Although the general utility of voxel-based processing of structural magnetic resonance imaging (MRI) data for detecting occult lesions in focal epilepsy is established, many differences exist among studies, and it is unclear which processing method is preferable. The aim of this study was to compare the ability of commonly used methods to detect epileptogenic lesions in magnetic resonance MRI-positive and MRI-negative patients, and to estimate their diagnostic yield.Methods
We identified 144 presurgical focal epilepsy patients, 15 of whom had a histopathologically proven and MRI-visible focal cortical dysplasia; 129 patients were MRI negative with a clinical hypothesis of seizure origin, 27 of whom had resections. We applied four types of voxel-based morphometry (VBM), three based on T1 images (gray matter volume, gray matter concentration, junction map [JM]) and one based on normalized fluid-attenuated inversion recovery (nFSI). Specificity was derived from analysis of 50 healthy controls.Results
The four maps had different sensitivity and specificity profiles. All maps showed detection rates for focal cortical dysplasia patients (MRI positive and negative) of >30% at a strict threshold of p < 0.05 (family-wise error) and >60% with a liberal threshold of p < 0.0001 (uncorrected), except for gray matter volume (14% and 27% detection rate). All maps except nFSI showed poor specificity, with high rates of false-positive findings in controls. In the MRI-negative patients, absolute detection rates were lower. A concordant nFSI finding had a significant positive odds ratio of 7.33 for a favorable postsurgical outcome in the MRI-negative group. Spatial colocalization of JM and nFSI was rare, yet showed good specificity throughout the thresholds.Significance
All VBM variants had specific diagnostic properties that need to be considered for an adequate interpretation of the results. Overall, structural postprocessing can be a useful tool in presurgical diagnostics, but the low specificity of some maps has to be taken into consideration.
The current opinion in epilepsy surgery is that successful surgery is about removing pathological cortex in the anatomic sense. This contrasts with recent developments in epilepsy research, where epilepsy is seen as a network disease. Computational models offer a framework to investigate the influence of networks, as well as local tissue properties, and to explore alternative resection strategies. Here we study, using such a model, the influence of connections on seizures and how this might change our traditional views of epilepsy surgery. We use a simple network model consisting of four interconnected neuronal populations. One of these populations can be made hyperexcitable, modeling a pathological region of cortex. Using model simulations, the effect of surgery on the seizure rate is studied. We find that removal of the hyperexcitable population is, in most cases, not the best approach to reduce the seizure rate. Removal of normal populations located at a crucial spot in the network, the “driver,” is typically more effective in reducing seizure rate. This work strengthens the idea that network structure and connections may be more important than localizing the pathological node. This can explain why lesionectomy may not always be sufficient.
Rate, reasons, and predictors of antiepileptic drug (AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation.Methods
The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions. The probabilities of withdrawing for terminal remission, and of achieving sustained remission while still on treatment, were also evaluated. The roles of sex, age at diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with hazard ratios and 95% confidence intervals.Results
Seven hundred thirty-one of 747 individuals were treated with one or more AEDs during the disease course. The three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported reasons for AED withdrawal were, in decreasing order, terminal remission, ineffectiveness, and adverse events. The probability of withdrawing the first AED for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years. Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for adverse events. Reasons for withdrawal varied with individuals’ age, sex, disease characteristics, and drugs.Significance
The initial AED given was retained in the majority of cases. Terminal remission, lack of efficacy, and adverse effects were, in decreasing order, the commonest reasons for AED discontinuation. Withdrawal could be predicted by age at diagnosis, sex, and clinical characteristics and varies among drugs.
Seizure outcome after hippocampal deep brain stimulation in patients with refractory temporal lobe epilepsy: A prospective, controlled, randomized, double-blind study
We designed a prospective, randomized, controlled, double-blind study to evaluate the efficacy of hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporary lobe epilepsy (TLE).Methods
Sixteen adult patients with refractory TLE were studied. Patient's workup included medical history, interictal and ictal electroencephalography (EEG), and high-resolution 1.5T magnetic resonance imaging (MRI). Patients were randomized on a 1:1 proportion to an active (stimulation on) or to a control (no stimulation) arm. After implantation, patients were allowed to recover for 1 month, which was followed by a 1-month titration (or sham) period. The 6-month blinded phase started immediately afterward. A postoperative MRI confirmed the electrode's position in all patients. All patients received bipolar continuous stimulation. Stimulus duration was 300 μs and frequency was 130 Hz; final intensity was 2 V. Patients were considered responders when they had at least 50% seizure frequency reduction.Results
All patients had focal impaired awareness seizures (FIAS, complex partial seizures), and 87% had focal aware seizures (FAS, simple partial seizures). Mean preoperative seizure frequency was 12.5 ± 9.4 (mean ± standard deviation) per month. MRI findings were normal in two patients, disclosed bilateral mesial temporal sclerosis (MTS) in three, left MTS in five, and right MTS in six patients. An insertional effect could be noted in both control and active patients. In the active group (n = 8), four patients became seizure-free; seven of eight were considered responders and one was a nonresponder. There was a significant difference regarding FIAS frequency between the two groups from the first month of full stimulation (p < 0.001) until the end of the blinded phase (p < 0.001). This was also true for FAS, except for the third month of the blinded phase.Significance
Hip-DBS was effective in significantly reducing seizure frequency in patients with refractory TLE in the active group, as compared to the control group. Fifty-percent of the patients in the active group became seizure-free. The present study is the larger prospective, controlled, double-blind study to evaluate the effects of Hip-DBS published to date.
