Outcome after cortico-amygdalo-hippocampectomy in patients with temporal lobe epilepsy and normal MRI

RationaleWe describe seizure and neuropsychological outcome obtained after CAH in patients with TLE and normal MRI evaluated in the modern imaging era.MethodsForty-five adult consecutive patients with TLE and normal MRI were studied. All patients had neuropsychological testing, interictal and ictal EEG recordings and MRI. They were divided into two groups: Group 1 (n = 18), included patients in whom non-invasive neurophysiological evaluation was lateralizing and Group 2 (n = 27) included patients with non-lateralizing neurophysiological data who were submitted to invasive recordings.ResultsSeventy-seven percent of the Group 1 patients were rated as Engel I; 11% were rated as Engel II and 11% as Engel III. In Group 2, there were 57% of patients seizure-free, 26% in Engel II and 14% in Engel III. Pre-operatively, mean general IQ was 82 and 78 in Groups1 and 2, respectively; post-operatively, mean general IQ was respectively 86 and 71. Some degree of verbal memory decline was noted in all patients submitted to dominant temporal lobe resection in both Groups 1 and 2. At last follow-up visit, 22% of Group 1 and 11% of Group 2 patients were receiving no antiepileptic drugs (AED).ConclusionsOur data showed that patients with TLE and normal MRI could get good surgical results after CAH although 60% of them would need invasive recordings and their results regarding seizure control and cognition were worse than those obtained in patients with MRI defined temporal lobe lesions. Caution should be taken in offering dominant temporal lobe resection to this subset of patients.     

Cognition in patients with benign epilepsy with centrotemporal spikes: A study with long-term VEEG and RS-fMRI

ObjectiveThe purpose of this study was to investigate the relationship between alterations of functional brain network and cognition in patients with benign epilepsy with centrotemporal spikes (BECTS) as a function of spike-wave index (SWI) during slow wave sleep.MethodsResting-state functional magnetic resonance imaging (RS-fMRI) data and Intelligence Quotient (IQ) were collected from two groups of patients with BECTS, including a SWI < 50% group (5 cases) and a SWI ≥ 50% group (7 cases). The SWI was calculated from the long-term video-electroencephalogram monitoring (one sleep cycle was included at least). The RS-fMRI data were analyzed by regional homogeneity (ReHo) method.ResultsThere were three main findings. Firstly, Full Intelligence Quotient (FIQ), Verbal Intelligence Quotient (VIQ), and Performance Intelligence Quotient (PIQ) of the SWI ≥ 50% group were significantly lower than SWI < 50% group (p < 0.05). Secondly, there was a negative correlation between the FIQ, VIQ, PIQ, and SWI (p < 0.05), and the FIQ, VIQ, and PIQ were not dependent on age, age of onset, disease course, years of education, and total number of seizures (p > 0.05). Finally, compared with the SWI < 50% group, the SWI ≥ 50% group showed increased ReHo in the bilateral precentral gyrus, bilateral premotor area, bilateral subcortical structure, right temporal lobe, and bilateral insular lobe, while they showed decreased ReHo in the posterior cingulate cortex and posterior of right inferior temporal lobe.ConclusionsThe alterations of functional brain network caused by the frequent discharges during slow wave sleep could affect cognition in patients with BECTS.     

Memory for public events in patients with unilateral temporal lobe epilepsy

Memory for public events (PEs) was assessed as a marker of remote declarative memory in 36 patients with temporal lobe epilepsy (TLE) and compared with that of 19 patients with extra-TLE (ETLE), 17 patients with idiopathic generalized epilepsy (IGE), and 23 healthy volunteers. Verbal IQ, inventory-based evidence of depression, handedness, onset of illness, disease duration, and medication were obtained. Memory for PEs was reduced in all patient groups (TLE, P < 0.0001; ETLE, P = 0.009; IGE, P = 0.008). The TLE group showed reduced memory for PEs compared with the other patients with epilepsy (P = 0.001). A time gradient was observed, with worse memory for PEs of the 1990s and for PEs that occurred after onset of illness. Our data support the key role of the temporal lobe in remote declarative memory. With patients with TLE remembering fewer PEs from the period after onset of epilepsy, the deficits can be partly attributed to unsuccessful consolidation rather than retrieval difficulties alone.     

