiver operating characteristic curve demonstrated that serum SIRT3 could be used to diagnose epilepsy, as well as refractory epilepsy. Finally, logistic regression analysis showed that SIRT3 (OR = 1.028, 95%CI: 1.003-1.054, P = 0.028), IL-6 (OR = 0.666, 95%CI: 0.554-0.800, P < 0.001), IL-1β (OR = 0.750, 95%CI: 0.630-0.894, P = 0.001), and NHS3 (OR = 0.555, 95%CI: 0.435-0.706, P < 0.001) were risk factors for refractory epilepsy. In conclusion, our findings demonstrated that serum SIRT3 levels were significantly decreased in epilepsy patients and further decreased in patients with refractory epilepsy. This study might provide new therapeutic targets and comprehensive treatment strategies for epilepsy patients.

Biochemical risk factors associated with refractory epilepsy: alpha synuclein and adenosine deaminase

Abstract Background Epilepsy is a common chronic neurological disorder affecting all age groups. A significant portion of children with epilepsy develop drug-resistant seizures. These children are at risk of cognitive and behavioral comorbidities and death. Some clinical features provide important information about the prognosis of epilepsy. However, currently, there is no objective biochemical indicator associated with refractory epilepsy. This study aimed to determine whether serum alpha-synuclein (αS), pglycoprotein (P-gp), and adenosine deaminase activity (ADA) were biochemical risk factors for refractory epilepsy. Methods The cross-sectional study included patients diagnosed with refractory epilepsy (n=32), non-refractory epilepsy (n=35) and 20 healthy children under the age of 18 who applied to the Pediatric Neurology outpatient clinic. In the serum samples, αS and P-gp were analyzed by ELISA and ADA activity was analyzed by spectrophotometric method. ROC analysis was applied and the area under the curve (AUC) was calculated to define cut-off values in distinguishing refractory epilepsy patients from non-refractory epilepsy patients. Binary logistic regression analysis was performed to define risk factors associated with resistance in patients with epilepsy. Results Children with epilepsy whose ADA activity and αS values were higher than the determined cut-off values had 10-fold and 5.3-fold increased risk of refractory epilepsy, respectively. Conclusions αS and ADA activity can be used as biochemical risk factors for refractory epilepsy. However, these results need to be confirmed by prospective studies with many patients.

Understanding Health Care Provider Burnout When Caring for Patients With Refractory Epilepsy in the United States.

Among health care providers (HCPs), neurologists have one of the highest rates of burnout in the United States, compromising the quality and accessibility of patient care. Patients with refractory epilepsy are especially challenging to treat. This study aims to understand the burnout level in neurologists treating patients with refractory epilepsy and identify key contributing factors. US board-certified pediatric/adult neurologists who devote ≥50% of their time to clinical practice and treat ≥10 unique patients with refractory epilepsy annually were invited to take a noninterventional quantitative survey, designed to capture key elements of the HCP's background, burnout level, current practice, burden domains, and satisfaction with current antiseizure medications (ASMs). Burnout in 3 domains (emotional exhaustion, depersonalization, and personal accomplishment) was assessed by the validated Maslach Burnout Inventory-Human Services Survey. From March 11, 2022, to April 10, 2022, a total of 138 neurology-specialist HCPs participated in the survey, divided between adult epileptologists (n = 44), adult neurologists (n = 41), pediatric epileptologists (n = 36), and pediatric neurologists (n = 17). Of participating HCPs, 61% experienced at least some burnout (≥1 of 3 burnout domains categorized as high), and 4% experienced high burnout (3 of 3 burnout domains categorized as high). High burnout levels were driven by high pediatric and inpatient caseloads and unexpected pediatric patient reluctance to transition to adult care. HCPs with high burnout had a higher yearly caseload of patients with refractory epilepsy. Most HCPs (approximately 90%) indicated that patients with refractory epilepsy were more difficult to manage than those with nonrefractory epilepsy. The proportion of HCPs satisfied or extremely satisfied with ASMs was lower for patients with refractory epilepsy (20%) than that for patients with nonrefractory epilepsy (73%). Dissatisfaction was mostly due to workload and latency of the insurance approval process, out-of-pocket costs, and poor efficacy, safety, and tolerability. For 32% of HCPs, stopping practicing or moving to another practice within 5 years was probable or very probable. Some burnout is common among HCPs who treat patients with refractory epilepsy. However, management of refractory epilepsy is challenging, and satisfaction with available ASMs is low. Thus, addressing these contributing factors may help to alleviate HCP burnout.

