MRI Signs Of Hippocampal Sclerosis Research Articles

Longitudinal analysis of interictal electroencephalograms in patients with temporal lobe epilepsy with hippocampal sclerosis

BackgroundWhile studies have shown the progression of atrophy in temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS), little is known about the long-term dynamics of interictal epileptiform discharges (IEDs). ObjectivesTo investigate long-term IEDs distribution in routine EEGs. MethodsWe evaluated 314 patients with TLE and MRI signs of HS (TLE-HS). Six had bilateral, 163 had left, and 145 had right HS. We analyzed 3655 routine EEGs (average 11.6 EEGs/patient). The EEGs were classified into four groups: (i) ipsilateral-IEDs (n = 1485), EEGs with only IEDs ipsilateral to the HS; (ii) bilateral-IEDs (n = 390); (iii) contralateral-IEDs (n = 186); and (iv) normal-EEGs (n = 1594). The duration of epilepsy at the time of the EEG (average 27.9 years) was divided into four groups: (a) <8 years (n = 140), (b) 9–17 years (n = 505), (c) 18–29 years (n = 1165), and (d) >30 years (n = 1845). We performed ANOVA with Tukey’s pairwise comparisons and linear regression analysis between the duration of epilepsy and the EEG groups. ResultsThe ANOVA showed a difference in the distribution of IEDs over time (p < 0.0001). While there were no significant changes in the relative numbers of bilateral and contralateral-IEDs combined, there was a significant increase in ipsilateral-IEDs (p < 0.0001) and a decrease in normal-EEGs (p < 0.0001) over time. The linear regression analysis confirmed that the proportion of ipsilateral-IEDs (p < 0.0001), and to a lesser extent, bilateral-IEDs (p = 0.0002), increased over time, while contralateral-IEDs were unchanged (p = 0.923). ConclusionsContrary to our expectations, contralateral-IEDs remained stable over time, whereas normal-EEGs decreased and ipsilateral-IEDs increased. Contralateral-IEDs may reflect early abnormalities and not epilepsy progression.

Impaired processing of response conflicts in mesial temporal lobe epilepsy.

Increasing evidence from neuroimaging studies points towards a hippocampal role in resolving approach-avoidance goal conflicts. Furthermore, previous neuroimaging findings suggest that the hippocampus (HC) contributes to successful conflict resolution as it is measured, for example, in a Stroop paradigm. However, it is still an open question whether the hippocampus is indeed causally relevant for resolving cognitive conflicts. Here, we investigated whether conflict resolution performance is affected by hippocampal pathology. N=30 patients with mesial temporal lobe epilepsy (MTLE), almost exclusively showing MRI signs of hippocampal sclerosis, and an equal number of age-matched healthy controls performed an auditory Stroop paradigm. Participants listened to the words 'high' and 'low', spoken in either a high or a low pitch. Subjects' response time and accuracy to the phonetic information in the presence of incongruent (conflict trials) or congruent (non-conflict trials) semantic information were assessed. In addition, patients' regional grey matter (GM) brain volumes were analysed. We observed an increased effect of conflict on accuracy in patients with MTLE compared to healthy controls. This effect was negatively correlated with right HC volume. The results suggest that the impairment in the resolution of a response conflict is related to hippocampal structural integrity and thus add further support to the notion that the HC is not only involved but even causally relevant for successful cognitive conflict processing.

MicroRNA hsa-miR-134 is a circulating biomarker for mesial temporal lobe epilepsy.

Epilepsy is misdiagnosed in up to 25% of patients, leading to serious and long-lasting consequences. Recently, circulating microRNAs have emerged as potential biomarkers in a number of clinical scenarios. The purpose of this study was to identify and to validate circulating microRNAs that could be used as biomarkers in the diagnosis of epilepsy. Quantitative real-time PCR was used to measure plasma levels of three candidate microRNAs in two phases of study: an initial discovery phase with 14 patients with mesial temporal lobe epilepsy (MTLE), 13 with focal cortical dysplasia (FCD) and 16 controls; and a validation cohort constituted of an independent cohort of 65 patients with MTLE and 83 controls. We found hsa-miR-134 downregulated in patients with MTLE (p = 0.018) but not in patients with FCD, when compared to controls. Furthermore, hsa-miR-134 expression could be used to discriminate MTLE patients with an area under the curve (AUC) of 0.75. To further assess the robustness of hsa-miR-134 as a biomarker for MTLE, we studied an independent cohort of 65 patients with MTLE, 27 of whom MTLE patients were responsive to pharmacotherapy, and 38 patients were pharmacoresistant and 83 controls. We confirmed that hsa-miR-134 was significantly downregulated in the plasma of patients with MTLE when compared with controls (p < 0.001). In addition, hsa-miR-134 identified patients with MTLE regardless of their response to pharmacotherapy or the presence of MRI signs of hippocampal sclerosis. We revealed that decreased expression of hsa-miR-134 could be a potential non-invasive biomarker to support the diagnosis of patients with MTLE.

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.

