Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy.

OBJECTIVE: To investigate the pattern and severity of hippocampal subfield volume loss in patients with left and right mesial temporal lobe epilepsy (mTLE) using quantitative MRI volumetric analysis. METHODS: A total of 21 left and 14 right mTLE subjects, as well as 15 healthy controls, were enrolled in this cross-sectional study. A publically available magnetic resonance imaging (MRI) brain volumetry system (volBrain) was used for volumetric analysis of hippocampal subfields. The T1-weighted images were processed with a HIPS pipeline. RESULTS: A distinct pattern of hippocampal subfield atrophy was found between left and right mTLE patients when compared with controls. Patients with left mTLE exhibited ipsilateral hippocampal atrophy and segmental volume depletion of the Cornu Ammonis (CA) 2/CA3, CA4/dentate gyrus (DG), and strata radiatum-lacunosum-moleculare (SR-SL-SM). Those with right mTLE exhibited similar ipsilateral hippocampal atrophy but with additional segmental CA1 volume depletion. More extensive bilateral subfield volume loss was apparent with right mTLE patients. CONCLUSION: We demonstrate that left and right mTLE patients show a dissimilar pattern of hippocampal subfield atrophy, suggesting the pathophysiology of epileptogenesis in left and right mTLE to be different.

A Combination of Particle Swarm Optimization and Minkowski Weighted K-Means Clustering: Application in Lateralization of Temporal Lobe Epilepsy.

K-Means is one of the most popular clustering algorithms that partitions observations into nonoverlapping subgroups based on a predefined similarity metric. Its drawbacks include a sensitivity to noisy features and a dependency of its resulting clusters upon the initial selection of cluster centroids resulting in the algorithm converging to local optima. Minkowski weighted K-Means (MWK-Means) addresses the issue of sensitivity to noisy features, but is sensitive to the initialization of clusters, and so the algorithm may similarly converge to local optima. Particle Swarm Optimization (PSO) uses a globalized search method to solve this issue. We present a hybrid Particle Swarm Optimization (PSO) + MWK-Means clustering algorithm to address all the above problems in a single framework, while maintaining benefits of PSO and MWK Means methods. This study investigated the utility of this approach in lateralizing the epileptogenic hemisphere for temporal lobe epilepsy (TLE) cases using magnetoencephalography (MEG) coherence source imaging (CSI) and diffusion tensor imaging (DTI). Using MEG-CSI, we analyzed preoperative resting state MEG data from 17 adults TLE patients with Engel class I outcomes to determine coherence at 54 anatomical sites and compared the results with 17 age- and gender-matched controls. Fiber-tracking was performed through the same anatomical sites using DTI data. Indices of both MEG coherence and DTI nodal degree were calculated. A PSO + MWK-Means clustering algorithm was applied to identify the side of temporal lobe epileptogenicity and distinguish between normal and TLE cases. The PSO module was aimed at identifying initial cluster centroids and assigning initial feature weights to cluster centroids and, hence, transferring to the MWK-Means module for the final optimal clustering solution. We demonstrated improvements with the use of the PSO + MWK-Means clustering algorithm compared to that of K-Means and MWK-Means independently. PSO + MWK-Means was able to successfully distinguish between normal and TLE in 97.2% and 82.3% of cases for DTI and MEG data, respectively. It also lateralized left and right TLE in 82.3% and 93.6% of cases for DTI and MEG data, respectively. The proposed optimization and clustering methodology for MEG and DTI features, as they relate to focal epileptogenicity, would enhance the identification of the TLE laterality in cases of unilateral epileptogenicity.

Brain-responsive corticothalamic stimulation in the centromedian nucleus for the treatment of regional neocortical epilepsy.

