Focal Temporal Lobe Epilepsy Research Articles

Medial septal GABAergic neurons reduce seizure duration upon optogenetic closed-loop stimulation.

Seizures can emerge from multiple or large foci in temporal lobe epilepsy, complicating focally targeted strategies such as surgical resection or the modulation of the activity of specific hippocampal neuronal populations through genetic or optogenetic techniques. Here, we evaluate a strategy in which optogenetic activation of medial septal GABAergic neurons, which provide extensive projections throughout the hippocampus, is used to control seizures. We utilized the chronic intrahippocampal kainate mouse model of temporal lobe epilepsy, which results in spontaneous seizures and as is often the case in human patients, presents with hippocampal sclerosis. Medial septal GABAergic neuron populations were immunohistochemically labelled and were not reduced in epileptic conditions. Genetic labelling with mRuby of medial septal GABAergic neuron synaptic puncta and imaging across the rostral to caudal extent of the hippocampus, also indicated an unchanged number of putative synapses in epilepsy. Furthermore, optogenetic stimulation of medial septal GABAergic neurons consistently modulated oscillations across multiple hippocampal locations in control and epileptic conditions. Finally, wireless optogenetic stimulation of medial septal GABAergic neurons, upon electrographic detection of spontaneous hippocampal seizures, resulted in reduced seizure durations. We propose medial septal GABAergic neurons as a novel target for optogenetic control of seizures in temporal lobe epilepsy.

Parameters of autonomic regulation in patients with focal frontal and temporal epilepsy

Aim. This study aimed to investigate the mechanisms of autonomic regulation and autonomic support in focal frontal and temporal lobe epilepsy.
 Materials and Methods. Thirty-six individuals were examined (19 men and 17 women; mean age 33.71.4 years) in the control group (without history of epileptic seizures) and 68 patients (32 men and 36 women, 34.11.5 years) with focal epilepsy (36 patients with frontal lobe epilepsy, of which 32 had temporal lobe epilepsy). Physiological parameters of heart rate variability and of skin sympathetic evoked potentials were evaluated.
 Results. Predomination of sympathetic influences in both groups of patients was found. According to the analysis of skin sympathetic evoked potentials, a high activity of the suprasegmental autonomic centers was determined in patients with epilepsy. Based on the results of the correlation analysis, the initial state in patients with temporal lobe epilepsy was characterized by greater intrasystemic tension that reflects the high level of physiological costs. The logit regression analysis model makes it possible to distribute patients with focal epilepsy into groups with different disease courses on the basis of the parameters of the autonomic support of the activity.
 Conclusion. In patients with focal epilepsy, predomination of sympathetic influences was observed, as well as greater activity of the suprasegmental centers of the autonomic regulation. Intrasystemic ratios of autonomic regulation parameters demonstrate an increase in the intrasystemic tension and a limitation of functional reserves in patients with temporal lobe epilepsy. A complex of parameters of autonomic support allows, based on the logit regression analysis, to distribute patients into groups with different courses of focal epilepsy.

Computer Assisted Planning for Curved Laser Interstitial Thermal Therapy.

The clinical feasibility and potential of curved LiTT trajectories through steerable needles has yet to be investigated. This is the focus of our work. We propose a GPU-accelerated computer-assisted planning (CAP) algorithm for steerable needle insertions that generates optimized curved 3D trajectories with maximal ablation of the amygdalohippocampal complex and minimal collateral damage to nearby structures, while accounting for a variable ablation diameter ( 5-15 mm). Simulated trajectories and ablations were performed on 5 patients with mesial temporal sclerosis (MTS), which were identified from a prospectively managed database. The algorithm generated obstacle-free paths with significantly greater target area ablation coverage and lower PHG ablation variance compared to straight line trajectories. The presented CAP algorithm returns increased ablation of the amygdalohippocampal complex, with lower patient risk scores compared to straight-line trajectories. This is the first clinical application of preoperative planning for steerable needle based LiTT. This study suggests that steerableneedles have the potential to improve LiTT procedure efficacy whilst improving the safety and should thus be investigated further.