Health care resource utilization before and after perampanel initiation among patients with epilepsy in the United States
The purpose of this study was to evaluate changes in health care resource utilization following the initiation of perampanel for the treatment of epilepsy in the United States.Methods
Health care claims from Symphony Health's Integrated Dataverse database between December 2012 and November 2015 were analyzed. Patients newly initiated on perampanel, having ≥1 epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 345.xx, ICD-10-CM code G40.xxx) or nonfebrile convulsion (ICD-9-CM code 780.39, ICD-10-CM code R56.9) diagnosis, and having ≥6 months of baseline and observation periods were included. Patients <12 years old at perampanel initiation were excluded.Results
Of the 2,508 perampanel patients included in the study, the mean [median] (±standard deviation [SD]) age was 35.8  (±16.0) years and 56.2% were female. The mean [median] (±SD) observation duration was 459.8  (±146.3) days in the postperampanel period. The postperampanel period was associated with significantly lower rates of all health care resource utilization outcomes than the pre-period. For the post- versus pre-period, perampanel users had 42.3 versus 53.8 overall hospitalizations per 100 person-years (rate ratio [RR] = 0.80, p < 0.001) and 1,240.2 versus 1,343.8 outpatient visits per 100 person-years (RR = 0.91, p < 0.001). Epilepsy-related hospitalizations and outpatient visits were 25.2 versus 33.6 per 100 person-years (RR = 0.76, p < 0.001) and 327.0 versus 389.0 per 100 person-years (RR = 0.84, p < 0.001), respectively. Additionally, a significantly lower rate of status epilepticus in the post-period (1.8 events per 100 person-years) was observed compared to the pre-period (4.4 events per 100 person-years; RR = 0.43, p < 0.001). The monthly time trend of hospitalizations showed an increasing trend leading up to the initiation of perampanel, after which the hospitalizations decreased steadily.Significance
Use of perampanel for the treatment of epilepsy was associated with significant reduction in all-cause and epilepsy-related health care resource utilization, including hospitalizations, especially for status epilepticus, and outpatient visits.
Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug-refractory epilepsy
ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy.Methods
Status epilepticus was induced using either intra-amygdala kainic acid or pilocarpine to characterize the acute- and long-term changes in hippocampal P2Y expression. P2Y expression was also investigated in brain tissue from patients with temporal lobe epilepsy. Finally, we analyzed the effects of two specific P2Y agonists, ADP and UTP, on seizure severity and seizure-induced cell death.Results
Both intra-amygdala kainic acid and pilocarpine-induced status epilepticus increased the transcription of the uracil-sensitive P2Y receptors P2ry2, P2ry4, and P2ry6 and decreased the transcription of the adenine-sensitive P2Y receptors P2ry1, P2ry12, P2ry13. Protein levels of P2Y1, P2Y2, P2Y4, and P2Y6 were increased after status epilepticus, whereas P2Y12 expression was decreased. In the chronic phase, P2ry1, P2ry2, and P2ry6 transcription and P2Y1, P2Y2, and P2Y12 protein levels were increased with no changes for the other P2Y receptors. In hippocampal samples from patients with temporal lobe epilepsy, P2Y1 and P2Y2 protein expression was increased, whereas P2Y13 levels were lower. Demonstrating a functional contribution of P2Y receptors to seizures, central injection of ADP exacerbated seizure severity, whereas treatment with UTP decreased seizure severity during status epilepticus in mice.Significance
The present study is the first to establish the specific hippocampal expression profile and function of the P2Y receptor family after experimental status epilepticus and in human temporal lobe epilepsy and offers potential new targets for seizure control and disease modification.
