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

OBJECTIVE: The 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. METHODS: Children 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. RESULTS: Children 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. CONCLUSIONS: Similar 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.     

Long-term postoperative atrophy of contralateral hippocampus and cognitive function in unilateral refractory MTLE with unilateral hippocampal sclerosis

ObjectiveThis study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL).MethodsWe performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals.ResultsThe volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p < 0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median = 8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome.ConclusionsWe observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.     

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.     

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.     

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 there a creative functional paradoxical facilitation in juvenile myoclonic epilepsy?

ObjectiveIn patients with juvenile myoclonic epilepsy (JME), a specific personality profile suggestive of frontal lobe dysfunctions has been described. From a neurobiological point of view, the frontal lobe seems to be crucial for creative processes, although the exact role remains unclear. The theory of creative paradoxical functional facilitation (PFF) assumes that disinhibited frontal lobe function can enhance creative abilities. The aim of the current study was to explore our hypothesis that JME is associated with higher artistic creativity based on the theory of PFF.MethodsWe assessed 25 patients with JME aged 18 to 40 years in regard to neuropsychological creativity testing. Results were compared with those of 25 age-, sex-, and level of education-matched healthy control subjects (HC) and patients with temporal lobe epilepsy (TLE). Creative abilities were assessed using two validated and standardized tests: 1) nonverbal: the incomplete figure task of Torrance Test of Creative Thinking and 2) verbal: verbal creativity test. Additionally, a basic assessment of fluid intelligence (test for problem solving) and frontal lobe function (trail-making test) was administered to all participants.ResultsVerbal creativity was impaired in both groups with epilepsy compared with that in HC (specific score: JME vs. HC, p = 0.008; TLE vs. HC, p = 0.003). In regard to nonverbal creative abilities, both groups with epilepsy exhibited fair performance. Level of fluid intelligence was even in all groups (p = 0.433). Only patients with JME showed deficits in the frontal lobe test of psychomotor speed (time in seconds: 67.7 JME vs. 54.6 TLE vs. 52.8 HC; p = 0.045).ConclusionsOverall, our study did not reveal increased creativity in JME. The current findings provide insights into creative abilities in two different epilepsy syndromes. Knowledge on specific neuropsychological strengths or deficits in patients with epilepsy may be useful for treatment or counseling.     

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.     

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.     

Recognition of facial emotions and identity in patients with mesial temporal lobe and idiopathic generalized epilepsy: An eye-tracking study

PurposeTo describe visual scanning pattern for facial identity recognition (FIR) and emotion recognition (FER) in patients with idiopathic generalized (IGE) and mesial temporal lobe epilepsy (MTLE). Secondary endpoint was to correlate the results with cognitive function.MethodsBenton Facial Recognition Test (BFRT) and Ekman&Friesen series were performed for FIR and FER respectively in 23 controls, 20 IGE and 19 MTLE patients. Eye movements were recorded by a Hi-Speed eye-tracker system. Neuropsychological tools explored cognitive function.ResultsCorrect FIR rate was 78% in controls, 70.7% in IGE and 67.4% (p = 0.009) in MTLE patients. FER hits reached 82.7% in controls, 74.3% in IGE (p = 0.006) and 73.4% in MTLE (p = 0.002) groups. IGE patients failed in disgust (p = 0.005) and MTLE ones in fear (p = 0.009) and disgust (p = 0.03). FER correlated with neuropsychological scores, particularly verbal fluency (r = 0.542, p < 0.001). Eye-tracking revealed that controls scanned faces more diffusely than IGE and MTLE patients for FIR, who tended to top facial areas. A longer scanning of the top facial area was found in the three groups for FER. Gap between top and bottom facial region fixation time decreased in MTLE patients, with more but shorter fixations in bottom facial region. However, none of these findings were statistically significant.ConclusionFIR was impaired in MTLE patients, and FER in both IGE and MTLE, particularly for fear and disgust. Although not statistically significant, those with impaired FER tended to perform more diffuse eye-tracking over the faces and have cognitive dysfunction.     

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.     