Comparison of T2 relaxometry and PET CT in the evaluation of patients with mesial temporal lobe epilepsy using video EEG as the reference standard

PurposeOur study aimed to compare the sensitivity of T2 relaxometry and positron emission tomography – computed tomography (PET/CT) in patients with a history suggestive of mesial temporal lobe epilepsy using video electroencephalography (EEG) as the reference standard.Material and methodsIn our study, 35 patients with a history suggestive of mesial temporal lobe epilepsy were subjected to conventional magnetic resonance imaging (MRI), T2 relaxometry, and PET/CT. The results of each of the studies were compared with video EEG findings. Analyses were performed by using statistical software (SPSS version 20.0 for windows), and the sensitivity of conventional MRI, T2 relaxometry, and PET/CT were calculated.ResultsThe sensitivity of qualitative MRI (atrophy and T2 hyperintensity), quantitative MRI (T2 relaxometry), and PET/CT in lateralizing the seizure focus were 68.6% (n = 24), 85.7% (n = 30), and 88.6% (n = 31), respectively.ConclusionsThe sensitivity of MRI in lateralization and localization of seizure focus in temporal lobe epilepsy can be increased by adding the quantitative parameter (T2 relaxometry) with the conventional sequences. T2 Relaxometry is comparable to PET/CT for localization and lateralization of seizure focus and is a useful tool in the workup of TLE patients.

Dendritic pathology, spine loss and synaptic reorganization in human cortex from epilepsy patients.

Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmission and may be critically involved in the pathophysiology of epilepsy. Alterations in dendritic morphology and spine loss mainly in hippocampal neurons have been reported both in epilepsy animal models and in human brain tissues from patients with epilepsy. However, it is still unclear whether these dendritic abnormalities relate to the cause of epilepsy or are generated by seizure recurrence. We investigated fine neuronal structures at the level of dendritic and spine organization using Golgi impregnation, and analysed synaptic networks with immunohistochemical markers of glutamatergic (vGLUT1) and GABAergic (vGAT) axon terminals in human cerebral cortices derived from epilepsy surgery. Specimens were obtained from 28 patients with different neuropathologically defined aetiologies: type Ia and type II focal cortical dysplasia, cryptogenic (no lesion) and temporal lobe epilepsy with hippocampal sclerosis. Autoptic tissues were used for comparison. Three-dimensional reconstructions of Golgi-impregnated neurons revealed severe dendritic reshaping and spine alteration in the core of the type II focal cortical dysplasia. Dysmorphic neurons showed increased dendritic complexity, reduction of dendritic spines and occasional filopodia-like protrusions emerging from the soma. Surprisingly, the intermingled normal-looking pyramidal neurons also showed severe spine loss and simplified dendritic arborization. No changes were observed outside the dysplasia (perilesional tissue) or in neocortical postsurgical tissue obtained in the other patient groups. Immunoreactivities of vGLUT1 and vGAT showed synaptic reorganization in the core of type II dysplasia characterized by the presence of abnormal perisomatic baskets around dysmorphic neurons, in particular those with filopodia-like protrusions, and changes in vGLUT1/vGAT expression. Ultrastructural data in type II dysplasia highlighted the presence of altered neuropil engulfed by glial processes. Our data indicate that the fine morphological aspect of neurons and dendritic spines are normal in epileptogenic neocortex, with the exception of type II dysplastic lesions. The findings suggest that the mechanisms leading to this severe form of cortical malformation interfere with the normal dendritic arborization and synaptic network organization. The data argue against the concept that long-lasting epilepsy and seizure recurrence per se unavoidably produce a dendritic pathology.

