Intractable Mesial Temporal Lobe Epilepsy Research Articles

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Intracranial Neurofeedback Modulating Neural Activity in the Mesial Temporal Lobe During Memory Encoding: A Pilot Study

Removal of the mesial temporal lobe (MTL) is an established surgical procedure that leads to seizure freedom in patients with intractable MTL epilepsy; however, it carries the potential risk of memory damage. Neurofeedback (NF), which regulates brain function by converting brain activity into perceptible information and providing feedback, has attracted considerable attention in recent years for its potential as a novel complementary treatment for many neurological disorders. However, no research has attempted to artificially reorganize memory functions by applying NF before resective surgery to preserve memory functions. Thus, this study aimed (1) to construct a memory NF system that used intracranial electrodes to feedback neural activity on the language-dominant side of the MTL during memory encoding and (2) to verify whether neural activity and memory function in the MTL change with NF training. Two intractable epilepsy patients with implanted intracranial electrodes underwent at least five sessions of memory NF training to increase the theta power in the MTL. There was an increase in theta power and a decrease in fast beta and gamma powers in one of the patients in the late stage of memory NF sessions. NF signals were not correlated with memory function. Despite its limitations as a pilot study, to our best knowledge, this study is the first to report that intracranial NF may modulate neural activity in the MTL, which is involved in memory encoding. The findings provide important insights into the future development of NF systems for the artificial reorganization of memory functions.

Multifocal hypometabolic correlates to deficits of verbal memory in mesial temporal lobe epilepsy

Background and ObjectivesNeuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory in these patients. Our study evaluated the pathophysiology behind verbal learning/memory deficits as revealed by hypometabolism quantified through 18-fluorodeoxyglucose positron emission tomography (FDG-PET). MethodsThis retrospective study included thirty presurgical patients with intractable unilateral MTLE who underwent interictal FDG-PET and verbal memory assessment (12 females, mean age: 38.73 years). Fluorodeoxyglucose-positron emission tomography mapping was performed with voxel-based mapping of glucose utilization to a database of age-matched controls to derive regional Z-scores. Neuropsychological outcome variables included scores on learning and recall trials of two distinct verbal memory measures validated for use in epilepsy research. Pearson’s correlations evaluated relationships between clinical variables and verbal memory. Linear regression was used to relate regional hypometabolism and verbal memory assessment. Post hoc analyses assessed areas of FDG-PET hypometabolism (threshold Z ≤ −1.645 below mean) where verbal memory was impaired. ResultsVerbal memory deficits correlated with hypometabolism in limbic structures ipsilateral to language dominance but also correlated with hypometabolism in networks involving the ipsilateral perisylvian cortex and contralateral limbic and nonlimbic structures. DiscussionWe conclude that traditional models of verbal memory may not adequately capture cognitive deficits in a broader sample of patients with MTLE. This study has important implications for epilepsy surgery protocols that use neuropsychological data and FDG-PET to draw conclusions about surgical risks.

Epilepsy surgery for dominant-side mesial temporal lobe epilepsy without hippocampal sclerosis

Although anterior temporal lobectomy (ATL) is an established surgery for medically intractable mesial temporal lobe epilepsy (MTLE), it can harm memory function, especially in dominant-side MTLE patients without hippocampal sclerosis (HS). To avoid this complication, multiple hippocampal transection (MHT) was developed, but its efficacy has not been fully elucidated. We report the detailed treatment results of MHT compared with that of ATL. We retrospectively analysed the records of 30 patients who underwent surgery for dominant-side MTLE. ATL was completed for 23 patients with HS, and MHT was completed for 7 patients without HS. The seizure control status, number of anti-seizure medicines, neurocognitive function, and psychiatric disorders of each patient were reviewed. The mean follow-up period was 70 months. Seizure control of Engel class I was achieved in 16 patients (70%) in the ALT group versus 5 patients (71%) in the MHT group. The mean number of anti-seizure medicines administered in the ATL group changed significantly from 2.4 to 1.9 (p = 0.01), while that in the MHT group was unchanged (from 2.1 to 2.0, p = 0.77). Eleven patients (48%) in the ATL group developed psychiatric disorders during the postoperative follow-up period, whereas no psychological complications were observed in the MHT group. Neither group showed neurocognitive decline after the surgery in any of the WAIS-III or WMS-R subtests. In conclusion, MHT may achieve reasonable postoperative seizure reduction, preserve neurocognitive function, and reduce postoperative psychiatric complications. Therefore, it can be considered as a therapeutic option for dominant-side MTLE without HS.