OBJECTIVE: The aim of the study was to determine if corticothalamic responsive stimulation targeting the centromedian nucleus of the thalamus (CMT) is a potential treatment for neocortical epilepsies with regional onsets. METHODS: We assessed efficacy and safety of CMT and neocortical responsive stimulation, detection, and stimulation programming, methods for implantation, and location and patterns of electrographic seizure onset and spread in 7 patients with medically intractable focal seizures with a regional neocortical onset. RESULTS: The median follow-up duration was 17 months (average: 17 months, range: 8-28 months). The median % reduction in disabling seizures (excludes auras) in the 7 patients was 88% (mean: 80%, range: 55-100%). The median % reduction in all seizure types (disabling + auras) was 73% (mean: 67%, range: 15-94%). There were no adverse events related to implantation of the responsive neurostimulator and leads or related to the delivery of responsive stimulation. Stimulation-related contralateral paresthesias were addressed by adjusting stimulation parameters in the clinic during stimulation testing. Electrographic seizures were detected in the CMT and neocortex in all seven patients. Four patients had simultaneous or near simultaneous seizure onsets in the neocortex and CMT and three had onsets in the neocortex with spread to the CMT. CONCLUSION: In this small series of patients with medically intractable focal seizures and regional neocortical onset, responsive neurostimulation to the neocortex and CMT improved seizure control and was well tolerated. SIGNIFICANCE: Responsive corticothalamic neurostimulation of the CMT and neocortex is a potential treatment for patients with regional neocortical epilepsies.

Leukoaraiosis Predicts Short-term Cognitive But not Motor Recovery in Ischemic Stroke Patients During Rehabilitation.

BACKGROUND: Leukoaraiosis has been shown to impact functional outcomes after acute ischemic stroke. However, its association with domain specific recovery after ischemic stroke is uncertain. We sought to determine whether pre-existing leukoaraiosis is associated with short-term motor and cognitive recovery after stroke. METHODS: We retrospectively studied ischemic stroke patients admitted to acute inpatient rehabilitation (AIR) between January 2013 and September 2015. Patient baseline characteristics, infarct volume, prestroke modified Rankin Scale, stroke cause, rehabilitation length of stay, and Functional Independence Measure (FIM) scores were recorded. Leukoaraiosis severity was graded on brain magnetic resonance imaging using the Fazekas scale. Multiple linear regression was used to determine factors independently associated with the total, cognitive, and motor FIM scores at AIR discharge, respectively. RESULTS: Of 1600 ischemic stroke patients screened, 109 patients were included in the final analysis. After adjustment, the initial National Institute of Health Stroke Scale (ß -0.541, confidence interval [CI] -0.993 to -0.888; P = 0.020) and pre-existing leukoaraiosis severity (ß -1.448, CI -2.861 to -0.034; P = 0.045) independently predicted the total FIM score. Domain specific analysis showed that infarct volume (ß -0.012, CI -0.019 to -0.005; P = 0.002) and leukoaraiosis severity (ß -0.822, CI -1.223 to -0.410; P = 0.0001) independently predicted FIM cognitive scores at discharge from AIR. Leukoaraiosis did not predict FIM motor score (P = 0.17). CONCLUSIONS: Leukoaraiosis severity is an independent predictor of total and cognitive, but not motor FIM scores after AIR for acute ischemic stroke. This highlights that leukoaraiosis affects poststroke recovery in a domain specific fashion, information that may aid counseling of patients and families as well as tailor rehabilitative efforts.

A Comparison of Vagal Nerve Stimulation and Responsive Neurostimulation for the Treatment of Medically Refractory Complex Partial Epilepsy.