New vision on the mental problems of Vincent van Gogh; results from a bottom-up approach using (semi-)structured diagnostic interviews

BackgroundOn July 29, 1890 at the age of 37 years, the Dutch painter Vincent van Gogh died from the consequences of a suicide attempt with a gun 2 days earlier. Since then many medical and psychological theories were suggested about what had happened to Van Gogh.AimTo present an overview of the history of the mental problems of Van Gogh and the most likely diagnoses.Method(Semi-)structured diagnostic interviews were applied to three art historians who are very familiar with Van Gogh from his correspondence and other sources as well as a neuropsychiatric examination to evaluate whether the symptoms might be explained by a medical condition.ResultsSeveral previously suggested diagnoses could be excluded as being highly unlikely, while other diagnoses could be classified as more of less likely.ConclusionMost likely Van Gogh suffered from comorbid illnesses. Since young adulthood, he likely developed a (probably bipolar) mood disorder in combination with (traits of) a borderline personality disorder as underlying vulnerability. This likely worsened through an alcohol use disorder combined with malnutrition, which then led, in combination with rising psychosocial tensions, to a crisis in which he cut off his ear. Thereafter, he likely developed two deliriums probably related to alcohol withdrawal, followed by a worsening with severe depressive episodes (of which at least one with psychotic features) from which he did not fully recover, finally leading to his suicide. As additional comorbidity, focal (temporal lobe) epilepsy cannot be excluded.

Epileptogenic zone localization using a new automatic quantitative analysis based on normal brain glucose metabolism database

Objectives To assess the clinical value of voxel-based automatic quantitative analysis using a normal brain glucose metabolism database in the preoperative localization of focal intractable temporal lobe epilepsy patients. Methods Patients with refractory temporal lobe epilepsy who underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging were retrospectively enrolled from January to June 2017. Visual analysis was performed by two nuclear medicine radiologists, and the automatic quantitative analysis was carried out using MIMneuro software based the age- and gender-stratified normal brain glucose metabolism database. Setting postoperative outcomes as reference, the consistency between visual analysis and automatic quantitative analysis was tested by Cohen’s kappa coefficient, and differences in localization of epileptic foci of the two methods were compared by Chi-square test. Results A total of 32 patients intractable temporal lobe epilepsy were included in this study. There was a moderate agreement between the automatic quantitative analysis based on MIMneuro software and visual analysis (kappa coefficient = 0.472, p = 0.002). In terms of the efficiency of focus localization, the voxel-based automatic quantitative analysis was higher than that of visual analysis (Chi-square value = 6.969, p = 0.008). Conclusions The voxel-based automatic quantitative analysis combined with normal brain glucose metabolism database had a certain clinical application value for detection temporal lobe epilepsy.

Mean apparent propagator-MRI: A new diffusion model which improves temporal lobe epilepsy lateralization

PurposeTo compare MRI volume measurements, FLAIR image intensity, Diffusion tensor imaging (DTI) and mean apparent propagator (MAP)-MRI measurements in hippocampus ipsilateral and contralateral to the epileptogenic focus for non-invasive lateralization of temporal lobe epilepsy (TLE) and also compare these DTI and MAP-MRI measurements to cognitive function. MethodA cohort of patients with unilateral TLE and aged-and gendered-matched controls were enrolled in this retrospective study. T1-weighted MPRAGE data for the volume, FLAIR image intensity, DTI and MAP-MRI parameters were performed for bilateral hippocampi of all subjects. The sensitivity, specificity, lateralization ratios and Cohen's d effect sizes of all MR measurements were calculated. Pearson correlation analysis was performed to compare DTI and MAP-MRI measurements to cognitive function. ResultsWe evaluated 23 patients and 17 controls. The MAP-MRI parameter ‘return to the plane probability’ (RTPP) had the strongest effect size (d = −1.678, lateralization ratio = 86.36 %) for differentiating hippocampus ipsilateral to the epileptogenic focus from contralateral hippocampus when compared to all other DTI/MAP-MRI parameters, signal intensity on FLAIR and hippocampal volumes. Mean diffusivity (MD), radial diffusivity (RD), mean square displacement (MSD) were each negatively correlated to clinical measures of delayed recall (r = −0.758; r = −0.772; r = −0.684, respectively). While return to the axis probability (RTAP) return to the origin probability (RTOP) and fractional anisotropy (FA) were positively correlated (r = 0.832; r = 0.813; r = 0.717, respectively) (all P < 0.05). ConclusionMAP-MRI measurements are promising radiologic biomarkers for the non-invasive lateralization of epileptogenic foci in TLE.