1275 Machine Learning for Outcome Prediction in Epilepsy Surgery: A Systematic Review

Abstract Aim A third of epilepsy patients suffer from medically refractory seizures. In patients eligible for surgical treatment, seizure freedom rates remain variable. Machine learning (ML) utilises large datasets to detect patterns to make predictions. We systematically review studies employing ML models for prediction of outcome following resective epilepsy surgery to evaluate their efficacy, applicability and value in determining surgical candidacy. Method MEDLINE, Cochrane and EMBASE databases were searched for literature published between 2010 – 2020 according to PRISMA guidance. Non-refractory epilepsy, non-clinical outcome prediction, or non-human studies were excluded. Clinical and demographic data, ML features, discrimination and prediction accuracy metrics were extracted. Results 15 studies were included. Median cohort size was 49 (range 16 – 4211). Heterogeneous input data sources were utilised: MRI (n = 10) , electrophysiology (n = 4), PET (n = 2), clinical data (n = 2), and neuropsychological testing (n = 1). The most common ML model used was support vector machines (n = 7). All studies had good discrimination (AUC &amp;gt; 0.70, range: 0.79 [95% CI NR] - 0.94 [95% CI 0.92 – 0.96]), and good prediction accuracy (&amp;gt; 0.70, range: 0.76 [95% CI NR] – 0.95 [95% CI NR]). Limitations included small sample sizes, limited external validation and lack of comparison with clinician-predicted outcomes. Conclusions Machine Learning for outcome prediction could enhance clinical decision-making for surgical candidacy in epilepsy, and lead to improved precision medicine delivery. Outcome reporting remains inconsistent, and further work is required to externally validate such models to implement these to large-scale clinical populations.

Fiber ball white matter modeling in focal epilepsy.

Multicompartment diffusion magnetic resonance imaging (MRI) approaches are increasingly being applied to estimate intra‐axonal and extra‐axonal diffusion characteristics in the human brain. Fiber ball imaging (FBI) and its extension fiber ball white matter modeling (FBWM) are such recently described multicompartment approaches. However, these particular approaches have yet to be applied in clinical cohorts. The modeling of several diffusion parameters with interpretable biological meaning may offer the development of new, noninvasive biomarkers of pharmacoresistance in epilepsy. In the present study, we used FBI and FBWM to evaluate intra‐axonal and extra‐axonal diffusion properties of white matter tracts in patients with longstanding focal epilepsy. FBI/FBWM diffusion parameters were calculated along the length of 50 white matter tract bundles and statistically compared between patients with refractory epilepsy, nonrefractory epilepsy and controls. We report that patients with chronic epilepsy had a widespread distribution of extra‐axonal diffusivity relative to controls, particularly in circumscribed regions along white matter tracts projecting to cerebral cortex from thalamic, striatal, brainstem, and peduncular regions. Patients with refractory epilepsy had significantly greater markers of extra‐axonal diffusivity compared to those with nonrefractory epilepsy. The extra‐axonal diffusivity alterations in patients with epilepsy observed in the present study could be markers of neuroinflammatory processes or a reflection of reduced axonal density, both of which have been histologically demonstrated in focal epilepsy. FBI is a clinically feasible MRI approach that provides the basis for more interpretive conclusions about the microstructural environment of the brain and may represent a unique biomarker of pharmacoresistance in epilepsy.

Altered ANRIL Methylation in Epileptic Patients.

Long non-coding RNAs (lncRNAs) have regulatory roles in several aspects of cellular physiology. Recent studies have also revealed their role in neuronal differentiation and the pathophysiology of neurologic disorders such as epilepsy. We have recently reported altered expression of a number of lncRNAs in the peripheral blood of epileptic patients in association with their response to antiepileptic drugs. One the most significantly altered lncRNAs in epileptic patients is the antisense non-coding RNA in the INK4 locus (ANRIL), whose expression has been found to be higher in both refractory and non-refractory groups compared with controls. In the current study, we aimed to identify the methylation status of this lncRNA to suggest a potential mechanism for deregulated ANRIL expression. Thus, we assessed the methylation status of the ANRIL promoter in 40 patients with refractory epilepsy, 40 patients with non-refractory epilepsy and 40 normal controls using the high-resolution melting (HRM) method. The HRM results showed hypomethylation of the ANRIL promoter region in both refractory epilepsy and non-refractory epilepsy patients compared with normal controls. This methylation pattern was consistent with the recently reported upregulation of this lncRNA in patients with epilepsy. Thus, we suggest altered methylation of the ANRIL promoter as a potential cause of its aberrant expression in peripheral blood of epileptic patients.