Transcortical selective amygdalohippocampectomy for intractable mesial temporal lobe epilepsy: a review of outcomes in a single center

Introduction: Various surgical procedures have been found to effectively treat intractable temporal lobe epilepsy (TLE), including transcortical selective amygdalohippocampectomy (SAH), which is intended to protect the temporal lobe and to prevent interference with vascular structure. This research analyzed the outcome of post-operative seizure-free with transcortical selective amygdalohippocampectomy for intractable mesial temporal lobe epilepsy patients in a minimum two-year follow-up after surgery. Methods: Data of one hundred ninety-two patients who had undergone transcortical selective amygdalohippocampectomy for non-lesional, medically intractable, temporal lobe epilepsy were analyzed. Result: The statistical analysis indicated that Focal to Bilateral Tonic-Clonic Seizure had a more significant outcome (p=0.019) than other seizures. In all research subjects, after three, six, and twelve years of follow-up, the chance for a seizure-free after surgery was respectively 93.2 percent, 67.9 percent, and 36.7 percent with a median average survival period for all subjects of 11.00 years (95 % CI: 8.55 – 13.44) Conclusions: Transcortical selective amygdalohippocampectomy is an effective therapy for intractable mesial temporal lobe epilepsy and provides a satisfactory outcome. The transcortical approach allows an appropriate operative field by careful dissection with limited retraction to eliminate the epileptogenic target while preventing damage to the underlying vascular and cortical structures.

Dynamical Analysis of Seizure in Epileptic Brain: a Dynamic Phase-Amplitude Coupling Estimation Approach.

Cross-frequency coupling in general and phase-amplitude coupling (PAC) as a particular form of it, provides an opportunity to investigate the complex interactions between neural oscillations in the human brain and neurological disorders such as epilepsy. Using PAC detection methods on temporal sliding windows, we developed a map of dynamic PAC evolution to investigate the spatiotemporal changes occurring during ictal transitions in a patient with intractable mesial temporal lobe epilepsy. The map is built by computing the modulation index between the amplitude of high frequency oscillations and the phase of lower frequency rhythms from the intracranial stereoelectroencephalography recordings during seizure. Our preliminary results show early abnormal PAC changes occurring in the preictal state prior to the occurrence of clinical or visible electrographic seizure onset, and suggest that dynamic PAC measures may serve as a potential clinical technique for analyzing seizure dynamics.Clinical Relevance-Application of a dynamic temporal PAC map as a new tool may provide novel insights into the neurophysiology of epileptic seizure activity and its spatio-temporal dynamics.

Different Functional Network Connectivity Patterns in Epilepsy: A Rest-State fMRI Study on Mesial Temporal Lobe Epilepsy and Benign Epilepsy With Centrotemporal Spike.