Comparison of psychiatric comorbidities and impact on quality of life in patients with epilepsy or psychogenic nonepileptic spells

ObjectivesPsychiatric comorbidity is common in people with epilepsy (PWE) and psychogenic nonepileptic spells (PNES). These comorbidities can be detrimental to quality of life (QOL) and are often underdiagnosed and undertreated. Some types of epilepsy, such as focal temporal lobe epilepsy (TLE), have been associated with higher rates of psychiatric comorbidity. This study examined the impact of psychiatric comorbidity on QOL in patients admitted to two level 4 epilepsy monitoring units (EMUs). MethodsIn this prospective observational study, 200 patients admitted to two level 4 EMUs completed standardized surveys including the Quality of Life in Epilepsy (QOLIE-31-P), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Beck Depression Inventory-II (BDI-II). Hierarchal multiple regression was performed to assess impact on QOL. ResultsOf the 200 participants, 113 had a diagnosis of epilepsy, 36 had a diagnosis of PNES, and 51 were excluded for nondiagnostic evaluation or dual diagnosis. Of those with epilepsy, 65 had TLE, 28 had focal extratemporal lobe epilepsy (ETLE), and 20 had nonfocal epilepsy. Patients with PNES had higher self-reported anxiety and depression levels (GAD-7: p = 0.04, PHQ-9: p < 0.01; BDI-II: p < 0.01) but similar QOL to PWE (p = 0.78). Using hierarchal multiple regression, symptoms of anxiety and depression were significant predictors of lower QOL in PWE but not in patients with PNES. There was no difference in QOL in those with ETLE and TLE. ConclusionsOur findings suggest that self-reported anxiety and depression symptoms are common in patients admitted to level 4 EMUs regardless of diagnosis and play an important role in predicting QOL in PWE. Our findings emphasize the importance of routinely screening all EMU patients for psychiatric comorbidity.

P31 Optimising trajectories in computer assisted planning for cranial laser interstitial thermal therapy: a machine learning approach

ObjectivesOptimal trajectory planning for cranial laser interstitial thermal therapy (cLITT) in drug resistant focal mesial temporal lobe epilepsy (MTLE).DesignA composite ablation score of ablated AHC minus ablated PHG volumes were calculated and normalised. Random forest and linear regression were implemented to predict composite ablation scores and determine the optimal entry and target point combinations to maximize this.SubjectsTen patients with hippocampal sclerosis were included.MethodsComputer Assisted Planning (CAP) cLITT trajectories were generated using entry regions that include the inferior occipital gyri (IOG), middle occipital gyri (MOG), inferior temporal gyri (ITG) and middle temporal gyri (MTG). Target points were varied by sequential erosions and transformations of the centroid of the amygdala. In total 760 trajectory combinations were generated per patient and ablation volumes were calculated based on a conservative 15 mm maximum ablation diameter.ResultsLinear regression was superior to random forest predictions. Linear regression indicated that maximal composite ablation scores were associated with entry points that clustered around the junction of the IOG, MOG and MTG. The optimal target point was a translation of the centroid of the amygdala anteriorly and medially.ConclusionsMachine learning techniques accurately predict composite ablation scores with linear regression outperforming the random forest approach. Optimal CAP entry points for cLITT maximize ablation of the AHC and spare the PHG.

