Patterns of verbal learning and memory in children with intractable temporal lobe or frontal lobe epilepsy

PurposeThe objective of this study was to provide a better understanding of the verbal learning and memory (VLM) patterns that might differentiate children with frontal lobe epilepsy (FLE) from children with temporal lobe epilepsy (TLE) and to examine the impact of variables thought to influence outcomes (seizure laterality, age at seizure onset, age at assessment, epilepsy duration, number of antiepileptic drugs).MethodsRetrospective analyses were carried out for children with intractable unilateral TLE (n = 100) and FLE (n = 27) who completed standardized measures of VLM entailing lists of single words or lists of word pairs.ResultsMean intelligent quotients and VLM scores on single words fell within the average range for both groups, whereas scores fell within the low average to borderline range on word pairs. No significant overall differences in VLM were found between the group with TLE and the group with FLE.Older age at assessment and older age at seizure onset were generally associated with better VLM in both groups but were related to better performance in a number of indices in the group with TLE and only fewer intrusions in the group with FLE.ConclusionsThe VLM profiles of children with TLE and FLE are generally similar. Older age at assessment and older age at seizure onset have a favorable impact on both groups but are related to better encoding, retrieval, and monitoring processes for the group with TLE and improved memory monitoring (i.e., as indicated by fewer intrusions) in the group with FLE.     

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PurposeEpilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe.MethodsWe systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies.ResultsOverall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60 months, range 12–72); six patients (35.3%) were seizure free at least 12 month before observation points (median duration 120.5 months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p = 0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p = 0.116) and before reoperation (p = 0.622) was not poorer compared to patients with congruent Video-EEG results.ConclusionsReoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.     

Postsurgical outcome in patients with auditory auras and drug-resistant epilepsy

PurposeWe assessed whether patients with auditory auras have similar outcomes after epilepsy surgery as patients without auditory auras, and hypothesized that patients with non-dominant hemisphere foci might fare better after temporal lobe surgery than patients with dominant resections.MethodsIn this retrospective study, outcome after temporal resection was assessed for patients with drug-resistant epilepsy. Preoperative demographic data, clinical data, and surgical outcome were prospectively registered in a database from 1986 through 2016. Seizure outcome was classified as either seizure-free or relapsed.ResultsData were available in 1186 patients. Forty five patients (3.8%) reported auditory auras; 42 patients (93%) had temporal lobe epilepsy (TLE), and three patients (7%) had extratemporal epilepsy. Since most patients with auditory auras had TLE and in order to have comparable groups, we selected 41 patients with auditory auras and compared them with patients without auditory auras who had temporal lobe resections (767 patients). There were no significant demographic or clinical differences between TLE patients with auditory auras and those without. Patients who had auditory auras were more likely to relapse after temporal lobe surgery than those without (p = 0.03). Among patients who had auditory auras and temporal lobe surgery, side of surgery was not related to postoperative outcome (p = 0.3).ConclusionAuditory auras are rare among patients with drug-resistant TLE. The presence of an auditory aura in a patient with drug-resistant TLE carries a worse prognosis for a postoperative seizure free outcome and this is not related to the side of surgery.     

Clinical factors associated with postictal headache in Chinese patients with partial epilepsy

PurposeTo investigate the incidence of postictal headache (PIH) and the factors potentially related to the occurrence of PIH in a Chinese epileptic center.MethodsConsecutive adult patients with epilepsy, referred to the outpatient clinic of the Epilepsy Center of the PLA General Hospital between February 01, 2012, and May 10, 2013, were recruited to this study. 854 patients with partial epilepsy completed a questionnaire regarding headache, 466 patients with temporal lobe epilepsy (TLE), 82 patients with occipital lobe epilepsy (OLE) and 306 patients with frontal lobe epilepsy (FLE). A semi-structured interview was performed in those who confirmed headache.ResultsPIH occurred in 328 (38.41%) of the subjects. By type of epilepsy, PIH was found in 164 (35.19%) of the patients with TLE, 46 (56.01%) of the patients with OLE, and 118 (38.56%) of the patients with FLE. The incidence of PIH in OLE was significantly higher than in TLE and FLE (P < 0.05). It occurs more frequently after generalized tonic–clonic seizures than other seizure types. Logistic regression analysis revealed that age at onset, type of seizure and classification of epilepsy were each significantly related to the occurrence of PIH.ConclusionThe results of our study revealed possible relationships between PIH and the region of epileptic focus and area of spread of epileptic discharges.     

