Seizure-free Patients Research Articles

Long-term Outcome of Resective Epilepsy Surgery in Patients With Lennox-Gastaut Syndrome.

We aimed to evaluate the long-term outcome of resective epilepsy surgery in patients with Lennox-Gastaut syndrome (LGS). We reviewed the case reports of 90 patients with LGS who had undergone resective surgery between 2003 and 2014 at the Severance Children's Hospital and managed them for a minimum period of 2 years. At the time of surgery, the patients were between 3.0 and 23.5 years old (mean ± SD: 9.3 ± 4.4). The time from seizure onset to surgery ranged from 0.7 to 20.1 years (7.2 ± 4.3). On postoperative follow-up for an average period of 6.1 ± 2.2 years (range: 2.1-11.4 years), 45 patients (50.0%) had no seizures, and 15 (16.7%) reported infrequent seizures. Seizure-free outcomes were achieved in 15 of the 21 (71.4%) hemispherectomies, 23 of the 51 (45.1%) multilobar resections, and 7 of the 18 (38.9%) single lobar resections. On high-resolution MRIs, 20 patients (22.2%) had negative findings, 8 of whom (40.0%) became seizure-free after resective surgery. Malformation of cortical development was the most common pathologic finding and was noted in 57 patients (63.3%). Seizure-free patients achieved better adaptive behavior and social competence than did patients with persistent seizures at the second (2-3 years after surgery) and third (4-6 years after surgery) follow-ups, as indicated by social quotients (P < .05). Resective surgery is a viable option in some patients to treat seizures that are associated with LGS, with a high probability of seizure control and better adaptive function.

Cognitive outcomes more than 5 years after temporal lobe epilepsy surgery: Remarkable functional recovery when seizures are controlled

PurposeEpilepsy surgery can be a successful treatment option for temporal lobe epilepsy but there are concerns about accelerated memory decline in long-term follow-up. Method161 adult operated (77 right, 84 left temporal resections) versus a heterogeneous group of 208 non-operated patients with focal epilepsies were consecutively recruited and re-evaluated focusing on memory, executive functions, and vocational outcome after follow-up intervals of >5 years (5–22 years, mean 8 ± 3 years). ResultsMajor losses in the operated group manifest early, at one-year follow-up. Few patients declined further. Long-term changes after surgery did not differ from those observed without surgery. The factor “surgery” caused verbal memory decline, “seizure freedom” (operated 48%, non-operated 17%) was associated with recovery of verbal memory, and “drug reduction” positively affected the course of executive functions. In terms of the critical function of verbal memory, only 3–17% of seizure-free patients showed long-term decline whereas 16–20% showed improvement (operated and non-operated). Persistent seizures were associated with decline in 12–37% and improvement in 4–12% of patients. Improvement was related to longer retest intervals and was stronger in younger patients. Independent of surgery or seizure outcome, the vocational status remained unchanged or change was negative (22%) rather than positive (3%). ConclusionsPatients’ cognitive course 5–22 years after surgery is stable and may even be positive if epilepsy is controlled and drug load reduced. Depending on seizure outcome, recovery is more frequently observed than continuing decline. Recovery, however, takes time and age is a limiting factor.

Analysis of fractional anisotropy and mean diffusivity in refractory and non-refractory idiopathic generalized epilepsies

PurposeTo compare white matter bundles and fiber tract changes in seizure-free and non-seizure-free idiopathic generalized epilepsy (IGE) patients. MethodForty adult patients with IGE underwent a 3 T brain MRI with DTI sequences. According to seizure control status, eighteen patients were classified as refractory (R) if they had presented at least one incapacitating seizure in the previous six months, while on appropriate antiepileptic drug treatment. Twenty two seizure-free patients with adequate seizure control were considered non-refractory (NR). We compared fractional anisotropy (FA) and mean diffusivity (MD) values in sixteen white matter tracts in the R and NR groups, and in twenty healthy subjects. ResultsR and NR groups did not differ in gender, age and education. We found decreased FA in two tracts in the R group (forceps major and right uncinate fasciculus) and approaching statistical significance in two tracts in the NR group (right cingulate gyrus and right uncinate fasciculus) group, as well as increased MD in six tracts in the R group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi, and right cingulate gyrus) and in five tracts in the NR group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi), compared to controls. No differences were noted comparing FA and MD values between R and NR groups. ConclusionsIn our patient population, refractory IGE patients on adequate antiepileptic drug treatment did not present more severe white matter tract involvement compared to non-refractory patients.