Longitudinal analysis of hippocampal T2 relaxometry in FMTLE

PurposeTo investigate the degree of T2 relaxometry changes over time in groups of patients with familial mesial temporal lobe epilepsy (FMTLE) and asymptomatic relatives. MethodsWe conducted both cross-sectional and longitudinal analyses of T2 relaxometry with Aftervoxel, an in-house software for medical image visualization. The cross-sectional study included 35 subjects (26 with FMTLE and 9 asymptomatic relatives) and 40 controls; the longitudinal study was composed of 30 subjects (21 with FMTLE and 9 asymptomatic relatives; the mean time interval of MRIs was 4.4±1.5years) and 16 controls. To increase the size of our groups of patients and relatives, we combined data acquired in 2 scanners (2T and 3T) and obtained z-scores using their respective controls. General linear model on SPSS21® was used for statistical analysis. ResultsIn the cross-sectional analysis, elevated T2 relaxometry was identified for subjects with seizures and intermediate values for asymptomatic relatives compared to controls. Subjects with MRI signs of hippocampal sclerosis presented elevated T2 relaxometry in the ipsilateral hippocampus, while patients and asymptomatic relatives with normal MRI presented elevated T2 values in the right hippocampus. The longitudinal analysis revealed a significant increase in T2 relaxometry for the ipsilateral hippocampus exclusively in patients with seizures. ConclusionsThe longitudinal increase of T2 signal in patients with seizures suggests the existence of an interaction between ongoing seizures and the underlying pathology, causing progressive damage to the hippocampus. The identification of elevated T2 relaxometry in asymptomatic relatives and in patients with normal MRI suggests that genetic factors may be involved in the development of some mild hippocampal abnormalities in FMTLE.

Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

ObjectivePatients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS).MethodsWe evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures.ResultsPatients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions.ConclusionAlthough a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process.

Amygdala enlargement occurs in patients with mesial temporal lobe epilepsy and hippocampal sclerosis with early epilepsy onset

Mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) is considered an electroclinical syndrome, and there is a debate whether it is a unique disease or an entity with distinct subtypes. Together with other mesial temporal structures, the amygdala is important in the epileptogenic network of patients with MTLE with HS. During automatic volumetric analysis of mesial structures in a group of 102 patients with MTLE with MRI signs of HS, we observed significant amygdala enlargement in 14 (14%) individuals compared to a group of 79 healthy subjects. The increased amygdala volume was contralateral to the epileptogenic zone and MRI signs of HS in 93% of these patients. Patients with MTLE with HS and enlarged amygdala had significantly earlier epilepsy onset than those without an increase of amygdala volumes. Mesial temporal lobe epilepsy with HS and enlarged amygdala may be a part of the spectrum of this condition.

Amygdala Enlargement in Patients with Mesial Temporal Lobe Epilepsy without Hippocampal Sclerosis

Purpose: Patients with mesial temporal lobe epilepsy (MTLE) without MRI abnormalities (MTLE-NL) represent a challenge for definition of underlying pathology and for presurgical evaluation. In a recent study we observed significant amygdala enlargement (AE) in 14% of MTLE patients with MRI signs of hippocampal sclerosis. Areas of gray matter volume (GMV) increase could represent structural abnormalities related to the epileptogenic zone or part of a developmental abnormality. Our objective was to look for undetected areas of increased GMV in MTLE-NL using post processing MRI techniques to better understand the pathophysiology of this condition.Methods: We evaluated 66 patients with MTLE-NL on visual analysis and 82 controls. Voxel-based morphometry (VBM) group analysis was performed with VBM8/SPM8 looking for areas of increased GMV. We then performed automatic amygdala volumetry using FreeSurfer software and T2 relaxometry to confirm VBM findings.Results: Voxel-based morphometry group-analysis demonstrated increased amygdala volume in the MTLE-NL group compared to controls. Individual volumetric analysis confirmed AE in eight (12%) patients. Overall, from all patients with AE and defined epileptic focus, four (57%) had the predominant increased volume ipsilateral to the epileptic focus. These results were cross-validated by a secondary VBM analysis including subgroups of patients according to the volumetric data. T2 relaxometry demonstrated no amygdala hyperintense signal in any individual with significant AE. There were no clinical differences between patients with and without AE.Discussion: This exploratory study demonstrates the occurrence of AE in 12% of patients with MTLE-NL. This finding supports the hypothesis that there might be a subgroup of patients with MTLE-NL in which the enlarged amygdala could be related to the epileptogenic process. Further studies are necessary but this finding could be of great importance in the understanding of MTLE-NL.