F10. Co-localization of ictal and interictal activity using high density EEG data

Despite major advances in using high density EEG (hdEEG) and electrical source imaging (ESI) for analysis of interictal activity, research demonstrating its utility in examining ictal activity is still lacking. This may be a result of technical challenges associated with capturing epileptic seizures on scalp hdEEG recordings (physical constraints, such as high number of sensors, lack of standardization in review, comfort, etc.). Furthermore, the value of using interictal discharges as a valid estimate of seizure onset zone (SOZ) still remains disputable. The aim of this study is to use electrical source imaging (ESI) to evaluate the co-localization of ictal and interictal activity through the use of high density scalp EEG. A retrospective analysis was performed on 5 patients with intractable focal temporal and extratemporal lobe epilepsy. EEG scalp recordings were obtained using high density 256 Geodesic Sensory Net (Geodesic Sensor Net, Electrical Geodesic Inc.). ESI was performed using two different commercially available ESI systems, Curry 7.0 (Compumedics) and MIPEGI (Electrical Geodesic Inc.). Sensor locations were determined using the Geodesic Photogrammetry System (GPS) and Geosource 3 (Electrical Geodesic Inc), Realistic geometric individualized head models were constructed from patient specific MRIs using the boundary element model and the finite difference model. Source reconstruction was based on distributed source models and dipole models. The concordance of irritative and ictal onset zones was estimated by the distance between maximal ictal and interictal source activity. ESI identified the seizure onset and irritative zones in all 5 patients. There was good concordance between the estimated seizure onset zone and irritative zone on the sub-lobar level. Similar results were obtained through the use of the boundary element and finite difference models. The results provide insight into whether interictal discharges provide accurate estimate of SOZ. Furthermore, these results assess similarity of source reconstruction obtained through two different types of individual head models that are commercially available.

Review: Animal models of acquired epilepsy: insights into mechanisms of human epileptogenesis.

In many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, that is, segmental neuronal cell loss and concomitant astrogliosis. Many TLE patients report on transient brain insults early in life, which is followed by a 'latency' period lacking seizure activity of months or even years before chronic recurrent seizures start. The plethora of structural and cellular mechanisms that convert the hippocampal formation to become chronically hyperexcitable after a transient insult to the brain are summarized under the term epileptogenesis. In contrast to the obstacles arising for experimental studies of epileptogenesis aspects in human surgical hippocampal tissue, recent animal model approaches allow insights into mechanisms of epileptogenesis. Relevant models of transient brain insults in this context comprise several distinct types of lesions including excitoxic status epilepticus (SE), electrical seizure induction, traumatic brain injury, induction of inflammatory processes by hyperthermia and viral inflammation and others. In pathogenetic terms, aberrant transcriptional and epigenetic reprogramming, acquired channel- and synaptopathies, neuronal network and blood-brain barrier dysfunction as well as innate and adaptive immunity-mediated damage play major roles. In subsequent steps, respective animal models have been used in order to test whether this dynamic process can be either retarded or even abolished by interfering with epileptogenic mechanisms. Well-controlled subsequent analyses of epileptogenic cascades characterized in animal models using carefully stratified human hippocampal biopsies to exploit the unique opportunities given by these rare and precious brain tissue samples aim to translate into novel antiepileptogenic approaches. Respective preclinical tests can open entirely new perspectives for tailor-made treatments in patients with the potential to avoid the emergence of chronic focal seizure events.

ATPase N-ethylmaleimide-sensitive Fusion Protein: A Novel Key Player for Causing Spontaneous Network Excitation in Human Temporal Lobe Epilepsy

The molecular basis for onset, maintenance and propagation of excitation along neuronal networks in epilepsy is still poorly understood. Besides different neurotransmitter receptors that control signal transfer at the synapse, one key regulator involved in all of these processes is the ATPase N-ethylmaleimide-sensitive fusion protein (NSF). Therefore, we analyzed receptor subunits and NSF levels in tissues from the medial temporal gyrus (MTG) of patients with pharmaco-resistant focal temporal lobe epilepsy resected during epilepsy surgery and autopsy controls. The resected tissues were further characterized by field potential recordings into tissues with and without spontaneous sharp wave activity. We detected increased levels of NSF, NMDA 1.1, 2A and GABAAγ2 receptor subunits associated with spontaneous sharp wave spiking activity. We further identified correlations between NSF, AMPA receptor subunit, metabotropic glutamate receptor and adenosine 1 receptor levels in the spontaneous sharp wave spiking tissues. Our findings suggest that NSF plays a key role in controlling spontaneous network excitation in epilepsy by two mechanisms of action: (1) directly via controlling transmitter release at the presynaptic side, and (2) indirectly via altering the function of possible receptor crosstalk and directing/integrating specific receptor compounds through/into the postsynaptic membrane.