Prognostic Factors and Longitudinal Change in Long-Term Outcome of Frontal Lobe Epilepsy Surgery

We aimed to investigate the possible predictive factors and longitudinal change in long-term surgical outcome after refractory frontal lobe epilepsy surgery. We retrospectively reviewed 82 patients who underwent frontal lobe resection. Invasive monitoring was performed in 43 patients. All patients were followed-up for a minimum of 3 years after surgery. Univariate and multivariate analyses were used to evaluate the predictors. The Kaplan-Meier survival curve showed the estimated probability of complete seizure freedom, and a favorable outcome was defined as Engel class I at the last follow-up. The estimated probability of complete seizure freedom was 57.3% at 1 year postoperatively, 51.2% at 2 years, and 50.0% at 5 years. Factors predictive of worse long-term outcome were lack of a lesion in the frontal lobe on magnetic resonance imaging, generalized/nonlocalized ictal discharge, use of subdural grids, and acute postoperative seizure (APOS). After the surgery, 44 patients (53.7%) had seizures at any time during the first 2 years. Five of 44 patients had seizure freedom at the last follow-up. After a seizure-free period of at least 6 months, seizure recurred in 6 patients by 6 months to 1 year (early recurrence) and in 9 patients by 1-3 years (late recurrence). Eight of 43 (18.6%) seizure-free patients had discontinued drugs. The overall seizure outcome after surgery changed most during the first 2 years. The presence of frontal focal lesions and ictal frontal rhythm predicted favorable outcome. However, APOS was predictive of early epilepsy recurrence.

Personalized prediction model for seizure-free epilepsy with levetiracetam therapy: a retrospective data analysis using support vector machine.

To predict the probability of a seizure-free (SF) state in patients with epilepsy (PWEs) after treatment with levetiracetam and to identify the clinical and electroencephalographic (EEG) factors that affect outcomes. Retrospective analysis of PWEs treated with levetiracetam for 3years identified 22 patients who were SF and 24 who were not. Before starting levetiracetam, 11 clinical factors and four EEG features (sample entropy of α, β, θ, δ) were identified. Overall, 80% of each the two groups were chosen to establish a support vector machine (SVM) model with 5-fold cross-validation, hold-out validation and jack-knife validation. The other 20% were used to predict the efficacy of levetiracetam. The mean impact value (MIV) algorithm was used to rank the relativity between factors and outcomes. Compared with SF patients, not SF patients displayed a specific decrease in EEG sample entropy in α band from the F4 channel, β band from Fp2 and F8 channels, θ band from C3 channel (P<0.05). The SVM model based on the clinical and EEG features yielded 72.2% accuracy of 5-fold cross-validation, 75.0% accuracy of jack-knife validation, 67.7% accuracy of hold-out validation in the training set and had a high prediction accuracy of 90% in test set (sensitivity was 100%, area under the receiver operating characteristic curve was 0.96). The feature of β band from Fp2 weighs heavily in the prediction model according to the mean impact value algorithm. The efficacy of levetiracetam on newly diagnosed PWEs could be predicted using an SVM model, which could guide antiepileptic drug selection.