The stark discrepancy in the prognosis of epilepsy is closely related to brain damage features and underlying mechanisms, which have not yet been unraveled. In this study, differences in the epileptic brain functional connectivity states were explored through a network-based connectivity analysis between intractable mesial temporal lobe epilepsy (MTLE) patients and benign epilepsy with centrotemporal spikes (BECT). Resting state fMRI imaging data were collected for 14 MTLE patients, 12 BECT patients and 16 healthy controls (HCs). Independent component analysis (ICA) was performed to identify the cortical functional networks. Subcortical nuclei of interest were extracted from the Harvard-Oxford probability atlas. Network-based statistics were used to detect functional connectivity (FC) alterations across intranetworks and internetworks, including the connectivity between cortical networks and subcortical nuclei. Compared with HCs, MTLE patients showed significant lower activity between the connectivity of cortical networks and subcortical nuclei (especially hippocampus) and lower internetwork FC involving the lateral temporal lobe; BECT patients showed normal cortical-subcortical FC with hyperconnectivity between cortical networks. Together, cortical-subcortical hypoconnectivity in MTLE suggested a low efficiency and collaborative network pattern, and this might be relevant to the final decompensatory state and the intractable prognosis. Conversely, cortical-subcortical region with normal connectivity remained well in global cooperativity, and compensatory internetwork hyperconnectivity caused by widespread cortical abnormal discharge, which might account for the self-limited clinical outcome in BECT. Based on the fMRI functional network study, different brain network patterns might provide a better explanation of mechanisms in different types of epilepsy.

Comparison of the keyhole trans-middle temporal gyrus approach and transsylvian approach for selective amygdalohippocampectomy: A single-center experience

Several approach routes exist for selective amygdalohippocampectomy (SAH); however, previous reports regarding a comparison of these routes are limited. Here, we compared trans-middle temporal gyrus (T2) SAH and transsylvian (TS) SAH in terms of seizure outcome, visual-field defect, memory function, and operation time in our institution. This retrospective study examined the data of 16 patients with medically intractable mesial temporal lobe epilepsy. Six patients underwent trans-T2 SAH and 10 patients underwent TS SAH between July 2014 and February 2019 in Osaka City University Hospital. In trans-T2 SAH, we performed a keyhole temporal craniotomy and a small corticotomy on T2. In TS SAH, we performed a 1.5 cm corticotomy along the inferior periinsular sulcus after opening the sylvian fissure. Amygdalohippocampectomy after reaching the inferior horn of the lateral ventricle was performed in the same manner in both procedures. The seizure outcome, visual-field defect, memory function, and operation time were retrospectively compared between the procedures. Seizure-free outcomes were achieved for six patients in the trans-T2 SAH and eight patients in the TS SAH group. There were no significant differences in the seizure outcome, visual-field defect, and memory function. The operation time was significantly shorter for trans-T2 SAH than TS SAH. The postoperative scar was less conspicuous for trans-T2 SAH. Trans-T2 SAH and TS SAH were comparable in terms of the seizure outcome, visual-field defect, and memory function. The operation time and length of the skin incision were shorter for trans-T2 SAH, suggesting that it may be preferable for general epilepsy surgeons.

Minimally Invasive Technique (Nummular Craniotomy) for Mesial Temporal Lobe Epilepsy: A Comparison of 2 Approaches

To describe our series of a minimally invasive technique using a small scalp incision and keyhole craniotomy for the removal of mesial temporal lobe structures through a transcortical approach in patients with medically intractable mesial temporal lobe epilepsy (MTLE). Studies that directly compare the clinical outcomes between minimally invasive and conventional techniques are scarce, and this information is lacking in the literature. The study enrolled 73 consecutive patients with refractory MTLE and unilateral hippocampal sclerosis; 30 patients were operated on with standard frontotemporal craniotomy between 2010 and 2013 and 43 patients were operated with a minimally invasive craniotomy (nummular craniotomy) between 2014 and 2016. The preoperative evaluation included clinical history, physical examination, video-electroencephalography, neuropsychologic assessment, and magnetic resonance imaging including thin-section coronal sequences. There were no deaths in either group. Postoperative complications in the standard frontotemporal craniotomy group included temporal muscle atrophy (n= 4; 13.3%), cerebrospinal fluid leakage (n= 1; 3.3%), and wound infection (n= 1; 3.3%). No complications were observed in the keyhole craniotomy group. There was no between-group difference in postoperative seizure control. The mean Engel class I seizure-free outcome was 90.4% in the standard frontotemporal craniotomy group and 90.7% in the nummular craniotomy group (P > 0.05). Lengths of hospitalization (2.81 vs. 4.37 days, P < 0.001) and operative time (85.79 vs. 142.73 minutes, P < 0.001) were lower in the keyhole than in the standard frontotemporal craniotomy group, respectively. The nummular technique was associated with faster recovery, early hospital discharge, and fewer complications than the standard technique. No differences were observed in postoperative seizure control. Keyhole craniotomy is a safe, easy, and effective treatment option for medically intractable MTLE.