Diminished toll-like receptor response in febrile infection-related epilepsy syndrome (FIRES)

BackgroundDefective human TLR3 signaling causes recurrent and refractory herpes simplex encephalitis/encephalopathy. Children with febrile infection-related epilepsy syndrome with refractory seizures may have defective TLR responses. MethodsChildren with febrile infection-related epilepsy syndrome were enrolled in this study to evaluate TLR1-9 responses (IL-6, IL-8, IL-12p40, INF-α, INF-γ, and TNF-α) in their peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MDDCs), compared to those with febrile seizures and non-refractory epilepsy with/without underlying encephalitis/encephalopathy. ResultsAdenovirus and enterovirus were found in throat cultures of enrolled patients (2–13 years) as well as serologic IgM elevation of mycoplasma pneumonia and herpes simplex virus, although neither detectable pathogens nor anti-neural autoantibodies in the CSF could be noted. Their PBMCs and MDDCs trended to have impaired TLR responses and significantly lower in cytokine profiles of TLR3, TLR4, TLR7/8, and TLR9 responses but not other TLRs despite normal TLR expressions and normal candidate genes for defective TLR3 signaling. They also had decreased naïve T and T regulatory cells, and weakened phagocytosis. ConclusionChildren with febrile infection-related epilepsy syndrome (FIRES) could have impaired TLR3, TLR4, TLR7/8, and TLR9 responses possibly relating to their weakened phagocytosis and decreased T regulatory cells.

Localization of cerebral hypoperfusion in dogs with refractory and non-refractory epilepsy using [99mTc] ethyl cysteinate dimer and single photon emission computed tomography.

To evaluate the localization of functional deficit area in epileptogenic zones of the brain in seven refractory and seven non-refractory epilepsy dogs using technetium 99m labeled with ethyl cysteinate dimer and interictal single photon emission computed tomography [99mTc-ECD SPECT] co-registration with Magnetic Resonance Imaging (MRI). Regions showing perfusion deficits in the SPECT images were analyzed by using the standard semiquantitative evaluation method to compare the level of cortical perfusion to the maximum number of counts within the cerebellum (max C), considered the area of reference. This study showed that SPECT imaging revealed abnormalities in several regions of the brain in both epilepsy groups. The refractory epilepsy dogs showed more frequency area of hypoperfusion in temporal lobe than non-refractory group with not statistically significance (P=0.28). The result suggests the lesion in temporal might be relevance with refractory epilepsy in canine patients.

Patterns of antiepileptic drug use in patients with potential refractory epilepsy in Texas Medicaid

ObjectivesAntiepileptic drug (AED) monotherapy is usually effective in 60% of the patients with epilepsy while the remaining patients have refractory epilepsy. This study compared treatment patterns (adherence, persistence, addition, and switching) associated with refractory and nonrefractory epilepsy. MethodsTexas Medicaid claims from 09/01/07–12/31/13 were analyzed, and patients eligible for the study 1) were between 18 and 62 years of age, 2) had a prescription claim for an AED during the identification period (03/01/08–12/31/11) with no prior baseline AED use (6-month), and 3) had evidence of epilepsy diagnosis within 6 months of AED use. Based on AED use in the identification period, patients were categorized into “refractory” (≥3AEDs) and “nonrefractory” (<3AEDs) cohorts. The index date was the date of the first AED claim. Patients in both cohorts were matched 1:1 using propensity scoring and compared for adherence (proportion of days covered (PDC) ≥80% vs. <80%), persistence, addition (yes/no), and switching (yes/no) using multivariate conditional regression models. Conditional logistic regression and Cox proportional hazard models were used to address the study objectives. ResultsOf the 10,599 eligible patients, 2798 (26.5%) patients in the refractory cohort were matched to patients in the nonrefractory cohort. Patients in the refractory cohort had significantly higher (p < 0.005) mean (±Standard deviation (SD)) adherence (88.6% (±19.1%) vs. 77.0% ± (25.8%)) and persistence (328.0 (±87.3) days vs. 294.9 ± (113.4) days) as compared with patients in the nonrefractory cohort. Compared with patients with nonrefractory epilepsy, patients with refractory epilepsy were 3.6 times (odds ratio (OR) = 3.553; 95% confidence interval (CI) = 3.060–4.125; p < 0.0001) more likely to adhere to AEDs and had a 34.7% (hazard ratio (HR) = 0.653; 95% CI = 0.608–0.702; p < 0.0001) lower hazard rate of discontinuation of AEDs. Also, patients with refractory epilepsy were 3.7 times (OR = 3.723; 95% CI = 2.902–4.776; p < 0.0001) more likely to add an alternative AED and 3.6 times (OR = 3.591; 95% CI = 3.010–4.284; p < 0.0001) more likely to switch to an alternative AED. ConclusionPatients with refractory epilepsy were significantly more likely to adhere and persist to AED regimen and were significantly more likely to add and switch to an alternative AED than patients with nonrefractory epilepsy.