A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults
The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults.Methods
Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65–80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65–80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale).Results
Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5).Significance
LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance.
What would it mean if epilepsy could be diagnosed much earlier? More rapid treatment and fewer tests for sure, but it could also help reduce the incredible angst, frustration and general disruption that people often face whilst waiting for a diagnosis.
Researchers at University of Illinois at Chicago (UIC) have discovered that complex cellular process in epileptic brain tissue leave tell-tale signs that distinguish it from non-epileptic tissue. This can be detected using a non-invasive technique called magnetic resonance spectroscopy (MRS). Current non-invasive investigations can’t detect epileptic tissue of less than 10 square centimetres, meaning that it is often missed and people who need treatment do not receive it. Some people are referred for more invasive tests that can be painful and carry increased risks.
The MRS method used here was able to identify epileptic regions that were a lot smaller, which means that it could potentially help diagnose epilepsy a lot more efficiently.
During the study, the team used a powerful MRS scanner (based at Wayne State University, Detroit) to analyse epileptic, ‘less-epileptic’ and non-epileptic brain tissue removed from nine people as part of epilepsy surgery. More specifically, they wanted to look at the levels of chemicals linked to metabolic processes in the tissues’ cells (known as their metabolomic signature).
They found that tissue with a lot of epileptic activity had higher levels of compounds called creatine, phosphocreatine and choline, but lower levels of lactate, which is a strong indicator of abnormal metabolism. The researchers then examined the tissue more closely in the laboratory and saw that epileptic tissue had many more blood vessels than ‘less epileptic’ and non-epileptic tissue. Genetic analysis also showed that epileptic tissue had greater activation of genes linked to blood supply formation and changes in metabolism.
The reason for the altered metabolomic signature in the epileptic tissue is not entirely clear, but Senior Author Dr Jeffrey Loeb says: “These are areas of the brain where large populations of neurons are firing often, and this uses up a lot of energy, so it’s not surprising that we see an altered metabolic profile with a massive expansion of blood vessels.”
What happens next?
Further studies involving UIC and Wayne State are already underway to fully translate these findings to the clinical setting, where people would undergo a non-invasive scan (very similar to an MRI) and the metabolomic signature of their brain tissue would be revealed. If successful, this could revolutionise the diagnosis, and the treatment, of epilepsy. It could even lead to therapies that prevent epilepsy from developing after a brain injury.
Dr Loeb comments: “The technology will allow us to diagnose epilepsy much earlier. This is critical if we are to develop new treatments to prevent epilepsy from developing after a head injury, stroke, or brain tumor.”
This study is published in the scientific journal, Epilepsia.
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A version of levetiracetam called Levetiracetam-Lupin, made by Lupin (Europe) Ltd, has been discontinued in the UK. This means that this form of levetiracetam is no longer available in the UK, and if you currently take it you will be changed to a different version. If you are at all worried about this, please contact your doctor, epilepsy nurse or pharmacist as soon as possible.
Dr Ted Reynolds is one of the founders of the Fund for Epilepsy and a Past President of the International League Against Epilepsy. Now retired, Ted continues with his interest in the history of epilepsy in medicine. We went down to talk to him about the earliest descriptions of epilepsy by the Babylonians over 5,000 years ago.
Decreased levels of active uPA and KLK8 assessed by [111In]MICA-401 binding correlate with the seizure burden in an animal model of temporal lobe epilepsy
Urokinase-type plasminogen activator (uPA) and kallikrein-related peptidase 8 (KLK8) are serine proteases that contribute to extracellular matrix (ECM) remodeling after brain injury. They can be labelled with the novel radiotracer [111In]MICA-401. As the first step in exploring the applicability of [111In]MICA-401 in tracing the mechanisms of postinjury ECM reorganization in vivo, we performed in vitro and ex vivo studies, assessing [111In]MICA-401 distribution in the brain in two animal models: kainic acid–induced status epilepticus (KASE) and controlled cortical impact (CCI)–induced traumatic brain injury (TBI).Methods
In the KASE model, in vitro autoradiography with [111In]MICA-401 was performed at 7 days and 12 weeks post-SE. To assess seizure burden, rats were monitored using video-electroencephalography (EEG) for 1 month before the 12-week time point. In the CCI model, in vitro autoradiography was performed at 4 days and ex vivo autoradiography at 7 days post-TBI.Results
At 7 days post-SE, in vitro autoradiography revealed significantly decreased [111In]MICA-401 binding in hippocampal CA3 subfield and extrahippocampal temporal lobe (ETL). In the chronic phase, when animals had developed spontaneous seizures, specific binding was decreased in CA3 and CA1/CA2 subfields of hippocampus, dentate gyrus, ETL, and parietal cortex. Of interest, KASE rats with the highest frequency of seizures had the lowest hippocampal [111In]MICA-401 binding (r = −0.76, p ≤ 0.05). Similarly, at 4 days post-TBI, in vitro [111In]MICA-401 binding was significantly decreased in medial and lateral perilesional cortex and ipsilateral dentate gyrus. Ex vivo autoradiography at 7 days post-TBI, however, revealed increased tracer uptake in perilesional cortex and hippocampus, which was likely related to tracer leakage due to blood–brain barrier (BBB) disruption.Significance
Strong association of reduced [111In]MICA-401 binding with seizure burden in the KASE model suggests that analysis of reduced levels of active uPA/KLK8 represents a novel biomarker candidate to be explored as a biomarker for epilepsy severity. However, limited BBB permeability of [111In]MICA-401 currently limits its application in vivo.