Interictal serum brain-derived neurotrophic factor level reflects white matter integrity,epilepsy severity,and cognitive dysfunction in chronic temporal lobe epilepsy

ObjectiveMost patients with temporal lobe epilepsy (TLE) have epileptic foci originating from the medial temporal lobe, particularly the hippocampus. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor mainly expressed in the hippocampus, though it is not known whether the circulating level of BDNF reflects cognitive performance or white matter structural changes in chronic TLE.MethodsThirty-four patients with TLE and 22 healthy controls were enrolled for standardized cognitive tests, diffusion tensor imaging, and serum BDNF measurement. The patients were further divided into a subgroup with unilateral TLE (n = 23) and a subgroup with bilateral TLE (n = 11) for clinical and neuroimaging comparisons.ResultsThere were significantly lower BDNF levels in the patients with TLE compared with the controls, with significance contributed mainly from the subgroup with bilateral TLE, which also had more frequent seizures. The BDNF levels correlated with epilepsy duration (σ = − 0.355; p = 0.040) and fractional anisotropy (FA) in the left temporal lobe, left thalamus, and right hippocampus. Using a regression model, BDNF level predicted verbal memory score. Further, design fluency scores were predicted by serum BDNF level via the interactions with left temporal FA.ConclusionsSerum BDNF levels reflected longer epilepsy duration, impaired white matter integrity, and poor cognitive function in patients with chronic TLE.     

Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center

ObjectiveThis study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom.MethodsThis study included 61 children aged between 2 and 18 years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom.ResultsOf the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p < 0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia.SignificanceResective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis indicate that a patient would have better results in terms of seizure freedom.     

A voxel-based morphometric study of cortical gray matter volume changes in Alzheimer’s disease with white matter hyperintensities

White matter hyperintensity (WMH) is commonly detected in patients with Alzheimer’s disease (AD), but its role in cortical impairment is unclear. This study investigated the effects of WMH on gray matter (GM) volume in patients with AD. We consecutively enrolled 84 patients with AD and 35 normal controls, who underwent brain MRI and were then classified according to WMH grade, based on a combination of deep white matter hyperintensity (DWMH) and periventricular white matter hyperintensity (PVWMH). The volume changes in GM were observed using voxel-based morphometry. It was found that global GM volume decreased with increasing WMH. Regional atrophies were in the dorsolateral frontal lobes, orbitofrontal gyri and insula (false discovery rate [FDR], p < 0.01). After controlling for PVWMH, DWMH affected cortical atrophy in the frontal lobe, insula and precuneus (FDR, p < 0.05), but PVWMH did not. Thus, WMH in AD is associated with GM volume reduction, especially in the frontal lobe, and DWMH is independently related to cortical atrophy.     

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.     

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.     

Is ‘burned-out hippocampus’ syndrome a distinct electro‐clinical variant of MTLE-HS syndrome?

AimTo study the clinical, electrophysiological and imaging characteristics of patients with unilateral mesial temporal lobe epilepsy (MTLE) with contralateral ictal onset on scalp EEG, viz. ‘burned-out hippocampus’ syndrome (MTLE-BHS).MethodsMTLE-BHS was defined as TLE with unilateral hippocampal sclerosis (HS) without any dual pathology on MRI and contralateral ictal onset on scalp EEG, unlike in classical hippocampal sclerosis (HS). Consecutive “MTLE-BHS” patients evaluated at our Centre for Comprehensive Epilepsy Care from January 2005 to July 2014 were studied. Twenty-five cases of classic MTLE-HS operated during the same period were also analyzed for comparison.ResultsSeventeen patients were diagnosed to have MTLE-BHS. Mean age of seizure onset was 9.5 ± 7.7 years and the mean duration of epilepsy was18.2 ± 7.3 years. Epigastric aura was more common in MTLE-HS and fear, secondary generalized seizures and temporal polar changes on MRI were more prevalent in the MTLE-BHS subgroup. In the latter group, five (29%) exhibited seizure semiology and 2 (12%) had interictal discharges discordant to the side of MTS. Eight (47%) patients in the MTLE-BHS sub-group had normal medial temporal volume on Scheltens scale. Eight patients among MTLE-BHS underwent surgery (4 following intracranial monitoring that localized to the side of HS) with Engel class I outcome at 1 year follow-up in 6 and Engel class II outcome in 2.ConclusionAttenuation of ipsilateral fast ictal rhythms on scalp EEG as well as neocortical changes are likely to be deterministic factors for MTLE-BHS as opposed to the severity of hippocampal atrophy. Considering good post-operative outcomes, intracranial monitoring for surgical selection is not mandatory in MTLE-BHS despite discordant semiology and ictal onset, in the presence of inter-ictal, functional imaging and neuropsychology data concordant to the side of HS.     