Alteraciones del sueño y calidad de vida en la epilepsia parcial refractaria: resultados del estudio SLEEP

Sleep disorders are frequent among patients with epilepsy and are correlated with a poorer quality of life. To evaluate the prevalence of sleep disorders in patients with refractory and non-refractory focal epilepsy, and to explore the influence of these alterations on the quality of life of these patients. An epidemiological, controlled, cross-sectional study was conducted in 150 outpatient neurology services. Patients who had been treated with two antiepileptic drugs since the onset of the disease (18-55 years) were recruited for the study. The sample included 237 patients with non-refractory focal epilepsy and 264 patients with refractory focal epilepsy. Twenty-two per cent of the non-refractory epilepsy group and 45% of the group with refractory epilepsy (p < 0.0001) suffered from some sleep disorder. The patients with refractory epilepsy had a poorer quality of life (p < 0.001) as measured with the quality of life questionnaire QOLIE-10. A positive significant correlation was observed between quality of life and quality of sleep, in both chronic insomnia (r = 0.65; p < 0.0001) and excessive daytime sleepiness (r = 0.43; p < 0.0001). Sleep disorders are more frequent in refractory than in non-refractory epilepsy, and affect the patients' quality of life.

Obesity in adults with epilepsy

Sixty-eight percent of the US adult population is overweight, and 35% is obese. The rate of obesity in patients with epilepsy is unknown. Its determination was the goal of the present study. Weight and height were measured, and body mass index (BMI) was calculated in all newly evaluated patients with epilepsy at a single epilepsy center between 2003 and 2009. Five hundred fifty-four patients aged ≥16–87years were included (62.7% were women, 12.6% with primary generalized epilepsy, and 86.4% with localization-related epilepsy). Three hundred six (55.2%) patients were overweight or obese (BMI>25kg/m2) (95% confidence interval [CI]: 51.1%–59.3%), 173 (31.2%) were obese (BMI>30kg/m2) (95% CI: 27.5%–35.2%), and 24 (4.3%) were morbidly obese (BMI>40kg/m2). Overweight/obesity combined was more common in men (65.4% [95% CI: 58.8%–71.5%]) than in women (49% women [95% CI: 43.3%–54.3%]) (p≤0.001). The rate of overweight/obesity combined trended to be greater in blacks (67.9%) than in whites (51.9%). Obesity alone was more common in blacks (46.4%) than in whites (29.4%), with too few Hispanics and Asians to allow a comparison. Overweight/obesity and obesity rates were higher in patients with refractory than nonrefractory epilepsy (60.4% vs. 49.2% overweight, 36.9% vs.24.6% obesity). Obesity was more common in patients treated with polytherapy than those treated with monotherapy (37.7% vs. 25%). There were no associations between obesity and other disease characteristics such as epilepsy type, duration, or etiology. Obesity is common in patients with epilepsy, similar to the general population.

Hemimegalencephaly in an adult with normal intellectual function and mild epilepsy

Hemimegalencephaly is a rare congenital brain malformation, usually associated with mental retardation, * refractory epilepsy, and progressive neurological deficits. We report the case of a 19-year-old female with de novo diagnosis of right hemimegalencephaly, normal intellectual function, and history of non-refractory epilepsy. She presented with weakness and paraesthesia of the left leg. Extensive evaluation was negative for other causes for the weakness, which was attributed to progressive neurological damage secondary to long-standing subclinical epileptic activity in the hemimegalencephalic hemisphere. This patient underwent a cerebral fluorodeoxyglucose positron emission tomography that demonstrated near-normal cortical metabolism. Formal neuropsychological evaluation revealed mild deficits in the affected hemisphere, but preserved general intellectual function. This case illustrates the wide phenotypic variations in this condition and raises questions about prenatal counselling for hemimegalencephaly.