Stigma accounts for depression in patients with epilepsy

ObjectiveEpilepsy is a chronic disease with an increased risk of stigmatization due to psychosocial consequences of the seizures. Intuitively, one may well conclude that stigmatization would lead to depression in patients with epilepsy as well as in other patient groups with increased risk of stigmatization. Indeed, there are a few studies in support of this intuition. In this study, we aimed to investigate the relationship between level of stigmatization and the severity of the depressive symptoms in our patients with epilepsy.MethodsThis is a substudy of our main study, which aimed to develop a scale for the quantification of the stigma level in patients with epilepsy. The study included a total of 302 patients with epilepsy, who had at least a literacy level education and one-week-seizure-freedom. Beck Depression Inventory (BDI) was used to quantify depressive symptoms. The correlation between BDI scores and the Stigma Scale for Epilepsy-Self Report (SSE-SR) scores was evaluated. A regression analysis was done in order to parse out significant sociodemographic and clinical factors contributing to depressive symptoms. Statistical analyses were done using the Statistics Package for the Social Sciences software 24.0 package program.ResultsWe saw that 46.9% (n = 139) of this population rated themselves as having at least mildly depressive symptoms with BDI (BDI > 9). There was a moderate positive correlation between stigma scores and BDI scores (p = 0.000, r = 0.504), and 96.3% of highly stigmatized patients had at least mildly depressive scores, 73.9% of the nonstigmatized group had none or minimal depressive scores. Stigma scores (β = .51), gender, educational level, seizure frequency, and income level were the variables significantly affecting the BDI scores. Stigma score accounted for 26.2% of the variance in the BDI score.ConclusionThis study shows that stigmatization of the patients with epilepsy leads to depression in those patients. Therefore, protection of the patients with epilepsy against stigmatization may also help to protect them from a concomitant disabling condition. On the other hand, detection for depressive symptoms in already stigmatized patients with epilepsy may unearth a treatable condition.     

Intracranial EEG seizure onset patterns in unilateral temporal lobe epilepsy and their relationship to other variables

ObjectiveWe performed a retrospective study to determine the different types of seizure onset patterns (SOP) in invasive EEG (IEEG) in patients with temporal lobe epilepsy (TLE).MethodsWe analyzed a group of 51 patients (158 seizures) with TLE who underwent IEEG. We analyzed the dominant frequency during the first 3 s after the onset of ictal activity. The cut-off value for distinguishing between fast and slow frequencies was 8 Hz. We defined three types of SOPs: (1) fast ictal activity (FIA) – frequency ?8 Hz; (2) slow ictal activity (SIA) – frequency <8 Hz; and (3) attenuation of background activity (AT) – no clear-cut rhythmic activity during the first 3 s associated with changes of IEEG signal (increase of frequency, decrease of amplitude). We tried to find the relationship between different SOP types and surgery outcome, histopathological findings, and SOZ localization.ResultsThe most frequent SOP was FIA, which was present in 67% of patients. More patients with FIA were classified postoperatively as Engel I than those with SIA and AT (85% vs. 31% vs. 0) (P < 0.001). There were no statistically significant differences in the type of SOP, in the histopathological findings, or in the SOZ localization.ConclusionIn patients with refractory TLE, seizure onset frequencies ?8 Hz during the first 3 s of ictal activity are associated with a better surgical outcome than frequencies <8 Hz.SignificanceOur study suggests that very early seizure onset frequencies in IEEG in patients with TLE could be the independent predictive factor for their outcome, regardless of the localization and etiology.     