Manipulation of Epileptiform Electrocorticograms (ECoGs) and Sleep in Rats and Mice by Acupuncture.

Ancient Chinese literature has documented that acupuncture possesses efficient therapeutic effects on epilepsy and insomnia. There is, however, little research to reveal the possible mechanisms behind these effects. To investigate the effect of acupuncture on epilepsy and sleep, several issues need to be addressed. The first is to identify the acupoints, which correspond between humans, rats, and mice. Furthermore, the depth of insertion of the acupuncture needle, the degree of needle twist in manual needle acupuncture, and the stimulation parameters for electroacupuncture (EA) need to be determined. To evaluate the effects of acupuncture on epilepsy and sleep, a feasible model of epilepsy in rodents is required. We administer pilocarpine into the left central nucleus of the amygdala (CeA) to simulate focal temporal lobe epilepsy (TLE) in rats. Intraperitoneal (IP) injection of pilocarpine induces generalized epilepsy and status epilepticus (SE) in rats. Five IP injections of pentylenetetrazol (PTZ) with a one-day interval between each injection successfully induces spontaneous generalized epilepsy in mice. Recordings of electrocorticograms (ECoGs), electromyograms (EMGs), brain temperature, and locomotor activity are used for sleep analysis in rats, while ECoGs, EMGs, and locomotor activity are employed for sleep analysis in mice. ECoG electrodes are implanted into the frontal, parietal, and contralateral occipital cortices, and a thermistor is implanted above the cerebral cortex by stereotactic surgery. EMG electrodes are implanted into the neck muscles, and an infrared detector determines locomotor activity. The criteria for categorizing vigilance stages, including wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep are based on information from ECoGs, EMGs, brain temperature, and locomotor activity. Detailed classification criteria are stated in the text.

Brain Infiltration of Immune Cells in CASPR2-Antibody Associated Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Antibodies directed against neuronal surface antigens have recently been identified in patients with focal temporal lobe epilepsy (TLE) of unknown cause and mesial TLE with hippocampal sclerosis (MTLE-HS), thereby emphasizing the role of autoimmunity in TLE. Antibodies to contactin-associated protein-like 2 (CASPR2) are prevalent in MTLE-HS patients. We aimed to find out whether anti-neuronal autoimmunity might be involved in CASPR2 antibody-related MTLE-HS. Surgically resected medial temporal lobe specimens of seropositive and seronegative MTLE-HS patients were examined with hematoxylin and eosin and immunohistochemical staining using specific immune cell markers. Two of 5 CASPR2 antibody-positive MTLE-HS patients showed polymorphonuclear and mononuclear cells infiltrating the subarachnoidal region. One of these patients also showed mononuclear cell infiltration in the parenchyma of the temporal lobe cortex. Subarachnoidal and parenchymal infiltrates contained CD3+, CD8+, and CD68+ cells. None of the 13 seronegative MTLE-HS patients displayed cellular infiltrates in their brain samples, and all MTLE-HS patients showed marked neuronal cell loss but no immune cell infiltration in their hippocampi. Our results show that CASPR2 antibody-associated MTLE-HS can present with central nervous system inflammation; thus, this subtype of MTLE-HS might have an autoimmune origin.

Investigation of hippocampal substructures in focal temporal lobe epilepsy with and without hippocampal sclerosis at 7T.