Cepstrum Coefficient Analysis from Low-Frequency to High-Frequency Applied to Automatic Epileptic Seizure Detection with Bio-Electrical Signals

This study analyzes bioelectrical signals to achieve automatic epileptic seizure detection. Electroencephalographic (EEG) signals were recorded with electrodes on healthy, epileptic seizure-free, and epileptic seizure patients. The challenges in this field are generally regarded to be the impacts of non-stationarity and nonlinearity in EEG signals. To address these challenges, this study attempts to recognize different brain statuses. The idea originated from a novel hypothesis that considers EEG signals as convolution signals and regards itself as the generation mechanism of EEG signals, to some extent. Based on this hypothesis, the nonlinear problem can be viewed as a deconvolution procedure. As such, the method can be simplified into three parts: eliminating non-stationary is used to catch high-frequency to low-frequency signals, which is followed by a local mean decomposition (LMD) algorithm; these signals are deconvoluted to form ultra-high-dimensional feature sets, which is completely terminated by the mel-frequency cepstrum coefficients (MFCC) algorithm; and several classifiers are combined to achieve highly accurate recognition results and to verify the superiority and reasonableness of this method. The publicly available EEG database from the University of Bonn, Germany is employed to demonstrate the effectiveness and outstanding performance of this method. According to the results, the method has the ability to attain a higher average classification accuracy than other methods in all of the four following cases: healthy (datasets A and B) versus epileptic seizure (dataset E), epileptic seizure-free (datasets C and D) versus epileptic seizure (dataset E), healthy (datasets A and B) versus epileptic seizure-free (datasets C and D) versus epileptic seizure (dataset E), and healthy (dataset A) versus healthy (dataset B) versus epileptic seizure-free (dataset C) versus epileptic seizure-free (dataset D) versus epileptic seizure (dataset E).

Left ventricular myocardial deformation abnormalities in seizure-free children with epilepsy

PurposeAlthough there is a higher risk of structural cardiac disease in people with epilepsy, there is no detailed advanced analysis of cardiac functions in patients with epilepsy. This study aimed to determine early echocardiographic findings of Left Ventricular (LV) dysfunction using cardiac strain technique in seizure-free children with epilepsy. MethodThe study investigated 60 children with epilepsy who had no seizures in the preceding 6 months, without any known cardiovascular disease and treated with one antiepileptic drug and 60 healthy subjects who underwent clinical evaluation including electrocardiography (ECG), standard echocardiography, tissue Doppler imaging (TDI) and two-dimensional Speckle Tracking Echocardiography (2DSTE). ResultsDespite the normal M-mode values, global longitudinal strain of the epilepsy of the control group was as follows: −16.86 ± 3.71, -18.95 ± 3.75, respectively (p = 0.001); global strain rates were determined as follows: -0.99 ± 0.23, -1.14 ± 0.31, respectively (p = 0003). The patients also had increased A-wave velocity, and decreased E/A ratio (p < 0.01). TDI results showed diastolic dysfunction as mirrored by significantly increased isovolemic relaxation time (IVRT), Early mitral inflow (E)/ Early diastolic velocity (E’), and Tei index (p < 0.01). There was no significant difference in LV torsion, Peak LV twist, and ECG parameters between the patients and the controls. ConclusionsIn seizure-free patients, cardiac systolic and diastolic functions were impaired when compared to healthy children. There was no difference in the patient group to explain the decline in cardiac functions and there may be unknown different factors besides the known risk factors.

Localization of the Epileptogenic Zone Using Interictal MEG and Machine Learning in a Large Cohort of Drug-Resistant Epilepsy Patients.

Objective: Epilepsy surgery results in seizure freedom in the majority of drug-resistant patients. To improve surgery outcome we studied whether MEG metrics combined with machine learning can improve localization of the epileptogenic zone, thereby enhancing the chance of seizure freedom.Methods: Presurgical interictal MEG recordings of 94 patients (64 seizure-free >1y post-surgery) were analyzed to extract four metrics in source space: delta power, low-to-high-frequency power ratio, functional connectivity (phase lag index), and minimum spanning tree betweenness centrality. At the group level, we estimated the overlap of the resection area with the five highest values for each metric and determined whether this overlap differed between surgery outcomes. At the individual level, those metrics were used in machine learning classifiers (linear support vector machine (SVM) and random forest) to distinguish between resection and non-resection areas and between surgery outcome groups.Results: The highest values, for all metrics, overlapped with the resection area in more than half of the patients, but the overlap did not differ between surgery outcome groups. The classifiers distinguished the resection areas from non-resection areas with 59.94% accuracy (95% confidence interval: 59.67–60.22%) for SVM and 60.34% (59.98–60.71%) for random forest, but could not differentiate seizure-free from not seizure-free patients [43.77% accuracy (42.08–45.45%) for SVM and 49.03% (47.25–50.82%) for random forest].Significance: All four metrics localized the resection area but did not distinguish between surgery outcome groups, demonstrating that metrics derived from interictal MEG correspond to expert consensus based on several presurgical evaluation modalities, but do not yet localize the epileptogenic zone. Metrics should be improved such that they correspond to the resection area in seizure-free patients but not in patients with persistent seizures. It is important to test such localization strategies at an individual level, for example by using machine learning or individualized models, since surgery is individually tailored.