BACKGROUND: Neuromodulatory applications such as vagus nerve stimulation (VNS) and responsive neurostimulation (RNS) are safe and effective strategies for medically intractable epilepsy secondary to complex partial seizures, but researchers have yet to compare their efficacies. OBJECTIVE: The goal of this study is to compare VNS and RNS efficacy at reducing seizure frequency and complication rates in subjects with medically intractable epilepsy secondary to complex partial seizures. METHODS: This is a retrospective chart review of 30 patients with medically intractable complex partial epilepsy, who underwent either VNS or RNS placement at a single institution between June 2012 and January 2016. There was a mean follow-up of 19 months. Seizure frequency reduction and complications were identified. RESULTS: The median seizure frequency reduction was similar for VNS (66%) and RNS (58%). There was no major morbidity or mortality, and the frequency of minor complications was similar between VNS (15%) and RNS (18%). CONCLUSION: We found that VNS and RNS reduced the median seizure frequency similarly with no difference in morbidity or mortality. Further prospective studies are warranted as VNS and RNS therapy improves over time.

Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

BACKGROUND: Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. METHODS: Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays. RESULTS: Brain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1ß and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1ß, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus. The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1ß, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group. Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators. CONCLUSIONS: Both brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.

MEG Coherence and DTI Connectivity in mTLE.

Magnetoencephalography (MEG) is a noninvasive imaging method for localization of focal epileptiform activity in patients with epilepsy. Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the relationship between the cerebral functional abnormalities quantified by MEG coherence and structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Resting state MEG data was analyzed using MEG coherence source imaging (MEG-CSI) method to determine the coherence in 54 anatomical sites in 17 adult mTLE patients with surgical resection and Engel class I outcome, and 17 age- and gender- matched controls. DTI tractography identified the fiber tracts passing through these same anatomical sites of the same subjects. Then, DTI nodal degree and laterality index were calculated and compared with the corresponding MEG coherence and laterality index. MEG coherence laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in insular cortex and both lateral orbitofrontal and superior temporal gyri (p < 0.017). Likewise, DTI nodal degree laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p < 0.017). In insular cortex, MEG coherence laterality correlated with DTI nodal degree laterality ([Formula: see text] in the cases of mTLE. None of these anatomical sites showed statistically significant differences in coherence laterality between right and left sides of the controls. Coherence laterality was in agreement with the declared side of epileptogenicity in insular cortex (in 82 % of patients) and both lateral orbitofrontal (88 %) and superior temporal gyri (88 %). Nodal degree laterality was also in agreement with the declared side of epileptogenicity in gyrus rectus (in 88 % of patients), insular cortex (71 %), precuneus (82 %) and superior temporal gyrus (94 %). Combining all significant laterality indices improved the lateralization accuracy to 94 % and 100 % for the coherence and nodal degree laterality indices, respectively. The associated variations in diffusion properties of fiber tracts quantified by DTI and coherence measures quantified by MEG with respect to epileptogenicity possibly reflect the chronic microstructural cerebral changes associated with functional interictal activity. The proposed methodology for using MEG and DTI to investigate diffusion abnormalities related to focal epileptogenicity and propagation may provide a further means of noninvasive lateralization.

Long-term seizure and psychosocial outcomes after resective surgery for intractable epilepsy.

Resective surgery is considered an effective treatment for refractory localization-related epilepsy. Most studies have reported seizure and psychosocial outcomes of 2-5 years postsurgery and a few up to 10 years. Our study aimed to assess long-term (up to 15 years) postsurgical seizure and psychosocial outcomes at our epilepsy center. The Henry Ford Health System Corporate Data Store was accessed to identify patients who had undergone surgical resection for localization-related epilepsy from 1993 to 2011. Demographics including age at epilepsy onset and surgery, seizure frequency before surgery, and pathology were gathered from electronic medical records. Phone surveys were conducted from May 2012 to January 2013 to determine patients' current seizure frequency and psychosocial metrics including driving and employment status and use of antidepressants. Surgical outcomes were based on Engel's classification (classes I and II=favorable outcomes). McNemar's tests, chi-square tests, two sample t-tests, and Wilcoxon two sample tests were used to analyze the relationships of psychosocial and surgical outcomes with demographic and surgical characteristics. A total of 470 patients had resective epilepsy surgery, and of those, 50 (11%) had died since surgery. Of the remaining, 253 (60%) were contacted with mean follow-up of 10.6±5.0years (27% of patients had follow-up of 15 years or longer). Of the patients surveyed, 32% were seizure-free and 75% had a favorable outcome (classes I and II). Favorable outcomes had significant associations with temporal resection (78% temporal vs 58% extratemporal, p=0.01) and when surgery was performed after scalp EEG only (85% vs 65%, p<0.001). Most importantly, favorable and seizure-free outcome rates remained stable after surgery over long-term follow-up [i.e., <5 years (77%, 41%), 5-10 years (67%, 29%), 10-15 years (78%, 38%), and >15 years (78%, 26%)]. Compared to before surgery, patients at the time of the survey were more likely to be driving (51% vs 35%, p<0.001) and using antidepressants (30% vs 22%, p=0.013) but less likely to be working full-time (23% vs 42%, p<0.001). A large majority of patients (92%) considered epilepsy surgery worthwhile regardless of the resection site, and this was associated with favorable outcomes (favorable=98% vs unfavorable=74%, p<0.001). The findings suggest that resective epilepsy surgery yields favorable long-term postoperative seizure and psychosocial outcomes.