To provide a more detailed investigation of hippocampal subfields using 7T magnetic resonance imaging (MRI) for the identification of hippocampal sclerosis in temporal lobe epilepsy (TLE). Patients (n = 13) with drug-resistant TLE previously identified by conventional imaging as having hippocampal sclerosis (HS) or not (nine without HS, four HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( R2*) were studied between the two groups. In addition, qualitative assessment at 7T and clinical outcomes were correlated with measured subfield changes. Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 (P = 0.001) and CA4+DG (P < 0.001). Volumetry also uncovered subfield atrophy in 33% of patients without HS, which had not been detected using conventional imaging. R2* was significantly lower in the CA4+DG subfields (P = 0.001) and the whole hippocampus (P = 0.029) of HS patients compared to controls but not significantly lower than the group without HS (P = 0.077, P = 0.109). No correlation was found between quantitative volumetry and qualitative assessment as well as surgical outcomes (Sub, P = 0.495, P = 0.567, P = 0.528; CA1, P = 0.104 ± 0.171, P = 0.273, P = 0.554; CA2+CA3, P = 0.517, P = 0.952, P = 0.130 ± 0.256; CA4+DG, P = 0.052 ± 0.173, P = 0.212, P = 0.124 ± 0.204; WholeHipp, P = 0.187, P = 0.132 ± 0.197, P = 0.628). These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T is capable of identifying characteristic patterns of hippocampal atrophy in HS patients; however, difficulty remains in using imaging to identify hippocampal pathologies in cases without HS. 2 J. MAGN. RESON. IMAGING 2017;45:1359-1370.

Increased MRI volumetric correlation contralateral to seizure focus in temporal lobe epilepsy

Quantification of volumetric correlation may be sensitive to disease alterations undetected by standard voxel based morphometry (VBM) such as subtle, synchronous alterations in regional volumes, and may provide complementary evidence of the structural impact of temporal lobe epilepsy (TLE) on the brain. The purpose of this study was to quantify differences of regional volumetric correlation in right (RTLE) and left (LTLE) TLE patients compared to healthy controls. A T1 weighted 3T MRI was acquired (1mm3) in 44 drug resistant unilateral TLE patients (n=26 RTLE, n=18 LTLE) and 44 individually age and gender matched healthy controls. Images were processed using a standard VBM framework and volumetric correlation was calculated across subjects in 90 regions and compared between patients and controls. Results were summarized across hemispheres and region groups. There was increased correlation involving the contralateral homologues of the seizure foci/network in the limbic, subcortical and temporal regions in both RTLE and LTLE. Outside these regions, results implied widespread correlated alterations across several contralateral lobes in LTLE, with more focal changes in RTLE. These findings complement previous volumetric studies in TLE describing more ipsilateral atrophy, by revealing subtle coordinated volumetric changes to identify a more widespread effect of TLE across the brain.

P.027 Investigation of hippocampal sub-structures in HS and non-HS focal temporal lobe epilepsy at 7T

Background: The clinical identification of hippocampal sclerosis (HS) is important in predicting surgical outcomes in patients with temporal lobe epilepsy (TLE). In cases where gross hippocampal sclerosis is not identifiable clinically, a more detailed analysis of hippocampal subfields using ultra-high-field magnetic resonance imaging (MRI) may reveal areas of abnormality, which was the focus of our study. Methods: Patients (N=13) with drug-resistant TLE (9 no-HS, 4 HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes were studied between the two groups. In addition, radiological patient assessment at 7T was correlated with measured subfield changes. Results: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield losses in CA1 and CA4DG. Volumetry also uncovered subfield volume losses in 33% of no-HS patients, which had not been detected conventionally. Furthermore, 89% of no-HS patients showed abnormality (internal architecture or size) at 7T, identified by radiologists blinded to the patient’s initial classification. Conclusions: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T may be superior to conventional visual inspection by a neuroradiologist in the identification of hippocampal pathologies in TLE.