Predictors of unprovoked seizures in surgically treated pyogenic brain abscess: Does perioperative adjunctive use of steroids has any protective effect?

ObjectiveThough outcome of brain abscess has been improved due to stereotactic drainage and appropriate antibiotic treatment, late unprovoked seizure often occurs after the abscess is resolved. The purpose of this study is to reveal the factors related to the late unprovoked seizure and effect of steroid on the prevention of seizure. Patients and MethodsFrom January 2002 to August 2016, 119 patients with supratentorial brain abscesses were retrospectively analyzed. Initial volume of abscess, surgical methods, use of antiepileptic drugs (AEDs), and seizure free survival according to the use of steroid were compared between seizure free and late unprovoked seizure patients groups. Factors related to the late unprovoked seizure were evaluated by multivariate logistic regression model. ResultsAll patients underwent surgery, which were either by burrhole aspiration or craniotomy. 22/119 patients (18.5%) had late unprovoked seizure. Initial abscess volume was significantly larger in the group of late unprovoked seizure (28.31 ± 22.68 cm3 vs. 17.03 ± 14.53 cm3, p = 0.015). The mean time to the late unprovoked seizure was 487.7 ± 446 days (range, 11–1369 days). Steroid was used to relieve perilesional edema in 35 patients. Proportion of late onset seizure was not different between the group of steroid non-use group and steroid use (17.1% vs. 19%, p = 0.52) and mean seizure free periods of steroid non-use group and steroid use group were 40.75 ± 9.23 months and 48.85 ± 8.50 months, respectively (P = 0.89, by log rank test). Initial presentation of seizure at the diagnosis of brain abscess and initial volume larger than 20.89 cm3 were risk factors for late unprovoked seizure with odds ratio of 4.1 (95% C.I 1.44–11.69) and 3.08 (95% C.I 1.19–7.96), respectively. ConclusionLate unprovoked seizure in patients with brain abscess was affected by initial presentation of seizure and initial volume of the abscess whereas methods of surgical intervention and steroid use had no effect on the occurrence of late unprovoked seizure.

Evoked directional network characteristics of epileptogenic tissue derived from single pulse electrical stimulation.

We investigated effective networks constructed from single pulse electrical stimulation (SPES) in epilepsy patients who underwent intracranial electrocorticography. Using graph analysis, we compared network characteristics of tissue within and outside the epileptogenic area. In 21 patients with subdural electrode grids (1 cm interelectrode distance), we constructed a binary, directional network derived from SPES early responses (<100 ms). We calculated in‐degree, out‐degree, betweenness centrality, the percentage of bidirectional, receiving and activating connections, and the percentage of connections toward the (non‐)epileptogenic tissue for each node in the network. We analyzed whether these network measures were significantly different in seizure onset zone (SOZ)‐electrodes compared to non‐SOZ electrodes, in resected area (RA)‐electrodes compared to non‐RA electrodes, and in seizure free compared to not seizure‐free patients. Electrodes in the SOZ/RA showed significantly higher values for in‐degree and out‐degree, both at group level, and at patient level, and more so in seizure‐free patients. These differences were not observed for betweenness centrality. There were also more bidirectional and fewer receiving connections in the SOZ/RA in seizure‐free patients. It appears that the SOZ/RA is densely connected with itself, with only little input arriving from non‐SOZ/non‐RA electrodes. These results suggest that meso‐scale effective network measures are different in epileptogenic compared to normal brain tissue. Local connections within the SOZ/RA are increased and the SOZ/RA is relatively isolated from the surrounding cortex. This offers the prospect of enhanced prediction of epilepsy‐prone brain areas using SPES.