Alteration of functional connectivity within visuospatial working memory-related brain network in patients with right temporal lobe epilepsy: A resting-state fMRI study

PurposeThis study aimed to investigate the resting-state brain network related to visuospatial working memory (VSWM) in patients with right temporal lobe epilepsy (rTLE). The functional mechanism underlying the cognitive impairment in VSWM was also determined.MethodFifteen patients with rTLE and 16 healthy controls matched for age, gender, and handedness underwent a 6-min resting-state functional MRI session and a neuropsychological test using VSWM_Nback. The VSWM-related brain network at rest was extracted using multiple independent component analysis; the spatial distribution and the functional connectivity (FC) parameters of the cerebral network were compared between groups. Behavioral data were subsequently correlated with the mean Z-value in voxels showing significant FC difference during intergroup comparison.ResultsThe distribution of the VSWM-related resting-state network (RSN) in the group with rTLE was virtually consistent with that in the healthy controls. The distribution involved the dorsolateral prefrontal lobe and parietal lobe in the right hemisphere and the partial inferior parietal lobe and posterior lobe of the cerebellum in the left hemisphere (p < 0.05, AlphaSim corrected). Between-group differences suggest that the group with rTLE had a decreased FC within the right superior frontal lobe (BA8), right middle frontal lobe, and right ventromedial prefrontal lobe compared with the controls (p < 0.05, AlphaSim corrected). The regions of increased FC in rTLE were localized within the right superior frontal lobe (BA11), right superior parietal lobe, and left posterior lobe of the cerebellum (p < 0.05, AlphaSim corrected). Moreover, patients with rTLE performed worse than controls in the VSWM_Nback test, and there were negative correlations between ACCmeanRT (2-back) and the mean Z-value in the voxels showing decreased or increased FC in rTLE (p < 0.05).ConclusionThe results suggest that the alteration of the VSWM-related RSN might underpin the VSWM impairment in patients with rTLE and possibly implies a functional compensation by enlarging the FC within the ipsilateral cerebral network.     

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy

PurposeTo study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location.MethodsEight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction.ResultsThe distances between active electrode location and estimated ictal onset zone were 11 ± 4.3 or 9.1 ± 2.3 mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N = 6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3 mm from the subiculum (p < 0.05). The 2 non-responders patients were stimulated on contacts located >3 mm to the subiculum.ConclusionDecrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.     

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.     

Temporal lobe epilepsy: Decreased thalamic resting-state functional connectivity and their relationships with alertness performance

ObjectivesStudies have provided evidence regarding the pathology of the thalamus in patients with temporal lobe epilepsy (TLE). The thalamus, particularly the right thalamus, is one of the subcortical structures that are most uniformly accepted as being significantly involved in alertness. Moreover, alertness impairment in epilepsy has been reported. This study aimed to investigate alterations in thalamic resting-state functional connectivity (FC) and their relationships with alertness performance in patients with TLE; an issue that has not yet been addressed.MethodsA total of 15 patients with right TLE (rTLE) and 16 healthy controls were recruited for the present study. All of the participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and the attention network test (ANT). Whole-brain voxel-wise FC analyses were applied to extract the thalamic resting-state functional networks in the patients with rTLE and healthy controls, and the differences between the two groups were evaluated. Correlation analyses were employed to examine the relationships between alterations in thalamic FC and alertness performance in patients with rTLE.ResultsCompared to the healthy controls, the FC within and between the bilateral thalamus was decreased in the patients with rTLE. Moreover, in the patient group, the bilateral anterior cingulate cortex (ACC) and subcortical regions, including the bilateral brainstem, cerebellum, putamen, right caudate nucleus, and amygdala, exhibited decreased FC with the ipsilateral thalamus (p < 0.05, AlphaSim corrected, cluster size > 44) but not with the contralateral thalamus (p < 0.05, AlphaSim corrected, cluster size > 43). The intrinsic and phasic alertness performances of the patients were impaired (p = 0.001 and p < 0.001, respectively) but not correlated with decreased thalamic FC. Meanwhile, the alertness performance was not altered in right TLE but was negatively correlated with decreased thalamic FC with ACC (p < 0.05).ConclusionsOur findings highlight the functional importance of the thalamus in TLE pathology and suggest that damage to the thalamic resting-state functional networks, particularly ipsilateral to the epileptogenic focus, is present in patients with TLE.