Clinical relevance of source location in frontal lobe epilepsy and prediction of postoperative long-term outcome

PurposeTo evaluate the value of magnetoencephalography (MEG) source localization in localization of epileptic activities and predicting surgical outcome in frontal lobe epilepsies (FLE).MethodsForty-six patients with presurgical MEG evaluation and intractable FLE surgery (28 male patients) were analyzed retrospectively with a mean follow-up of 5 years. Dipole analysis was performed for MEG source imaging (MSI). The localization of dipole clusters in relation to the dominant hemisphere, lesions, resection cavity and functional cortex were analyzed. The predictive value of MSI in respect to clinical outcome with long-term postoperative follow up was evaluated.ResultsInterictal focal epileptic activities were found in 82.6% (38/46) patients with monofocal activity 81.6% (31/38) and multifocal activities 18.4% (7/38). Seizure free rate was 47.9% at the mean follow-up of 5.0 ± 4.0 years (median 11.5, range 2–57). Seizure recurrence mainly occurred in the first 1 year after surgery. In the monofocal epileptic activity group, 58.1% (18/31) of the patients were seizure free, predicitng postoperative seizure freedom better than multifocal localization 0% (0/7) (p = 0.028). Dipole clusters were completely resected in 70.9% of monofocal activity patients, which had higher seizure free rates compared to partial resection (p = 0.002). In patients with surgery in the dominant hemisphere, seizure control was less likely (p = 0.006).ConclusionMSI contributes to the clinical prediction of postoperative outcome in FLE patients. MSI may non-invasively disclose early epileptogenic lesions, pointing to a resectable lesion, and it then facilitates shortcut route of presurgical evaluation.     

White matter integrity correlates with depressive symptomatology in temporal lobe epilepsy

RationaleWhite matter abnormalities occur in both temporal lobe epilepsy (TLE) and depression, but there is limited research examining the depression–white matter association in depressed individuals with TLE. This study examined the relationship between white matter integrity (WMI) and depression including the influence of age at seizure onset, in adults with TLE, TLE and depression, and depression only.MethodsThirty-one adults were in one of three groups: TLE without depression (TLE; n = 11), TLE with depression (TLE + DEP; n = 9), and depression without TLE (DEP; n = 11). Participants completed structured interviews for depression diagnosis and severity. White matter integrity was estimated based on fractional anisotropy (FA) calculated in frontotemporolimbic (FTL) and non-FTL regions in the JHU DTI atlas.ResultsIn adults with TLE (n = 20), depressive symptomology was significantly correlated with FA in non-FTL regions and trended toward significance in FTL regions. These associations were found in FTL (statistically significant) and non-FTL (trended toward significance) regions in participants with childhood seizure onset but not in those with adolescent/adult seizure onset.ConclusionsCurrent results suggest that WMI, within FTL and non-FTL regions, are associated with depressive symptomology in adults with TLE. This association may be most notable in those with childhood-onset epilepsy. These findings could have important implications for the conceptualization and clinical care of neuropsychiatric comorbidities in TLE.     

Heart rate variability in patients with frontal lobe epilepsy

ObjectiveTo identify autonomic dysregulation in frontal lobe epilepsy (FLE).MethodsWe studied 14 male and 11 female subjects with FLE and an equal number of matched healthy control subjects. Lead I electrocardiograms were obtained for 5 min in the interictal state during daytime. Frequency-domain analysis of heart rate variability was performed and the data subsequently converted to heart rate interval and high frequency (HF; 0.15–0.45 Hz) power which representing vagal or parasympathetic regulation, as well as low frequency (LF; 0.04–0.15 Hz) power and LF/(HF + LF) expressed in normalized units (LF%) (considered to mirror sympathetic regulation). Differences in data between groups were compared using t-test.ResultsThe epilepsy group had a lower mean heart rate interval and a lower high frequency power.ConclusionsPatients with FLE have interictally faster heart rates, attributed to lower parasympathetic drive, which may contribute to the higher incidence of sudden death that is seen in this group of patients. This suggests that the mechanism of decreased HRV in patients with FLE is probably different from that in patients with temporal lobe epilepsy.     