Influence of age and location of ictal onset on postoperative outcome in patients with localization-related epilepsy.

INTRODUCTION: Localization-related epilepsy is a significant concern for the middle-aged and older population given the lesser cognitive reserve and the greater likelihood of adverse systemic antiepileptic drug effects. Epilepsy surgery for this age group has the potential for greater postoperative morbidity and mortality, a protracted rehabilitation with its associated economic burden, progressive cognitive and memory decline and a lesser chance of becoming seizure-free after the procedure. METHODS: A retrospective institutional archival review of 120 patients with medically refractory partial epilepsy of both temporal and extratemporal epilepsy was performed. Comparative assessments for seizure cessation and neuropsychological effects were made for those younger and older than 50 years and those with epilepsy durations of greater and less than 20 years. RESULTS: A comparison of surgical outcomes by age group identified that Engel Class I outcomes were attained in 26 of 35 (74%) patients in the older group compared with 49 of 85 (58%) patients in the younger group (p = 0.087). Of the 11 patients aged 60 years or older, 91% attained an Engel Class I outcome, significantly higher than those under 60 years (60%; p = 0.041). Stratification by age of the entire group, otherwise, demonstrated no significant differences by Engel class outcome. Considering both transient and permanent disabilities, the overall complication rate was 14.2% and was similar in patients less than 50 years of age (15.3%) and those aged 50 years or greater (11.4%; p = 0.58). Verbal memory decline was more notable in the older population and for those with epilepsy duration of greater than 20 years. CONCLUSION: This study demonstrates that epilepsy surgery in the older population has similar seizure-free outcomes and complications when compared with younger patients for both mesial temporal and extratemporal origins. Caution regarding postoperative memory decline in the older population must be stressed.

Analysis of scalp EEG and quantitative MRI in cases of temporal lobe epilepsy requiring intracranial electrographic monitoring.