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.     

T2 hyperintense signal in patients with temporal lobe epilepsy with MRI signs of hippocampal sclerosis and in patients with temporal lobe epilepsy with normal MRI

BackgroundIncreased MRI T2 signal is commonly present not only in the hippocampus but also in other temporal structures of patients with temporal lobe epilepsy (TLE), and it is associated with histological abnormalities related to the epileptogenic lesion.ObjectiveThis study aimed to verify the distribution of T2 increased signal in temporal lobe structures and its correlations with clinical characteristics of TLE patients with (TLE-HS) or without (TLE-NL) MRI signs of hippocampal sclerosis.MethodsWe selected 203 consecutive patients: 124 with TLE-HS and 79 with TLE-NL. Healthy controls (N = 59) were used as a comparison group/comparative group. T2 multiecho images obtained via a 3-T MRI were evaluated with in-house software. T2 signal decays were computed from five original echoes in regions of interest in the hippocampus, amygdala, and white matter of the anterior temporal lobe. Values higher than 2 standard deviations from the mean of controls were considered as abnormal.ResultsT2 signal increase was observed in the hippocampus in 78% of patients with TLE-HS and in 17% of patients with TLE-NL; in the amygdala in 13% of patients with TLE-HS and in 14% of patients with TLE-NL; and in the temporal lobe white matter in 22% of patients with TLE-HS and in 8% of patients with TLE-NL. Group analysis demonstrated a significant difference in the distribution of the T2 relaxation times of the hippocampus (ANOVA, p < 0.0001), amygdala (p = 0.003), and temporal lobe white matter (p < 0.0001) ipsilateral to the epileptogenic zone for patients with TLE-HS compared with controls but only for the amygdala (p = 0.029) and temporal lobe white matter (ANOVA, p = 0.025) for patients with TLE-NL compared with controls. The average signal from the hippocampus ipsilateral to the epileptogenic zone was significantly higher in patients with no family history of epilepsy (two-sample T-test, p = 0.005).ConclusionIncreased T2 signal occurs in different temporal structures of patients with TLE-HS and in patients with TLE-NL. The hippocampal hyperintense signal is more pronounced in patients without family history of epilepsy and is influenced by earlier seizure onset. These changes in T2 signal may be associated with structural abnormalities related to the epileptogenic zone or to the nature of the initial precipitating injury in patients with TLE.     

The executive profile of children with Benign Epilepsy of Childhood with Centrotemporal Spikes and Temporal Lobe Epilepsy