Treatment of depression in patients with temporal lobe epilepsy: A pilot study of cognitive behavioral therapy vs. selective serotonin reuptake inhibitors

There is a high prevalence of depression in patients with epilepsy, which negatively impacts their quality of life (QOL) and seizure control. Currently, the first-line of treatment for depression in patients with epilepsy is based on selective serotonin reuptake inhibitors (SSRIs). The main objective of this pilot study was to compare cognitive behavioral therapy (CBT) versus SSRIs for the treatment of major depressive disorder (MDD) in patients with temporal lobe epilepsy (TLE). Seven patients who received group CBT were compared with eight patients treated with SSRIs. All were diagnosed with MDD and TLE. Patients were assessed at baseline before treatment and at six and 12 weeks during treatment with the Quality of Life in Epilepsy Scale of 31 items (QOLIE 31), the Beck Depression Inventory (BDI), and the Hospital Anxiety and Depression Scale (HADS). Seizure records were also taken on a monthly basis. After 12 weeks of treatment, both groups showed improved QOL and reduced severity of depression symptoms. There were no statistically significant group differences in the final scores for the BDI (p = 0.40) and QOLIE 31 (p = 0.72), although the effect size on QOL was higher for the group receiving CBT. In conclusion, the present study suggests that both CBT and SSRIs may improve MDD and QOL in patients with TLE. We found no significant outcome differences between both treatment modalities. These findings support further study using a double-blind controlled design to demonstrate the efficacy of CBT and SSRIs in the treatment of MDD and QOL in patients with TLE.     

Major depressive disorder as a predictor of a worse seizure outcome one year after surgery in patients with temporal lobe epilepsy and mesial temporal sclerosis

PurposeThe association between pre-surgical psychiatric disorders (PDs) and worse seizure outcome in patients with refractory epilepsy submitted to surgery has been increasingly recognized in the literature. The present study aimed to verify the impact of pre- and post-surgical PD on seizure outcome in a series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE–MTS).MethodData from 115 TLE–MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy (CAH) were analyzed. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV and ILAE criteria. The outcome subcategory Engel IA was considered as corresponding to a favorable prognosis. A multivariate logistic regression model was applied to identify possible risk factors associated with a worse seizure outcome.ResultsPre-surgical PDs, particularly major depressive disorder (MDD), anxiety and psychotic disorders, were common, being found in 47 patients (40.8%). Fifty-six patients (48.7%) were classified as having achieved an Engel IA one year after CAH. According to the logistic regression model, the presence of pre-surgical MDD (OR = 5.23; p = 0.003) appeared as the most important risk factor associated with a non-favorable seizure outcome.ConclusionAlthough epilepsy surgery may be the best treatment option for patients with refractory TLE–MTS, our findings emphasize the importance of performing a detailed psychiatric examination as part of the pre-surgical evaluation protocol.     

Severity of depressive symptomatology and functional impairment in children and adolescents with temporal lobe epilepsy

ObjectiveDepression is a frequent psychiatric disorder in children with temporal lobe epilepsy (TLE). However, severity of depressive symptoms (DS) is frequently neglected in these patients. This study aimed to determine severity of DS and global functioning by using quantitative measures and to establish their correlation with patients’ demographics and clinical variables.Methods31 children (mean age of 11.8 ± 2.3 years) with TLE were assessed with K-SADS-PL for axis I DSM-IV diagnosis. Severity of DS was measured by Children Depression Rating Scale-Revised – CDRS-R. Global functional impairment was evaluated with Child Global Assessment Scale-CGAS.Results25 patients (56% boys; 12 ± 2.3 years) had current DS, moderate or severe in 84% according to CDRS-R T-Score. Severity of DS was not correlated with age (p = 0.377), gender (p = 0.132), seizure control (p = 0.936), age of onset (p = 0.731), duration of epilepsy (p = 0.602) and the presence of hippocampal sclerosis (p = 0.614). Patients had moderate to major functional impairment measured by CGAS (48.7 ± 8.8), being adolescents more impaired than children (p = 0.03). Impairment of global functioning was not associated with epilepsy variables (p > 0.05).ConclusionChildren with TLE had moderate to severe DS early in the course of their disease with a relevant impact on their global functional activities, especially considering adolescents. Epilepsy severity seems not to be correlated to the severity of DS, contradicting the idea of a cause–consequence relationship. More systematic research is needed to better understand the association of depressive disorders in children and adolescents with TLE.     