Discontinuation of carbamazepine due to concerns of long-term consequences of enzyme induction.

SummaryObjectiveTreatment with carbamazepine (CBZ), a potent enzyme inducer, is known to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it has been postulated that patients on CBZ should be switched to noninducing antiepileptic drugs (AEDs). However, little is known about the seizure outcome following a CBZ switch in seizure‐free patients. We aimed to address this issue using a controlled observational study design.MethodsFifty‐eight patients taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due to concerns of long‐term adverse‐effects; 34 discontinued its therapy and 24 continued with CBZ. Six‐month seizure freedom was the primary end point. Furthermore, serum samples (total cholesterol (TC), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides, sex hormone–binding globulin (SHBG), free testosterone, and 25‐hydroxyvitamin D levels from before and at least 3 months after discontinuation or continuation were obtained from all patients.ResultsSeizure‐free patients had a 5‐fold elevated odds of seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51–49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG as well as a significant increase in that of free testosterone were found in the discontinuation group compared with those who continued CBZ. Nonsignificant changes in triglycerides and vitamin D levels were detected.SignificanceDiscontinuation of CBZ in seizure‐free patients seems to carry a moderate, but legitimate, risk of relapse. Conversely, our results indicate that CBZ might have unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.

The occurrence of seizures after ischemic stroke does not influence long-term mortality; a 26-year follow-up study

ObjectiveEpileptic seizures are a common complication after stroke. The relation between occurrence of seizures after stroke and long-term mortality remains elusive. We aimed to assess whether seizures in an early or late phase after ischemic stroke are an independent determinant of long-term mortality.MethodsWe prospectively included and followed 444 ischemic stroke patients with a first-ever supratentorial brain infarct for at least 2 years after their stroke regarding the occurrence of seizures. The final follow-up for mortality is from April 2015 (follow-up duration 24.5–27.8 years, mean 26.0 years, SD 0.9 years). We compared patients with early-onset seizures with all seizure-free patients, whereas the patients with late-onset seizures were compared with the 1-week survivors without any seizures. We used Cox-regression analyses to correct for possible confounding factors.ResultsKaplan–Meier analysis showed significantly higher mortality for the patients with early-onset seizures (p = 0.002) but after correction for known risk factors for (long term) mortality early-onset seizures had no independent influence on long-term mortality (HR 1.09; 95% CI 0.64–1.85). In patients with late-onset seizures, no significant influence from late-onset seizures on long-term mortality was found (univariate p = 0.717; multivariate HR 0.81; 95% CI 0.54–1.20).ConclusionBoth early-onset and late-onset seizures do not influence long-term mortality after ischemic stroke.

Relapse after treatment withdrawal of antiepileptic drugs for Juvenile Absence Epilepsy and Juvenile Myoclonic Epilepsy

PurposeConventional teaching is that juvenile myoclonic epilepsy (JME) and juvenile absence epilepsy (JAE) require lifelong antiepileptic drug (AED) treatment. We therefore wanted to determine how many patients attending our epilepsy service with JAE or JME went into 2 year remission, and then relapsed, both off and on AEDs. MethodThis was a retrospective case-notes review. Patients with JAE and JME were systematically ascertained from clinic lists and databases at one teaching hospital. Data was extracted systematically. Simple descriptive statistics were used. ResultsJAE: 14/36 (39%) were seizure free on AEDs for at least 2 years. Of the 6 (43%) attempting AED withdrawal, all (100%) relapsed, compared with only 25% of those who did not withdraw AEDs. Only 2/5 who relapsed and restarted AEDs regained remission.JME: 32/145 (22%) were seizure free on AEDs for at least 2 years. Of the 10 (31%) attempting AED withdrawal, 8 (80%) relapsed, compared with only 36% of those who did not withdraw AEDs. Only 2/8 who relapsed and restarted AEDs regained remission. ConclusionRemission rates for JAE and JME was lower than expected. Higher proportions of seizure free patients underwent physician-supervised withdrawal than anticipated. Relapse rates off AEDs were similar for JAE and JME, and at least twice as high as for those remaining on AEDs, and a further remission was not invariable on restarting AEDs. Our experience, comparing relapse in those withdrawing to those staying on AEDs will help in discussions with patients keen to try AED withdrawal.