MRI signs of hippocampal sclerosis seen in healthy volunteers

Mesial temporal lobe epilepsy (MTLE) is the most frequent partial epilepsy among adults and is highly associated with hippocampal sclerosis (HS).1 Other temporal and extratemporal regions are known to be affected in patients with MTLE, mainly those with anatomic and functional connections to the hippocampus.2,3 MRI signs of HS, both hippocampal atrophy and hyperintense T2-weighted or fluid-attenuated inversion recovery (FLAIR) signal, may be found in patients with MTLE with good seizure control with antiepileptic drug (AED) treatment.4 By contrast, there are some patients with refractory MTLE and clearly localized EEG abnormalities in whom MRI is normal and HS is diagnosed on postoperative histopathology.2 This seemingly paradoxical relationship between the presence and intensity of MRI signs of HS and the presence and frequency of seizures is not yet fully understood. It is intuitive to assume that MTLE, HS, and response to AED therapy depend on a complex mix of multifactorial underlying conditions. Understanding these biologic factors is crucial for better care of individuals with MTLE. It is equally important to know whether some of …

Avoid falling into the depths of the insular trap

ABSTRACT Recent data have demonstrated that insular seizures can mimic those encountered in temporal lobe epilepsy (TLE), as well as nocturnal hypermotor attacks suggestive of nocturnal frontal lobe epilepsy (NFLE). To illustrate some of the issues raised by these observations, we report our first two patients with suspected TLE and NFLE, respectively, in whom we originally demonstrated an insular ictal onset zone. Patient 1 suffered from daytime seizures characterised by a rising and distressing epigastric sensation rapidly followed by oro‐alimentary automatisms, associated with right temporal scalp‐EEG ictal discharge. Neuroimaging showed consistent right temporal abnormalities, including MRI signs of hippocampal sclerosis, anterior and mesial glucose hypometabolism, and mesial decrease of benzodiazepine receptors. Intracerebral EEG investigation was primarily performed because of several ictal signs and symptoms suggesting a rapid involvement of the perisylvian region, and showed that the patient suffered two types of seizure, one of which arose from the mesial temporal structures, the other was sleep‐related and originated in the posterior‐inferior portion of the insula. Anterior temporal lobectomy failed to control this second type of seizure. Patient 2 suffered from brief, nocturnal, hypermotor seizures characterised by an indefinable aura followed by agitation, body rolling, scream and pelvic thrust. Interictal and ictal scalp‐EEG failed to detect epileptiform discharges, whereas neuroimaging showed left mesial frontal, glucose hypometabolism and decreased benzodiazepine receptors associated with a left fronto‐basal arachnoidal cyst. Invasive EEG monitoring was performed with the aim of identifying an orbital or mesial frontal ictal onset, but eventually demonstrated that the seizure originated in the anterior‐superior portion of the left insula. The patient did not undergo surgery and died of SUDEP two years later. We discuss the heterogeneity of insular seizure semiology according to functional anatomy, the clinical signs and symptoms that might suggest an insular ictal onset, the indications and types of invasive EEG monitoring that are needed to identify an insular epileptogenic zone definitively, as well as potential surgical treatment.

Clobazam as Add-on Therapy for Temporal Lobe Epilepsy and Hippocampal Sclerosis

Clobazam is a benzodiazepine with known antiepileptic action; however, it is not considered first line therapy in the treatment of epilepsy. The objective of this study was to evaluate the efficacy of clobazam as add-on therapy in adults with temporal lobe epilepsy associated with MRI evidence of hippocampal sclerosis (HS). This is a retrospective study, conducted at our epilepsy clinic which evaluated clobazam as add-on therapy in patients with temporal lobe epilepsy and MRI signs of HS. Clobazam was prescribed based on the minimum effective dose up to the maximum tolerated dose. Seventy-eight patients met the inclusion criteria (51 women), ages ranging from 16 to 76 years old (mean=42.2). Dosage of clobazam ranged from 5 to 60 mg/day (mean=22.6 mg/day). Clobazam was used from one month to eight years (mean=29 months). Sixteen (20.5%) patients were seizure-free, 20 (25.5%) had more than 75% improvement in seizure control, eight (10%) had more than 50% and 20 (26%) were non responders to clobazam. In 14 (18%) we could not determine seizure frequency during follow-up. The improvement in seizure control lasted for more than one year in 30 (68%) patients. Our data suggest that clobazam should be considered as add-on therapy in the treatment of patients with temporal lobe epilepsy associated with MRI signs of HS.

Temporal pole MRI abnormalities in temporal lobe epilepsy

ABSTRACT Magnetic resonance imaging (MRI) demonstrates an abnormal aspect of the temporo‐polar region in 1/3 to 2/3 of patients suffering from cryptogenic temporal lobe epilepsy. This abnormal aspect is described as a white matter increased T2 signal, resulting in a loss of gray‐white matter demarcation, often associated with atrophy, as recently confirmed by quantitative volumetric measurements. These temporo‐polar MRI findings appear to correctly lateralize the epileptogenic temporal lobe with a very high specificity, and have never been reported in extra‐temporal lobe epilepsy nor in control subjects. They are usually associated with MRI signs of hippocampal sclerosis, but the two conditions seem to be partly distinct from a pathophysiological point of view. Pathological correlates of temporo‐polar white matter increased T2 signal are controversial, but the role of an abnormal myelin seems more likely than that of ectopic neurons. A myelin dysfunction would also be consistent with the correlation observed between lateral temporal hypometabolism and temporo‐polar MRI abnormalities. Whether or not these MRI findings are associated with a better seizure outcome following temporal lobectomy remains a debated issue.