The relationship of seizure focus with depression,anxiety, and health-related quality of life in children and adolescents with epilepsy

For youth with epilepsy, comorbid psychiatric conditions, such as depression and anxiety, require further examination as they carry increased risk for reduced health-related quality of life (HRQOL). The current study assessed whether rates of depression, anxiety, and withdrawal behaviors differed based on seizure location. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 132 children and adolescents (mean age = 11.34, SD = 3.95) with generalized or partial (i.e., frontal [FLE] or temporal lobe epilepsy [TLE]) epilepsy. Our results identified clinically significant internalizing psychopathology in nearly half of our sample (41%). Although rates of internalizing behavior were similar between generalized and partial groups, children and adolescents with TLE demonstrated higher rates of depression compared to youth with FLE. No effects of laterality on internalizing behaviors were identified between TLE and FLE groups. Finally, for youth with TLE, parental depression ratings along with current number of antiepileptic medications (AEDs) were found to be significant barriers to HRQOL above and beyond anxiety, withdrawal, and epilepsy-specific variables. Temporal lobe epilepsy was associated with a two-fold risk of clinically significant depression ratings. These findings highlight the high prevalence of internalizing psychopathology features in pediatric epilepsy and offer further support for the relationship between depression and TLE in children and adolescents with epilepsy.     

Effect of successful epilepsy surgery on subjective and objective sleep parameters – a prospective study

ObjectiveTo evaluate the effect of surgery on subjective and objective measures of sleep quality among patients with medically refractory focal epilepsy.MethodsIn a prospective cohort study, patients with medically refractory epilepsy undergoing epilepsy surgery were recruited. All patients were assessed seven days pre- and three months post-surgery in terms of history pertaining to epilepsy and sleep, Epworth sleepiness score (ESS), one week sleep log and over night polysomnography (PSG).ResultsAmong 17 patients (mean age 18, 11 males), seizure frequency had reduced (p = 0.04) and self reported sleep parameters had significantly improved (reduced total duration of night time sleep, regularity on one week sleep log and ESS (p < 0.05)) three months following epilepsy surgery. Patients with good surgical outcome (n = 12) showed reduced seizure frequency (p = 0.01) and reduced ESS with corresponding reduction in arousal index (AI) (p = 0.02) and increase in total sleep time (p = 0.03), postoperatively. Three patients in the good surgical outcome group showed reduction in apnea–hypopnea index (AHI) from more than five to less than five. There was no significant change either in seizure frequency, self reported clinical parameters or PSG parameters among patients with poor surgical outcome.ConclusionEpilepsy surgery improves subjective sleep parameters in patients with medically refractory epilepsy during the early post operative period. Successful epilepsy surgery may improve objective (PSG documented) sleep quality, sleep architecture and obstructive sleep apnea with resultant reduction in excessive daytime sleepiness.     