Efficacy of antiepileptic drugs in the adjunctive treatment of refractory partial-onset seizures: Meta-analysis of pivotal trials

ObjectiveIn the absence of randomized clinical trials (RCTs) assessing the relative efficacy of antiepileptic drugs (AEDs), meta-analyses are useful resources for informing treatment choices. This meta-analysis assesses the relative efficacy and tolerability of AEDs for adjunctive treatment of refractory partial onset seizures (POS). MethodsA systematic literature review was conducted to identify pivotal AED trials serving as the basis for US Food and Drug Administration (FDA) approval. Inclusion criteria: 1) double-blind, placebo-controlled, parallel-group design, with 8- to 14-week maintenance period; 2) enrolled patients ≥16years with refractory POS, including complex partial seizures; 3) study was conducted between 1993 and 2013; and; 4) patients received FDA-approved dosage. Outcomes analyzed: 1) 50% responder rate (≥50% reduction from baseline in seizure frequency); 2) seizure freedom (proportion of seizure-free patients); and 3) discontinuation due to adverse events (AEs). DerSimonian and Laird random-effects model was used to derive odds ratios (OR) and 95% confidence intervals (CI). ResultsA total of 29 publications for 11 AEDs (eslicarbazepine, ezogabine, gabapentin, lacosamide, levetiracetam, perampanel, pregabalin, tiagabine, topiramate, vigabatrin, and zonisamide) were included in the meta-analysis. Tiagabine 56mg/day (OR 8.82, 95% CI: 2.77–28.11), pregabalin 600mg/day (OR 8.08, 95% CI: 5.45–11.98), and vigabatrin 3000mg/day (OR 6.23, 95% CI: 1.46–26.20) had the highest OR versus placebo of 50% response. The odds of seizure freedom were ≥7 times greater than placebo for levetiracetam 3000mg/day (OR 11.00, 95% CI: 2.08–58.06), vigabatrin 3000mg/day (OR 7.41, 95% CI: 1.31–41.84), and ezogabine 1200mg/day (OR 7.09, 95% CI: 0.36–58.06). Patients were more likely to discontinue any AED (except low-dose pregabalin) than placebo. ConclusionIn this meta-analysis of >9000 patients, those treated with AEDs were more likely than placebo to achieve seizure response or freedom. Patients receiving pregabalin, tiagabine, and vigabatrin had the highest odds of ≥50% reduction in seizures, and patients receiving ezogabine, levetiracetam, and vigabatrin had the highest odds of seizure freedom.

Zonisamide serum concentrations during pregnancy

PurposeTo investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy. MethodsSix hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and obstetrical data were also collected. Results144 serum concentrations from 23 pregnancies in 15 individual women with epilepsy were included (six on monotherapy). The mean ZNS serum concentration fell to a minimum of 58.6 ± 15.1%, while the C/D-ratio fell to as low as 55.1 ± 15.3% of the non-pregnant-value. The lowest values were seen in gestational months six to nine, and the individual nadir varied considerably (range: 24–81% of the non-pregnant value). Four out of ten previously seizure-free patients experienced breakthrough seizures. Gestational age, weight at birth and head circumference of the newborns were within the reference ranges. ConclusionsZNS serum concentrations may fall by over 40% during pregnancy, with large interindividual variability. In some patients, this may lead to worsened seizure control. These findings are in line with reports on other AEDs and suggest that regular therapeutic drug monitoring and dose adjustments may be useful.