Abstract Purpose. Contradictory scalp electroencephalographic (sEEG) and discordant imaging features are common in temporal lobe epilepsy (TLE). We assessed the relative importance of sEEG features and their relation to quantitative magnetic resonance (MR) imaging measures in regard to surgical outcome. Methods and materials. Patients with a putative TLE underwent extraoperative electrocorticography (eECoG) with bitemporal subdural electrodes for clarification of the ictogenic source. Patients were categorized by sEEG ictal patterns (IPs) as showing unilateral or bilateral onset. Concordance with the side of resection, as determined by eECoG, to that suggested by the predominant sEEG IP was further analysed as: (a) entirely ipsilateral eECoG IPs with discordant nonelectrographic data; (b) ipsilateral preponderant (> 80%) eECoG IPs; and c) contralateral preponderant (> 80%) eECoG IPs. Quantitative hippocampal volumes and signal characteristics were applied for comparison. Results. Of 26 patients, eECoG confirmed a unilateral IP on sEEG in 19 (73%). Of these 19, exclusively ipsilateral sEEG interical epileptiform discharges (IEDs) were identified in 9 (47%). When bilateral, generalized, absent or contralateral IEDs were found, 6 cases (60%) still showed a preponderantly ipsilateral IP identifying the epileptogenic side. In patients with sEEG bilateral IPs, 5 (71%) also had bilateral IEDs. Of the 16 patients who underwent resection, 14 (87.5%) achieved favourable outcomes and 9 (56%), seizure cessation. Hippocampal volumetry in 23 patients correctly lateralized 7 (30%) whereas fluid-attenuated inversion recovery (FLAIR) signal measures applied in 23 patients lateralized 9 (39%). Conclusions. Favourable surgical outcomes are attainable following eECoG in cases where ambiguity exists regarding the laterality of TLE on sEEG, even for those in whom bilateral IPs and either bilateral or no IEDs are demonstrated on sEEG. Neither volumetric nor FLAIR signal ratios were sufficiently reliable for lateralizing TLE in the majority of cases.

Curvature analysis of perisylvian epilepsy.

PURPOSE: We assess whether alterations in the convolutional anatomy of the deep perisylvian area (DPSA) might indicate focal epileptogenicity. MATERIALS AND METHODS: The DPSA of each hemisphere was segmented on MRI and a 3D gray-white matter interface (GWMI) geometrical model was constructed. Comparative visual and quantitative assessment of the convolutional anatomy of both the left and right DPSA models was performed. Both the density of thorn-like contours (peak percentage) and coarse interface curvatures was computed using Gaussian curvature and shape index, respectively. The proposed method was applied to a total of 14 subjects; 7 patients with an epileptogenic DPSA and 7 non-epileptic subjects. RESULTS: A high peak percentage correlated well with the epileptogenic DPSA. It distinguished between patients and non-epileptic subjects (P = 0.029) and identified laterality of the epileptic focus in all but one case. A diminished regional curvature also identified epileptogenicity (P = 0.016) and, moreover, its laterality (P = 0.001). CONCLUSION: An increased peak percentage from a global view of the GWMI of the DPSA provides some indication of a propensity toward a focal or regional DPSA epileptogenicity. A diminished convolutional anatomy (i.e., smoothing effect) appears also to coincide with the epileptogenic site in the DPSA and to distinguish laterality.

The ventral precuneal-posterior cingulate region as a site of epileptogenicity

The ventral precuneal and posterior cingulate area (VP-PC) represents a distinct but topographically variable mesial parietal site of epileptogenicity that may manifest as a common temporal lobe-mediated ictal expression. In a review of records of 62 presumptive epilepsy surgery cases, two cases of primary epileptogenicity expressed within the VP-PC were identified and are detailed to bring attention to this electroencephalographically-hidden area of ictal expression. Details of their investigation and surgical treatment illustrate distinctly different approaches addressing the problem and bringing about a seizure-free outcome.

A Preliminary Study of the Efficacy of Transcranial Direct Current Stimulation in Trigeminal Neuralgia.