Attention deficits in children with epilepsy: Preliminary findings

ObjectiveAttention difficulties are a common clinical complaint among children with epilepsy. We aimed to compare a range of attentional abilities between groups of children with two common epilepsy syndromes, Temporal Lobe Epilepsy (TLE) and Idiopathic Generalized Epilepsy (IGE), and to healthy controls. We also investigated whether epilepsy factors (laterality of seizure focus, epilepsy onset, duration, and severity) were related to attentional abilities.MethodsMultiple dimensions of attention (selective, sustained, and divided attention and attentional control) were assessed directly with standardized neuropsychological measures in 101 children aged 6–16 years (23 children with TLE, 20 with IGE and 58 healthy controls). Attention was also assessed indirectly, via a parent-report measure.ResultsChildren with TLE performed worse than children with IGE (p = 0.013) and healthy controls (p < 0.001) on a test of attentional control, but no between-group differences were apparent on tests of other attentional abilities. Compared to healthy controls, greater attention problems were reported by parents of children with TLE (p = 0.006) and IGE (p = 0.012). Left-hemisphere seizure focus and greater epilepsy severity were associated with poorer attentional control and sustained-divided attention, respectively, but no other epilepsy factors were associated with attentional abilities.SignificanceThese findings suggest that children with localization-related epilepsy, but not generalized epilepsy, may be at risk of deficits in attentional control. Interventions aimed at improving attentional control may be targeted at children with localization-related epilepsy, particularly those with a left-hemisphere seizure focus, who appear to be particularly susceptible to this type of attentional deficit.     

Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy

IntroductionDepression and memory dysfunction significantly impact the quality of life of patients with epilepsy. Current therapies for these cognitive and psychiatric comorbidities are limited. We explored the efficacy and safety of transcranial direct current stimulation (TDCS) for treating depression and memory dysfunction in patients with temporal lobe epilepsy (TLE).MethodsThirty-seven (37) adults with well-controlled TLE were enrolled in a double-blinded, sham-controlled, randomized, parallel-group study of 5 days of fixed-dose (2 mA, 20 min) TDCS. Subjects were randomized to receive either real or sham TDCS, both delivered over the left dorsolateral prefrontal cortex. Patients received neuropsychological testing and a 20-minute scalp EEG at baseline immediately after the TDCS course and at 2- and 4-week follow-up.ResultsThere was improvement in depression scores immediately after real TDCS, but not sham TDCS, as measured by changes in the Beck Depression Inventory (BDI change: − 1.68 vs. 1.27, p < 0.05) and NDDI-E (− 0.83 vs. 0.9091, p = 0.05). There was no difference between the groups at the 2- or 4-week follow-up. There was no effect on delayed or working memory performance. Transcranial direct current stimulation was well-tolerated and did not increase seizure frequency or interictal discharge frequency. Transcranial direct current stimulation induced an increase in delta frequency band power over the frontal region and delta, alpha, and theta band power in the occipital region after real stimulation compared to sham stimulation, although the difference did not reach statistical significance.DiscussionThis study provides evidence for the use of TDCS as a safe and well-tolerated nonpharmacologic approach to improving depressive symptoms in patients with well-controlled TLE. However, there were no changes in memory function immediately following or persisting after a stimulation course. Further studies may determine optimal stimulation parameters for maximal mood benefit.     

Lacosamide in patients with temporal lobe epilepsy: An observational multicentric open-label study

PurposeThe aim of this study was to evaluate the efficacy and tolerability of lacosamide (LCM) both as add-on therapy and monotherapy in patients with temporal lobe epilepsy (TLE) based on an observational, prospective, multicenter study.MethodsWe enrolled 100 patients (mean age: 43.4 ± 12.53 years, 57 females) with nonlesional TLE and TLE with hippocampal sclerosis (HS) that did not respond to the first drug and who were referred to epilepsy centers of the University of Catanzaro, University of Palermo, IRCSS Neuromed of Pozzilli, and Otto-von-Guericke University of Magdeburg. In this open-label, multicenter trial, patients were initiated on oral LCM as add-on therapy to first AED monotherapy or as a later add-on to two concomitant AEDs. Seizure frequency changes and adverse events were recorded for at least six months after LCM was added.ResultsFourteen patients dropped out because of positive MRI findings other than HS. Patients received LCM at 200–400 mg/day. Fifty-eight out of these 86 patients with seizures that were previously drug-resistant had reduced seizure frequency after introduction of LCM. Forty-five out of 86 patients were classified as responders (12 were seizure-free, 33 achieved a reduction > 50%). Interestingly, five patients out of 86 achieved seizure freedom for at least one year and progressively switched to monotherapy with LCM, and all five remained seizure-free at follow-up (6–48 months).ConclusionsOur results may suggest that LCM at doses of 200 to 400 mg/day reduces seizure frequency in adults with TLE regardless of the presence of HS, and that it may be considered as a first add-on treatment for patients with pharmacoresistant TLE.     

IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy

ObjectiveIsocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II–IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency.MethodsThis was a retrospective study. Patients with grades II–IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A — postoperative seizure freedom; Group B — 1–11 seizures over 12 months (less than one seizure per month); and Group C — greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data.ResultsOne hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12 months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p = 0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p = 0.032) and Group B (RR 9.70, p = 0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p = 0.004).SignificanceIn patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy.     

Temporal lobe surgery in medically refractory epilepsy: A comparison between populations based on MRI findings

IntroductionHigh resolution MRI findings suggestive of mesial temporal sclerosis (MRI-MTS) correlate with good outcome after surgery. However, a large group of patients present with normal brain MRI (N-MRI) and temporal lobe epilepsy (TLE). We aim to compare pre-operative ictal EEG patterns in predicting surgical outcomes in the population with MRI-MTS vs. N-MRI after selective anterior-mesial temporal lobe (AMTL) resection.Methods241 patients with unilateral anterior ictal EEG findings underwent selective AMTL resection. 143 MRI-MTS and 98 N-MRI patients were identified. Outcome was based on the modified Engel classification, ictal EEG pattern at seizure onset, demographics and MRI findings.ResultsSeizure-free outcome was seen in the MRI-MTS in 79% of patients, compared to 59.1% (p < .005) of the N-MRI group. No significant difference was identified in ictal EEG patterns at presentation between groups. Class I outcome was achieved in 78.9% of patients that had theta rhythm and MRI-MTS compared to 57.9% of patients that had theta rhythm and N-MRI (p < 0.05).Discussion and conclusionSurgical treatment for mesial TLE is effective. Positive MRI suggestive of mesial temporal sclerosis (MTS) predicts better seizure control after surgery. Theta rhythm is the most common ictal pattern and seems to carry the best prognosis for TLE. However, a well-selected group of patients with N-MRI will benefit from surgical intervention, and similar outcome to MRI-MTS patients can be achieved if delta ictal EEG pattern is presented at initial onset. Early referral to an epilepsy center cannot be emphasized enough, even in situations when high-resolution brain MRI is normal.     

Interleukin-6, interleukin-1 beta and interleukin-1 receptor antagonist levels in epileptic seizures

PurposeData are accumulating to support the involvement of inflammatory mechanisms in the pathogenesis and course of epilepsy.MethodsThe aim of this study was to examine seizure-induced changes in plasma concentrations of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and interleukin-1 beta (IL-1β) in 23 patients with epilepsy undergoing a video-electroencephalography (EEG) study. Patients were divided into groups based on epilepsy type as follows: temporal lobe epilepsy (TLE) (n = 6), extra-temporal lobe epilepsy (XLE) (n = 8) and idiopathic generalised epilepsy (IGE) (n = 9). Serum levels of IL-1β, IL-1Ra and IL-6 were measured at baseline, immediately after the epileptic seizure, and at 3 h, 6 h, 12 h and 24 h after the seizure.ResultsWe demonstrated a significant increase in plasma levels of IL-6 and IL-1Ra that peaked at 12 h into the post-ictal period (p < 0.05). IL-1β levels did not differ from the baseline levels. We did not observe any differences in post-ictal cytokine release patterns between the TLE, XLE and IGE groups.ConclusionThe present study confirms the findings that epileptic seizures induce the production of IL-6 and IL-1Ra.