F180. The effectiveness of high-density EEG visual analysis and electrical source imaging in detecting the epileptogenic zone in focal epilepsy

Introduction For patients who are not seizure-free despite adequate therapy with antiepileptic drugs, surgery is an important option for seizure resolution or significant improvement. Electrical source localization (ESI) of the Interictal Epileptiform Discharges (IEDs) based on high density EEG (HD-ESI) is considered a good estimator of the epileptogenic zone and its resection is associated to post-operative seizure control. With the help of sophisticated algorithms results are displayed as 3D images; however, not all centers have access to manpower or programs to carry out these algorithms. In this study, we were interested to determine the yield of localizing the epileptogenic area by visual analysis of the 256 EEG channels, and to compare the results with the 3D solution. Methods We analysed HD-EEG long term recordings of 20 operated patients suffering from drug-resistant, unifocal epilepsy (11 temporal lobe epilepsy, 13 women, age mean 29.1 ± 2.62 years). We compared the performance of ESI and visual HD-EEG analysis in terms of correctness with respect to the resected structures. In the visual analysis condition, we identified the 5 contacts with largest spikes. Furthermore, the population was divided in 3 groups: seizure-free patients (Engel IA), almost seizure-free patients (Engel IB-IID), no seizure-free (all other Engel classes). In a second part of the analysis, we correlated the outcome of patients with results of HD-ESI of two different parts of IEDs (50% of the rising phase of the IED, peak of the IED). Results Both ESI and visual analysis provided correct results for the detection of the epileptogenic area in the majority of cases (ESI accuracy = 80% versus HD-EEG analysis accuracy = 65%). In one case (left fronto-parietal dysplasia), ESI indicates a wrong localization while visual-inspection localizes correctly the IZ. In 12/20 patients the same source was found at the 50% of the rising phase of the IED and at the peak (75% of the seizure-free patients; 50% of almost seizure-free patients; 25% of no seizure-free patients). Conclusion Visual HD-EEG analysis provided correct localization on sublobar level in 65% of the patients, which is superior to localization with 19–32 electrodes, but inferior to ESI. Visual identification of the 5 most active channels is an easy localization tool, if technical support or specific computer skills are not available. Findings of visual HD-EEG represent a very good surrogate marker of the epileptogenic region. If available, ESI should be obtained, possibly after a first visual analysis. Moreover, we noted that different sources at the 50% of the rising phase of the spike and at its peak could be a negative predictor of the outcome of the surgery.

EQ-5D-based utilities and healthcare utilization in Thai adults with chronic epilepsy

Quality of life and resource use are key parameters that justify economic values in treatments for epilepsy. Health profiles and service utilization were assessed in 224 adults with 15.7years of epilepsy in two super-tertiary care facilities in Thailand. The European Quality of Life, 5-Dimension (EQ-5D)-based utilities and subsequent outpatient (OP) visits and hospitalizations were determined with respect to seizure control outcomes that were assessed by neurologists. Mean utility and visual analogue scale (VAS) scores were respectively higher in 67 patients who are seizure-free (0.82 and 78.9) than in 157 patients who had uncontrolled or persistent seizures, which were divided into seizure reduction (0.79 and 75.5) and no improvement in seizure frequency (0.72 and 73.5). Controlling for patient characteristics, those who are seizure-free had significantly higher utility and VAS scores than those with no improvement by 0.10 (95% confidence interval (CI): 0.03–0.17) and 6.25 (95% CI: 0.09–12.41), respectively. Seizure-free patients were less likely to report pain or discomfort, as compared with patients with seizure reduction (odds ratio (OR): 0.41, 95% CI: 0.19–0.90) and patients with no improvement (OR: 0.32, 95% CI: 0.13–0.75). Over a six-month period, mean OP visits were significantly lower in seizure-free patients (2.27 times) than in those with seizure reduction (3.00 times) and those with no improvement (4.08 times). Mean hospitalizations over 12months among the three groups were 0.03, 0.24, and 0.14 times, respectively. For persistent seizures, 50% received only conventional antiepileptic drugs (AEDs). When epilepsy treatments are considered for their costs and effectiveness, utilities and healthcare use, conditional on seizure control status, can be applied for further analyses.

Age-Specific 18F-FDG Image Processing Pipelines and Analysis Are Essential for Individual Mapping of Seizure Foci in Pediatric Patients with Intractable Epilepsy.