RationaleBenign Epilepsy of Childhood with Centrotemporal Spikes (BECTS) and temporal lobe epilepsy (TLE) represent two distinct models of focal epilepsy of childhood. In both, there is evidence of executive dysfunction. The purpose of the present study was to identify particular deficits in the executive function that would distinguish children with BECTS from children with TLE.MethodsWe prospectively evaluated 19 consecutive children and adolescents with TLE with hippocampal sclerosis (HS) (57.9% male; mean 11.74 years [SD 2.05]; mean IQ 95.21 [SD 15.09]), 19 with BECTS (36.8% male; mean 10.95 years [SD 2.33]; mean IQ 107.40 [SD 16.01]), and 21 age and gender-matched controls (33.3% male; mean 11.86 years [SD 2.25]; mean IQ 108.67 [15.05]). All participants underwent a neuropsychological assessment with a comprehensive battery for executive and attentional functions. We used ANOVA and chi-square to evaluate differences on demographic aspects among groups (BECTS, TLE-HS, and control groups). Group comparisons on continuous variables were complemented by MANOVA and Bonferroni posthoc comparisons.ResultsPatients with BECTS had worse performance than controls in: Matching Familiar Figures Test, time (p = 0.001); Matching Familiar Figures Test, time × errors index (p < 0.001); Verbal Fluency for foods (p = 0.038); Trail Making Test, part B time (p = 0.030); Trail Making Test, part B number of errors (p = 0.030); and WCST, number of categories achieved (p = 0.043). Patients with BECTS had worse performance than patients with TLE-HS on Matching Familiar Figures Test, time (p = 0.004), and Matching Familiar Figures Test, time × errors index (p < 0.001). Patients with TLE-HS had worse performance than controls on the following tests: Verbal Fluency for foods (p = 0.004); Wisconsin Card Sorting Test, the number of categories achieved (p < 0.001); and Wisconsin Card Sorting Test, the number of perseverative errors (p = 0.028). Patients with TLE-HS had worse performance than patients with BECTS on Digit Backward (p = 0.002); and the Wisconsin Card Sorting Test, the number of perseverative errors (p < 0.001).ConclusionsPatients with TLE and BECTS present distinct cognitive profiles. Patients with TLE-HS had worse performance in mental flexibility, concept formation, and working memory compared to BECTS. Patients with BECTS had worse inhibitory control compared to children with TLE-HS. Both TLE-HS and BECTS had a higher number of errors on an inhibitory control test. However, patients with BECTS had a slower mental processing even when compared to patients with TLE-HS. Rehabilitation programs for children with epilepsy must include children with benign epilepsies and must take into account the epileptic syndrome and its particular neurocognitive phenotype.     

Impaired cerebral blood flow networks in temporal lobe epilepsy with hippocampal sclerosis: A graph theoretical approach

Graph theory is an emerging method to investigate brain networks. Altered cerebral blood flow (CBF) has frequently been reported in temporal lobe epilepsy (TLE), but graph theoretical findings of CBF are poorly understood. Here, we explored graph theoretical networks of CBF in TLE using arterial spin labeling imaging. We recruited patients with TLE and unilateral hippocampal sclerosis (HS) (19 patients with left TLE, and 21 with right TLE) and 20 gender- and age-matched healthy control subjects. We obtained all participants' CBF maps using pseudo-continuous arterial spin labeling and analyzed them using the Graph Analysis Toolbox (GAT) software program. As a result, compared to the controls, the patients with left TLE showed a significantly low clustering coefficient (p = 0.024), local efficiency (p = 0.001), global efficiency (p = 0.010), and high transitivity (p = 0.015), whereas the patients with right TLE showed significantly high assortativity (p = 0.046) and transitivity (p = 0.011). The group with right TLE also had high characteristic path length values (p = 0.085), low global efficiency (p = 0.078), and low resilience to targeted attack (p = 0.101) at a trend level. Lower normalized clustering coefficient (p = 0.081) in the left TLE and higher normalized characteristic path length (p = 0.089) in the right TLE were found also at a trend level. Both the patients with left and right TLE showed significantly decreased clustering in similar areas, i.e., the cingulate gyri, precuneus, and occipital lobe. Our findings revealed differing left–right network metrics in which an inefficient CBF network in left TLE and vulnerability to irritation in right TLE are suggested. The left–right common finding of regional decreased clustering might reflect impaired default-mode networks in TLE.     

Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy

ObjectiveThe aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG).MethodsAccording to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ–mesial MRI-negative TLE or neocortical SOZ–neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology.ResultsThirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p = 0.031) and more seizures without clear lateralization of ictal activity (p = 0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found.ConclusionsAccording to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach.     