Intraoperative MRI with integrated functional neuronavigation-guided resection of supratentorial cavernous malformations in eloquent brain areas

Between March 2009 and January 2010, 36 patients with 38 supratentorial cavernous malformations in eloquent brain areas underwent surgery with the aid of intraoperative MRI (iMRI), functional neuronavigation, and electrocorticography (ECoG). To optimize outcomes, the hemosiderin-stained tissue surrounding the lesion in addition to the cavernous malformation itself (lesion) was microsurgically removed, leaving behind only small areas adjacent to, or overlapping with, functional areas. According to the Zabramski classification, there were 13 type I lesions, which all underwent total resection. There were 25 type II or III lesions with a surrounding hypointense rim, and all of these lesions were completely removed; the surrounding hypointense rims were completely removed in 15 patients and partially removed in 10. No new neurologic disorders occurred postoperatively. Twenty patients had preoperative epileptic seizures, nine of whom were refractory to treatment. During follow-up, seizure outcome was assessed using the Engel classification, and 11 patients with non-refractory epilepsy had a class I outcome. Of the nine patients with refractory epilepsy, seven (77.8%) had a class I outcome, one (11.1%) had a class II outcome, and one (11.1%) had a class III outcome.

Altered Expression of Synaptotagmin I In Temporal Lobe Tissue of Patients With Refractory Epilepsy

Synaptotagmin I is a key synaptic protein involved in both exocytosis and endocytosis. We aimed to investigate Synaptotagmin I expression in the anterior temporal neocortex of epilepsy patients, and to explore the possible role of Synaptotagmin I in refractory epilepsy. In the present study, 30 epilepsy patients were divided into refractory epilepsy and non-refractory epilepsy groups, another 15 histologically normal anterior temporal lobes from head trauma patients were used as control group. The results were compared among different groups. The findings were consistently observed using immunohistochemistry, immunofluorescence, and Western blotting technique. Synaptotagmin I was mainly expressed in the cytoplasm and cytomembrane of neurons. The expression of Synaptotagmin I in refractory epilepsy group was significantly higher than that in the control and non-refractory epilepsy groups. These findings provide new information in the epileptogenesis of refractory epilepsy, and suggest that Synaptotagmin I might be involved in human refractory epilepsy. Further studies will be required to elucidate the mechanism by which Synaptotagmin I plays role in refractory epilepsy.

Chronic Sorrow and Coping in Families of Children with Epilepsy

Epilepsy, a common problem in child neurology, affects the entire family. There is a potential for such psychosocial consequences as parental chronic sorrow and alterations in coping. In this study, 67 parents completed brief questionnaires about their sorrow and coping styles. Results demonstrated chronic sorrow as measured by the Adapted Burke Questionnaire (10.45 +/- 7.9). Interestingly, the total score was not significantly different between parents of children with refractory and nonrefractory epilepsy or parents of children with comorbid or without comorbid conditions. Selection of the individual item disbelief, however, was significantly increased in parents of children with nonrefractory epilepsy, and selection of the item anger was significantly increased in parents of children with comorbid conditions. Parental coping styles were similar to those reported in the normative data for the instrument used, the Coping Health Inventory for Parents (CHIP). The correlation between chronic sorrow and coping was significant between the grief component of sorrow and Coping Pattern II of the CHIP. Implications for practice include earlier identification of parental feelings of sorrow and coping styles, which may contribute to a positive outcome.

The Prognostic Value of [18F]FDG‐PET in Nonrefractory Partial Epilepsy

Regional abnormalities of cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG-PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG-PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease. We investigated interictal abnormalities of cerebral glucose metabolism by using FDG-PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after > or =2 years of follow-up. Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty-one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow-up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow-up period of 43 months. Regional hypometabolism in FDG-PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.

How long do new‐onset seizures in children last?

Although there are data on the duration of seizures in patients with refractory epilepsy, little is known about the duration of seizures in nonrefractory epilepsy populations. In a prospective study, seizure duration was determined in 407 children with a first unprovoked seizure using a structured interview and review of medical and ambulance records. Analysis focused on the distribution of seizure duration and on the conditional probability that a seizure would stop once it had already lasted for a specified time. Seizures lasted > or = 5 minutes in 50% of cases, > or = 10 minutes in 29%, > or = 20 minutes in 16%, and > or = 30 minutes in 12%. Seizure duration data were best fit as the sum of two exponential distributions, one with a mean of 3.6 minutes accounting for 76% of cases and the other with a mean of 31 minutes accounting for 24% of cases. The longer a seizure lasted, the less likely it was to stop within the next few minutes. In the 182 children with 2 or more seizures, the durations of the first and second seizures were highly correlated (r = 0.395, p < 0.0001). We conclude that the distribution of seizure duration in children with a first unprovoked seizure differs markedly from that observed in patients with refractory epilepsy. A subgroup of patients are predisposed to prolonged seizures. The data suggest that, once a seizure lasts for more than 5-10 minutes, it is unlikely to stop spontaneously within the next few minutes, and intervention is therefore indicated. These findings also support the continued use of the current definition of status epilepticus as a seizure lasting for 30 minutes or longer for epidemiologic studies.