Utility of Home-Made Videos in an Adult Epilepsy Clinic

Introduction: According to the ILAE, the definition of epilepsy requires the occurrence at least one epileptic seizure. Up to 20% of patients diagnosed of epilepsy are not actually epileptic. An accurate diagnosis is necessary for a satisfactory management of patients with Epilepsy. New broad access image technologies allow patients and families to record homemade videos helping neurologists in diagnosis. Method: During a two-year period in an epilepsy clinic, consecutive patients were encouraged to record their events with any available device. Instructions for good quality videos were given. Three neurologists/epileptologists watched the videos in clinical session, rated the quality of the recordings following some parameters and made a clinical diagnosis. In a second phase, previous diagnosis was revised. Results: 314 consecutive patients (relatives) were encouraged to record events. 52% male. Average age: 46 years. 267 patients had video recording devices available (87%) (Photo camera: 100%, cell-phone: 100%, webcam: 10%, video camera: 30%). From this group, 135 (50%) felt unable to record events. Reasons given: Low seizure frequency: 60%, seizures short duration: 80%. 50 events from 22 patients recorded. Mean age: 35 years. Seizure frequency three months prior to video deposit was 3, 5 seizures/patient/month. Previous epileptic syndrome diagnosed (based on description/neuroimaging/EEG): 15 focal temporal lobe epilepsy, 4 focal frontal probably symptomatic epilepsy, 3 epileptic encephalopathy. Type of seizures recorded: Focal motor with typical automatisms: 14 seizures/11 patients. Focal motor with hyperkinetic automatisms: 9 seizures/2 patients. Asymmetrical tonic motor seizures: 4 seizures/1 patient. Focal clonic seizure: 5 seizures/1 patients. Atypical absence seizure: 6 seizures/3 patients. Non-epileptic Seizure (NES): 13 seizures/3 patients. Postural tremor: 1 patient. There was agreement in diagnosis but in one. 18 patients were confirmed in their Diagnosis: Epilepsy misdiagnosis: 4. Three NES and one undetermined tremor. Conclusion: Homemade videos may be of diagnostic value in epilepsy management. Training in performing good-quality videos is necessary. Webcam long term recordings should be recommended as the best recording option.

PDGFRβ+ cells in human and experimental neuro-vascular dysplasia and seizures

Introduction: Neuro-vascular rearrangement occurs in brain disorders, including epilepsy. Platelet-derived growth factor receptor beta (PDGFRβ) is used as a marker of perivascular pericytes. Whether PDGFRβ+ cell reorganization occurs in regions of neuro-vascular dysplasia associated with seizures is unknown. Methods: We used brain specimens derived from epileptic subjects affected by intractable seizures associated with focal cortical dysplasia (FCD) or temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Tissues from cryptogenic epilepsy, non-sclerotic hippocampi or peritumoral were used for comparison. An in vivo rat model of neuro-vascular dysplasia was obtained by pre-natal exposure to methyl-axozy methanoic acid (MAM). Status epilepticus (SE) was induced in adult MAM rats by intraperitoneal pilocarpine. MAM tissues were also used to establish organotypic hippocampal cultures (OHC) to further assess pericytes positioning at the dysplastic microvasculature. PDGFRβ and its colocalization with RECA-1 or CD34 were used to segregate perivascular pericytes. PDGFRβ and NG2 or IBA1 colocalization were performed. Rat cortices and hippocampi were used for PDGFRβ western blot analysis. Results: Human FCD displayed the highest perivascular PDGFRβ immunoreactivity, indicating pericytes, and presence of ramified PDGFRβ+ cells in the parenchyma and proximal to microvessels. Tissues deriving from human cryptogenic epilepsy displayed a similar pattern of immunoreactivity, although to a lesser extent compared to FCD. In TLE-HS, CD34 vascular proliferation was paralleled by increased perivascular PDGFRβ+ pericytes, as compared to non-HS. Parenchymal PDGFRβ immunoreactivity co-localized with NG2 but was distinct from IBA1+ microglia. In MAM rats, we found pericyte-vascular changes in regions characterized by neuronal heterotopias. PDGFRβ immunoreactivity was differentially distributed in the heterotopic and adjacent normal CA1 region. The use of MAM OHC revealed microvascular-pericyte dysplasia at the capillary tree lining the dentate gyrus (DG) molecular layer as compared to control OHC. Severe SE induced PDGFRβ+ immunoreactivity mostly in the CA1 region of MAM rats. Conclusion: Our descriptive study points to microvascular-pericyte changes in the epileptic pathology. The possible link between PDGFRβ+ cells, neuro-vascular dysplasia and remodeling during seizures is discussed.