The purpose of this study is to assess the efficacy of transcranial direct current stimulation (tDCS) in patients with treatment-refractory trigeminal neuralgia (TN) and examine the utility of neuroimaging methods in identifying markers of such efficacy. Six patients with classical TN refractory to maximal medical treatment, underwent tDCS (three cases inhibitory/cathodic and three cases excitatory/anodic stimulation). All patients underwent pre- and posttreatment functional magnetic resonance imaging (fMRI) during block-design tasks (i.e., Pain, Pain + tDCS, tDCS) as well as single-shell diffusion MRI (dMRI) acquisition. The precise locations of tDCS electrodes were identified by neuronavigation. Five therapeutic tDCS sessions were carried out for each patient with either anodic or cathodic applications. The Numeric Rating Scale of pain (NRS) and the Headache Disability Index (HDI) were used to score the subjective efficacy of treatment. Altered activity of regional sites was identified by fMRI and associated changes in the spinothalamocortical sensory tract (STCT) were measured by the dMRI indices of fractional anisotropy (FA) and mean diffusivity (MD). Fiber counts of the bilateral trigeminal root entry zone (REZ) were performed as an added measure of fiber loss or recovery. All patients experienced a significant reduction in pain scores with a substantial decline in HDI (P value < 0.01). Following a course of anodic tDCS, the ipsilateral caudate, globus pallidus, somatosensory cortex, and the contralateral globus pallidus showed a significantly attenuated activation whereas cathodic tDCS treatment resulted in attenuation of the thalamus and globus pallidus bilaterally, and the somatosensory cortex and anterior cingulate gyrus contralaterally. dMRI analysis identified a substantial increase (>50%) in the number of contralateral sensory fibers in the STCT with either anodic or cathodic tDCS treatment in four of the six patients. A significant reduction in FA (>40%) was observed in the ipsilateral REZ in the posttreatment phase in five of the six patients. Preliminary evidence suggests that navigated tDCS presents a promising method for alleviating the pain of TN. Different patterns of activation manifested by anodic and cathodic stimulation require further elaboration to understand their implication. Activation and attenuation of responses at various sites may provide further avenues for condition treatment.

Hippocampal volumetry for lateralization of temporal lobe epilepsy: automated versus manual methods.

The hippocampus has been the primary region of interest in the preoperative imaging investigations of mesial temporal lobe epilepsy (mTLE). Hippocampal imaging and electroencephalographic features may be sufficient in several cases to declare the epileptogenic focus. In particular, hippocampal atrophy, as appreciated on T1-weighted (T1W) magnetic resonance (MR) images, may suggest a mesial temporal sclerosis. Qualitative visual assessment of hippocampal volume, however, is influenced by head position in the magnet and the amount of atrophy in different parts of the hippocampus. An entropy-based segmentation algorithm for subcortical brain structures (LocalInfo) was developed and supplemented by both a new multiple atlas strategy and a free-form deformation step to capture structural variability. Manually segmented T1-weighted magnetic resonance (MR) images of 10 non-epileptic subjects were used as atlases for the proposed automatic segmentation protocol which was applied to a cohort of 46 mTLE patients. The segmentation and lateralization accuracies of the proposed technique were compared with those of two other available programs, HAMMER and FreeSurfer, in addition to the manual method. The Dice coefficient for the proposed method was 11% (p<10(-5)) and 14% (p<10(-4)) higher in comparison with the HAMMER and FreeSurfer, respectively. Mean and Hausdorff distances in the proposed method were also 14% (p<0.2) and 26% (p<10(-3)) lower in comparison with HAMMER and 8% (p<0.8) and 48% (p<10(-5)) lower in comparison with FreeSurfer, respectively. LocalInfo proved to have higher concordance (87%) with the manual segmentation method than either HAMMER (85%) or FreeSurfer (83%). The accuracy of lateralization by volumetry in this study with LocalInfo was 74% compared to 78% with the manual segmentation method. LocalInfo yields a closer approximation to that of manual segmentation and may therefore prove to be more reliable than currently published automatic segmentation algorithms.

An assessment of MEG coherence imaging in the study of temporal lobe epilepsy.