Short-term neurocognitive outcomes following anterior temporal lobectomy

Changes in cognitive function are a well established risk of anterior temporal lobectomy (ATL). Deficits in verbal memory are a common postoperative finding, though a small proportion of patients may improve. Postoperative evaluation typically occurs after six to 12 months. Patients may benefit from earlier evaluation to identify potential needs; however, the results of a formal neuropsychological assessment at an early postoperative stage are not described in the literature. We compared pre- and postoperative cognitive function for 28 right ATL and 23 left ATL patients using repeated measures ANOVA. Changes in cognitive function were compared to ILAE seizure outcome. The mean time to postoperative neuropsychological testing was 11.1 weeks (SD = 6.7 weeks). There was a side × surgery interaction for the verbal tasks: immediate memory recall (F(1,33) = 20.68, p < 0.001), short delay recall (F(1,29) = 4.99, p = 0.03), long delay recall (F(1,33) = 10.36, p = 0.003), recognition (F(1,33) = 5.69, p = 0.02), and naming (F(1,37) = 15.86, p < 0.001). This indicated that the left ATL group had a significant decrement in verbal memory following surgery, while the right ATL group experienced a small but significant improvement. For the right ATL group, there was a positive correlation between ILAE outcome and improvement in immediate recall (r = − 0.62, p = 0.02) and long delay recall (r = − 0.57, p = 0.03). There was no similar finding for the left ATL group. This study demonstrates that short-interval follow-up is effective in elucidating postoperative cognitive changes. Right ATL was associated with improvement in verbal memory, while left ATL resulted in a decrement in performance. Improvement in the right ATL group was related to improved seizure outcome. Short-interval follow-up may lend itself to the identification of patients who could benefit from early intervention.     

Preoperative IQ predicts seizure outcomes after anterior temporal lobectomy

PurposeIQ tests are frequently used in the preoperative neuropsychological assessment of candidates for anterior temporal lobectomy (ATL). We reviewed IQ test results and surgery outcomes to evaluate the roles of IQ tests in the preoperative work-up.MethodsA total of 205 adult patients who had undergone ATL and whose seizure outcomes were followed for 2 years after surgery were included. The short form WAIS-R was used to estimate intelligence. Multiple linear regression and logistic regression analyses were used to examine the variables for IQ and seizure outcomes.ResultsEducation, duration of epilepsy and gender were factors that accounted for 24.6% of the variance in the full-scale IQ (FSIQ) scores. The verbal IQ and performance IQ discrepancies at various magnitudes could not lateralize the seizure foci. Freedom of seizure was noted in 128 (62.4%) of the patients. Seizure outcomes, however, correlated with the preoperative FSIQ. After adjustment for variables that affect seizure outcomes, the FSIQ was an independent predictor of postoperative seizure outcomes (OR 1.04, 95% CI 1.01–1.06, p = 0.003). Of patients who had FSIQ lower than 70, 50% became free from seizures by 2 years after surgery.ConclusionsIn our study, IQ tests were unable to lateralize seizure foci but may serve as an independent predictor of postoperative seizure outcomes. Since a longer duration of epilepsy had deleterious effects on intelligence, earlier surgical intervention might better preserve neuropsychological function and, consequently, allow better seizure control after ATL. Nonetheless, patients with lower IQ scores could still benefit from ATL.     

Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy

ObjectiveThe goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI).MethodsA fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided.ResultsA fearful face paradigm led to significant amygdalar activation in all but one patient (p < 0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipislateral amygdalar fMRI-responses.ConclusionUnilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.     

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.     

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.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Reduced Pumilio-2 expression in patients with temporal lobe epilepsy and in the lithium–pilocarpine induced epilepsy rat model

ObjectiveDrosophila Pumilio (Pum), a homolog of mammalian Pum2, plays an important role in translational regulation in the central nervous system (CNS), particularly for dendrite outgrowth and neuronal excitability. We investigated the expression pattern and cellular distribution of Pum2 in patients with drug-refractory temporal lobe epilepsy (TLE) and rats with lithium chloride–pilocarpine-induced epilepsy.MethodsReal-time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, and double-labeled immunofluorescence were utilized to determine the expression level and distribution of Pum2 in temporal neocortex tissues from patients with intractable TLE (n = 20) and patients with severe head trauma (n = 20) in addition to the hippocampus and adjacent cortex of rats with lithium chloride–pilocarpine-induced TLE and controls.ResultsPum2 was expressed in the cell bodies and dendrites of neurons but did not colocalize with glial fibrillary acidic protein-positive astrocytes or propidium iodide (PI) in nuclei. The expression of Pum2 was significantly reduced in patients and rats with TLE in comparison to controls (P < 0.05).ConclusionPum2 expression was less in patients with TLE and a rodent model of epilepsy, suggesting that decreased expression of Pum2 may be involved in the pathogenesis of TLE.     