18F-FDG PET is an important tool for the presurgical assessment of children with drug-resistant epilepsy. Standard assessment is performed visually and is often subjective and highly user-dependent. Voxelwise statistics can be used to remove user-dependent biases by automatically identifying areas of significant hypo- or hypermetabolism associated with the epileptogenic area. In the clinical setting, this analysis is performed using commercially available software. These software packages suffer from two main limitations when applied to pediatric PET data: pediatric scans are spatially normalized to an adult standard template, and statistical comparisons use an adult control dataset. The aim of this work was to provide a reliable observer-independent pipeline for the analysis of pediatric 18F-FDG PET scans, as part of presurgical planning in epilepsy. Methods: A pseudocontrol dataset (19 subjects 6–9 y old, and 93 subjects 10–20 y old) was used to create two age-specific 18F-FDG PET pediatric templates in standard pediatric space. The 18F-FDG PET scans of 46 epilepsy patients (16 patients 6–9 y old, and 30 patients 10–17 y old) were retrospectively collated and analyzed using voxelwise statistics. This procedure was implemented with the standard pipeline available in the commercial software Scenium and an in-house Statistical Parametric Mapping, version 8 (SPM8), pipeline (including age-specific pediatric templates and reference database). A κ-test was used to assess the level of agreement between the findings of voxelwise analyses and the clinical diagnosis of each patient. The SPM8 pipeline was further validated using postsurgical seizure-free patients. Results: Improved agreement with the clinical diagnosis was reported using SPM8, in terms of focus localization, especially for the younger patient group: κ = 0.489 for Scenium versus 0.826 for SPM. The proposed pipeline also showed a sensitivity of about 70% in both age ranges for the localization of hypometabolic areas on pediatric 18F-FDG PET scans in postsurgical seizure-free patients. Conclusion: We showed that by creating age-specific templates and using pediatric control databases, our pipeline provides an accurate and sensitive semiquantitative method for assessing the 18F-FDG PET scans of patients under 18 y old.

Treatment of epilepsy in multiple sclerosis

PurposeThe prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden. MethodWe retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017. ResultsWe identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0–80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects. ConclusionSeizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS.

Morphometric MRI features and surgical outcome in patients with epilepsy related to hippocampal sclerosis and low intellectual quotient

ObjectiveThe objectives of this study were to verify in a series of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) if those with low intellectual quotient (IQ) levels have more extended areas of atrophy compared with those with higher IQ levels and to analyze whether IQ could be a variable implicated on a surgical outcome. Material and methodsPatients (n=106) with refractory MTLE-HS submitted to corticoamygdalohippocampectomy (CAH) (57 left mesial temporal lobe epilepsy (MTLE); 45 males) were enrolled. To determine if the IQ was a predictor of seizure outcome, totally seizure-free (SF) versus nonseizure-free (NSF) patients were evaluated. FreeSurfer was used for cortical thickness and volume estimation, comparing groups with lower (<80) and higher IQ (90–109) levels. ResultsIn the whole series, 42.45% of patients were SF (Engel Class 1a; n=45), and 57.54% were NSF (n=61). Total cortical volume was significantly reduced in the group with lower IQ (p=0.01). Significant reductions in the left hemisphere included the following: rostral middle frontal (p=0.001), insula (p=0.002), superior temporal gyrus (p=0.003), thalamus (p=0.004), and precentral gyrus (p=0.02); and those in the right hemisphere included the following: rostral middle frontal (p=0.003), pars orbitalis (p=0.01), and insula (p=0.02). Cortical thickness analysis also showed reductions in the right superior parietal gyrus in patients with lower IQ. No significant relationship between IQ and seizure outcome was found. ConclusionsThis is the first study of a series of patients with pure MTLE-HS, including those with low IQ and their morphometric magnetic resonance imaging (MRI) features using FreeSurfer. Although patients with lower intellectual scores presented more areas of brain atrophy, IQ was not a predictor of surgical outcome. Therefore, when evaluating seizure follow-up, low IQ in patients with MTLE-HS might not contraindicate resective surgery.