PURPOSE: This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug-resistant temporal lobe epilepsy (TLE). METHODS: An archival review of ECD MEG analyses of 30 presurgical patients with TLE was undertaken with data extracted subsequently for coherence analysis by a blinded reviewer for comparison of accuracy of lateralization. Postoperative outcome was assessed by Engel classification. MEG coherence images were generated from 10 min of spontaneous brain activity and compared to surgically resected brain areas outlined on each subject's magnetic resonance image (MRI). Coherence values were averaged independently for each hemisphere to ascertain the laterality of the epileptic network. Reliability between runs was established by calculating the correlation between epochs. Match rates compared the results of each of the two MEG analyses with optimal postoperative outcome. KEY FINDINGS: The ECD method provided an overall match rate of 50% (13/16 cases) for Engel class I outcomes, with 37% (11/30 cases) found to be indeterminate (i.e., no spikes identified on MEG). Coherence analysis provided an overall match rate of 77% (20/26 cases). Of 19 cases without evidence of mesial temporal sclerosis, coherence analysis correctly lateralized the side of TLE in 11 cases (58%). Sensitivity of the ECD method was 41% (indeterminate cases included) and that of the coherence method 73%, with a positive predictive value of 70% for an Engel class Ia outcome. Intrasubject coherence imaging reliability was consistent from run-to-run (correlation > 0.90) using three 10-min epochs. SIGNIFICANCE: MEG coherence analysis has greater sensitivity than the ECD method for lateralizing TLE and demonstrates reliable stability from run-to-run. It, therefore, improves upon the capability of MEG in providing further information of use in clinical decision-making where the laterality of TLE is questioned.

Ictal barking as a manifestation of temporal lobe epilepsy.

Ictal nonspeech vocalizations have been described as manifestations of either frontal or temporal epileptogenicity originating mainly from the dominant hemisphere. Ictal barking, particularly, has been considered a manifestation of mesial frontal epilepsy. A 42-year-old right-handed male with posttraumatic drug-resistant complex partial epilepsy manifested ictal barking near electrographic onset. Extraoperative electrocorticography with subdural electrode coverage of the right frontoparietal and temporal and left frontal surfaces provided surveillance of ictal origin and propagation. Ictal origin was identified in the right mesial temporal lobe with barking vocalization manifesting within 3s of electrographic onset. No subsequent spread of activity was noted beyond the temporal lobe. Resection of the mesial temporal structure resulted in seizure freedom. Pathology identified hippocampal sclerosis. This case supports the notion that an intrinsic, intralobar epileptogenic neural network in either hemisphere can act as a conduit into the limbic and memory circuits without a laterality bias to manifest as barking.

Prospective Quantitative Neuroimaging Analysis of Putative Temporal Lobe Epilepsy.

Purpose: A prospective study of individual and combined quantitative imaging applications for lateralizing epileptogenicity was performed in a cohort of consecutive patients with a putative diagnosis of mesial temporal lobe epilepsy (mTLE). Methods: Quantitative metrics were applied to MRI and nuclear medicine imaging studies as part of a comprehensive presurgical investigation. The neuroimaging analytics were conducted remotely to remove bias. All quantitative lateralizing tools were trained using a separate dataset. Outcomes were determined after 2 years. Of those treated, some underwent resection, and others were implanted with a responsive neurostimulation (RNS) device. Results: Forty-eight consecutive cases underwent evaluation using nine attributes of individual or combinations of neuroimaging modalities: 1) hippocampal volume, 2) FLAIR signal, 3) PET profile, 4) multistructural analysis (MSA), 5) multimodal model analysis (MMM), 6) DTI uncertainty analysis, 7) DTI connectivity, and 9) fMRI connectivity. Of the 24 patients undergoing resection, MSA, MMM, and PET proved most effective in predicting an Engel class 1 outcome (>80% accuracy). Both hippocampal volume and FLAIR signal analysis showed 76% and 69% concordance with an Engel class 1 outcome, respectively. Conclusion: Quantitative multimodal neuroimaging in the context of a putative mTLE aids in declaring laterality. The degree to which there is disagreement among the various quantitative neuroimaging metrics will judge whether epileptogenicity can be confined sufficiently to a particular temporal lobe to warrant further study and choice of therapy. Prediction models will improve with continued exploration of combined optimal neuroimaging metrics.

FLAIR signal and texture analysis for lateralizing mesial temporal lobe epilepsy.