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy

ObjectiveTemporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance.MethodsThirty-four patients (right TLE = 17, left TLE = 17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests.ResultsThe number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume.ConclusionIn patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity.     

Psychiatric disorders in temporal lobe epilepsy: An overview from a tertiary service in Brazil

PurposeTo evaluate the frequency and intensity of psychiatric disorders in a group of temporal lobe epilepsy (TLE) patients from a tertiary-care center.MethodsClinical and sociodemographic data of 73 patients were collected and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured clinical interview (MINI-PLUS), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Brief Psychiatric Rating Scale (BPRS).ResultsPatients with TLE showed a high frequency of lifetime psychiatric disorders (70%), the most frequent being mood disorders (49.3%). At assessment, 27.4% of the patients were depressed and 9.6% met criteria for bipolar disorder. Nevertheless, depression had not been properly diagnosed nor treated. Anxiety disorders were also frequent (42.5%), mainly generalized anxiety disorder (GAD) (21.9%). Obsessive compulsive disorder (OCD) was present in 11.0% and psychotic disorders in 5.5% of the sample. Patients with left mesial temporal sclerosis (LMTS) exhibited more psychopathologic features, mainly anxiety disorders (p = 0.006), and scored higher on HAM-A and HAM-D (p < 0.05 in both).ConclusionTLE is related to a high frequency of psychiatric disorders, such as anxiety and depression, which are usually underdiagnosed and undertreated. Damage to the left mesial temporal lobe, seen in LMTS, seems to be an important pathogenic lesion linked to a broad range of psychopathological features in TLE, mainly anxiety disorders. The present study prompts discussion on the recognition of the common psychiatric disorders in TLE, especially on the Brazilian setting.     

Correlation between interictal cerebral glucose hypometabolism and IQ in children with epilepsy

The aim of this study was to understand the relationship between IQ and glucose metabolism in brain cells in a wide variety of subjects with epilepsy. The study participants were 78 children with epilepsy and 15 healthy children for comparison. All participants were administered the Chinese Wechsler Intelligence Scale for Children (C-WISC). The verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full-scale intelligence quotient (FIQ) were compared between children with epilepsy and typically developing children. Seventy-eight patients underwent interictal positron emission computed tomography (PET) using 2-deoxy-2[¹⁸F]fluoro-d-glucose (FDG) as the tracer for evaluating brain glucose metabolism. Verbal intelligence quotient, PIQ, and FIQ based on the C-WISC were significantly lower in children with epilepsy than those in the healthy comparison group (P < 0.001, P = 0.001, and P < 0.001, respectively). The IQ of patients with normal metabolism, unifocal abnormal hypometabolism, and multifocal abnormal hypometabolism determined by PET differed significantly. The extent of the abnormal hypometabolism was negatively correlated with the FIQ (rs = − 0.549, P < 0.001). In patients with lateralized hypometabolism based on PET, the VIQ/PIQ discrepancy scores (|VIQ − PIQ| ≥ 15 points) differed significantly between the left hemisphere abnormal hypometabolism and right hemisphere abnormal hypometabolism subgroups, with negative values in the left and positive values in the right subgroups (P = 0.004). In conclusion, brain metabolic abnormalities are correlated with IQ, and performing interictal PET along with C-WISC can better assess the extent of severity of cognitive impairment and VIQ/PIQ discrepancy.     

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.     

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.