This study aimed to identify noninvasive biomarkers of human epilepsy that can reliably detect and localize epileptic brain regions. Having noninvasive biomarkers would greatly enhance patient diagnosis, patient monitoring, and novel therapy development. At the present time, only surgically invasive, direct brain recordings are capable of detecting these regions with precision, which severely limits the pace and scope of both clinical management and research progress in epilepsy.Methods
We compared high versus low or nonspiking regions in nine medically intractable epilepsy surgery patients by performing integrated metabolomic–genomic–histological analyses of electrically mapped human cortical regions using high-resolution magic angle spinning proton magnetic resonance spectroscopy, cDNA microarrays, and histological analysis.Results
We found a highly consistent and predictive metabolite logistic regression model with reduced lactate and increased creatine plus phosphocreatine and choline, suggestive of a chronically altered metabolic state in epileptic brain regions. Linking gene expression, cellular, and histological differences to these key metabolites using a hierarchical clustering approach predicted altered metabolic vascular coupling in the affected regions. Consistently, these predictions were validated histologically, showing both neovascularization and newly discovered, millimeter-sized microlesions.Significance
Using a systems biology approach on electrically mapped human cortex provides new evidence for spatially segregated, metabolic derangements in both neurovascular and synaptic architecture in human epileptic brain regions that could be a noninvasively detectable biomarker of epilepsy. These findings both highlight the immense power of a systems biology approach and identify a potentially important role that magnetic resonance spectroscopy can play in the research and clinical management of epilepsy.
Nocturnal seizures are associated with more severe hypoxemia and increased risk of postictal generalized EEG suppression
Patients with epilepsy have 20-fold risk of sudden death when compared to the general population. Uncontrolled seizures is the most consistent risk factor, and death often occurs at night or in relation to sleep. We examined seizure-related respiratory disturbances in sleep versus wakefulness, focusing on periictal oxygen saturation. Respiratory measures were examined in 48 recorded seizures (sleep, n = 23, wake, n = 25) from 20 adult patients with epilepsy. Seizures from sleep were associated with lower saturation, as compared to seizures from wakefulness, both during ictal (sleep median = 90.8, wake median = 95.5; p < 0.01) and postictal periods (sleep median = 94.3, wake median = 96.9; p = 0.05). Compared to wake-related seizures, seizures from sleep were also associated with a larger desaturation drop (sleep median = −4.2, wake median = −1.2; p = 0.01). Postictal generalized electroencephalography (EEG) suppression (PGES) occurred more frequently after seizures from sleep (39%), as compared to wake-related seizures (8%, p = 0.01). Our findings suggest that nocturnal seizures may entail a higher sudden unexpected death in epilepsy (SUDEP) severity burden, as they are associated with more severe and longer hypoxemia events, and more frequently followed by PGES, both factors implicated in sudden death.
The biologic processes underlying epileptogenesis following a brain insult are not fully understood, but several lines of evidence suggest that hyperphosphorylation of tau may be an important factor in these processes. To provide further insight into the causal relationship between tau and epileptogenesis, this study applied amygdala kindling to rTg4510 mice that, concurrent with other pathologies, overexpress phosphorylated tau, tau knockout mice, or their respective wild-type controls. Mice were electrically stimulated twice daily, 5 days per week for 3 weeks. Electroencephalography was recorded to measure the primary afterdischarge duration, and the behavioral progression of kindling-induced seizures was assessed. rTg4510 mice (n = 10) had increased primary afterdischarge durations (p < 0.001), and significantly more rapid progression of kindling (p < 0.001), compared with wild-type mice (n = 10). Tau knockout mice (n = 7), however, did not differ from their wild-type counterparts (n = 8) on any of the seizure outcomes. These results suggest that Tg4510 mice are more vulnerable to epileptogenesis, but that the presence of tau itself is not necessary for kindling epileptogenesis to occur.
Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery
To determine the predictors of cognitive function in patients with drug-resistant gelastic seizures (GS) related to hypothalamic hamartoma (HH) before and after stereotactic radiofrequency thermocoagulation surgery (SRT).Methods
We studied 88 patients with HH who underwent SRT between October 1997 and December 2014. Patients received neuropsychological tests preoperatively and postoperatively. Based on the preoperative measures, patients were categorized as “high-functioning” (full-scale intelligence quotient [FSIQ] ≥70; n = 48) and “low-functioning” group (FSIQ <70; n = 40). Univariate and multivariate linear regression analyses determined the clinical, electroencephalography (EEG), and imaging factors associated with preoperative cognitive function as well as postoperative cognitive change.Results
Eighty-seven patients (98.8%) were followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them achieved GS remission at the last hospital visit. Neuropsychological performance was significantly improved after surgery in both groups. Multivariate linear regression analysis showed that a smaller HH size (p = 0.002) and a smaller number of antiepileptic drugs (p < 0.001) were preoperatively associated with better neuropsychological performance. Multivariate linear regression analysis showed that better postoperative improvement in cognition was associated with a shorter duration of epilepsy (p = 0.03).Significance
Cognitive impairment related to epileptic encephalopathy may improve following SRT in substantial proportions of HH patients. Reduced improvement in postoperative cognitive function in patients with longer duration of epilepsy warrants further studies to determine if earlier SRT provides a greater chance of postoperative cognitive improvement in patients with HH.
Hippocampal sclerosis (HS), the most common cause of refractory temporal lobe epilepsy, is associated with hippocampal volume loss and increased T2 signal. These can be identified on quantitative imaging with hippocampal volumetry and T2 relaxometry. Although hippocampal segmentation for volumetry has been automated, T2 relaxometry currently involves subjective and time-consuming manual delineation of regions of interest. In this work, we develop and validate an automated technique for hippocampal T2 relaxometry.Methods
Fifty patients with unilateral or bilateral HS and 50 healthy controls underwent T1-weighted and dual-echo fast recovery fast spin echo scans. Hippocampi were automatically segmented using a multi-atlas–based segmentation algorithm (STEPS) and a template database. Voxelwise T2 maps were determined using a monoexponential fit. The hippocampal segmentations were registered to the T2 maps and eroded to reduce partial volume effect. Voxels with T2 >170 msec excluded to minimize cerebrospinal fluid (CSF) contamination. Manual determination of T2 values was performed twice in each subject. Twenty controls underwent repeat scans to assess interscan reproducibility.Results
Hippocampal T2 values were reliably determined using the automated method. There was a significant ipsilateral increase in T2 values in HS (p < 0.001), and a smaller but significant contralateral increase. The combination of hippocampal volumes and T2 values separated the groups well. There was a strong correlation between automated and manual methods for hippocampal T2 measurement (0.917 left, 0.896 right, both p < 0.001). Interscan reproducibility was superior for automated compared to manual measurements.Significance
Automated hippocampal segmentation can be reliably extended to the determination of hippocampal T2 values, and a combination of hippocampal volumes and T2 values can separate subjects with HS from healthy controls. There is good agreement with manual measurements, and the technique is more reproducible on repeat scans than manual measurement. This protocol can be readily introduced into a clinical workflow for the assessment of patients with focal epilepsy.
Differentiation between psychogenic nonepileptic seizures (PNES) and generalized convulsive epileptic seizures (ES) is important for appropriate triaging in the emergency department (ED). This can be difficult in the ED, as the event is often not witnessed by a medical professional. In the current study, we investigated whether anion gap (AG), bicarbonate, and the Denver Seizure Score (DSS) could differentiate between PNES and ES. Of a total of 1,354 subjects reviewed from a tertiary care medical center, 27 PNES and 27 ES patients were identified based on clinical description and subsequent electroencephalogram. Multivariate logistic regression analysis and receiver operating characteristic curves were used to determine whether there was an association between seizure type and AG, bicarbonate, or DSS (24-bicarbonate + 2 × [AG-12]) when samples were drawn within 24 h of the concerning event. The result showed that sensitivity and negative predictive value dropped markedly for all measures if samples were drawn >2 h after the event; the sensitivity was similar for AG and DSS and higher than for bicarbonate. We propose that AG > 10 (sensitivity of 81.8%, specificity of 100%) in the first 2 h after the event could be used as a potential tool in the ED to help differentiate between PNES and ES.