Standard magnetic resonance (MR) imaging analysis in several cases of mesial temporal lobe epilepsy (mTLE) either fail to show an identifiable hippocampal asymmetry or provide only subtle distinguishing features that remain inconclusive. A retrospective analysis of hippocampal fluid-attenuated inversion recovery (FLAIR) MR images was performed in cases of mTLE addressing, particularly, the mean and standard deviation of the signal and its texture. Preoperative T1-weighted and FLAIR MR images of 25 nonepileptic control subjects and 36 mTLE patients with Engel class Ia outcomes were analyzed. Patients requiring extraoperative electrocorticography (ECoG) with intracranial electrodes and thus judged to be more challenging were studied as a separate cohort. Hippocampi were manually segmented on T1-weighted images and their outlines were transposed onto FLAIR studies using an affine registration. Image intensity features including mean and standard deviation and wavelet-based texture features were determined for the hippocampal body. The right/left ratios of these features were used with a linear classifier to establish laterality. Whole hippocampal within-subject volume ratios were assessed for comparison. Mean and standard deviation of FLAIR signal intensities lateralized the site of epileptogenicity in 98% of all cases, whereas analysis of wavelet texture features and hippocampal volumetry each yielded correct lateralization in 94% and 83% of cases, respectively. Of patients requiring more intensive study with extraoperative ECoG, 17/18 were lateralized effectively by the combination of mean and standard deviation ratios despite a ratio of mean signal intensity near one in some. The analysis of mean and standard deviation of FLAIR signal intensities provides a highly sensitive method for lateralizing the epileptic focus in mTLE over that of volumetry or texture analysis of the hippocampal body.

Review of current microsurgical management of insular gliomas.

The insular lobe is a functionally complex structure, harbouring peculiar anatomical and vascular features and specific neuronal connectivity with surrounding cerebral structures. It is situated in the depth of the Sylvian fissure and can be affected by either low-grade or high-grade gliomas. Because of its complexity, surgery of insular tumours has been traditionally regarded as hazardous. Nonetheless, currently improved diagnostic, neurophysiological and surgical tools allow the neurosurgeon to perform surgery of insular gliomas in a safer way, thus bringing forward the pioneering work performed by neurosurgeons in the past two decades.The aim of this paper is to provide the reader with an updated review of the anatomy, the clinical picture, diagnosis and surgical management of insular gliomas.

Multimodal data analysis of epileptic EEG and rs-fMRI via deep learning and edge computing.

BACKGROUND AND OBJECTIVE: Multimodal data analysis and large-scale computational capability is entering medicine in an accelerative fashion and has begun to influence investigational work in a variety of disciplines. It is also informing us of therapeutic interventions that will come about with such development. Epilepsy is a chronic brain disorder in which functional changes may precede structural ones and which may be detectable using existing modalities. METHODS: Functional connectivity analysis using electroencephalography (EEG) and resting state-functional magnetic resonance imaging (rs-fMRI) has provided such meaningful input in cases of epilepsy. By leveraging the potential of autonomic edge computing in epilepsy, we develop and deploy both noninvasive and invasive methods for monitoring, evaluation, and regulation of the epileptic brain. First, an autonomic edge computing framework is proposed for the processing of big data as part of a decision support system for surgical candidacy. Second, a multimodal data analysis using independently acquired EEG and rs-fMRI is presented for estimation and prediction of the epileptogenic network. Third, an unsupervised feature extraction model is developed for EEG analysis and seizure prediction based on a Convolutional deep learning (CNN) structure for distinguishing preictal (pre-seizure) state from non-preictal periods by support vector machine (SVM) classifier. RESULTS: Experimental and simulation results from actual patient data validate the effectiveness of the proposed methods. CONCLUSIONS: The combination of rs-fMRI and EEG/iEEG can reveal more information about dynamic functional connectivity. However, simultaneous fMRI and EEG data acquisition present challenges. We have proposed system models for leveraging and processing independently acquired fMRI and EEG data.