Long-term Outcomes in Patients with Intractable Mesial Temporal Lobe Epilepsy who Undergo Laser Ablation. (P5.5-019)

Long-term Outcomes in Patients with Intractable Mesial Temporal Lobe Epilepsy who Undergo Laser Ablation. (P5.5-019)

Cell injury and receptor expression in the epileptic human amygdala

Neuropathological findings in the amygdala obtained from patients with mesial temporal lobe epilepsy (MTLE) indicate varying degrees of histopathological alterations, such as neuronal loss and gliosis. The mechanisms underlying cellular damage in the amygdala of patients with MTLE have not been fully elucidated. In the present study, we assess cellular damage, determine the receptor expression of major inhibitory and excitatory neurotransmitters, and evaluate the correlation between the expression of various receptors and cell damage in the basolateral complex and the centromedial areas in the amygdala specimens resected during brain surgery on 30 patients with medically intractable MTLE. Our data reveal an increased rate of cell damage and apoptosis as well as decreased expression levels of several GABAergic receptor subunits (GABAARα1, GABAARβ3, and GABABR1) and GAD65 in the amygdalae obtained during epilepsy surgery compared to autopsy specimens. Analyses of the expression of glutamate excitatory receptor subunits (NR1, NR2B, mGluR1α, GluR1, and GluR2) reveal no significant differences between the epileptic amygdalae and autopsy control tissues. Furthermore, the increased occurrence of apoptotic cells in the amygdala is negatively correlated with the reduced expression of the studied GABAergic receptor subunits and GAD65 but is not correlated with the expression of excitatory receptors. The present data point to the importance of GABAergic neurotransmission in seizure-induced cell injury in the amygdala of patients with MTLE and suggest several GABA receptor subunits as potential druggable target structures to control epilepsy and its comorbid disorders, such as anxiety.

Epilepsy surgery for a patient with neurofibromatosis type 1 concomitant with moyamoya syndrome

BackgroundEpilepsy associated with neurocutaneous disorders is well known, and the prevalence of epilepsy among patients with neurofibromatosis type 1 (NF1) ranges from 4% to 13%. However, epilepsy surgery for patients with NF1 is not commonly performed. Case descriptionWe report the case of a patient with medically intractable mesial temporal lobe epilepsy (mTLE) concomitant NF1 and moyamoya syndrome (MMS) who had already undergone bilateral superficial temporal artery-middle cerebral artery anastomosis at 17 years old. As the standard temporal approach was unavailable, we evaluated the patient with neurologists, radiologists, neurosurgeons and neuropsychologists to identify the safest trajectory for epilepsy surgery. The patient underwent the right selective amygdala hippocampectomy from the posterior auricle part at 32 years old and obtained freedom from seizures. ConclusionTo the best of our knowledge, this represents the first surgical case report for mTLE concomitant with NF1 and MMS.

Laser interstitial thermal therapy (LITT): Seizure outcomes for refractory mesial temporal lobe epilepsy

BackgroundLaser interstitial thermal therapy (LITT) is a minimally invasive alternative with less cognitive risks compared with traditional surgery for focal drug-resistant epilepsy. ObjectiveWe describe seizure outcomes and complications after LITT in our cohort with intractable mesial temporal lobe epilepsy (MTLE). Material and methodsWe prospectively tracked Stanford's MTLE cases treated with LITT from October 2014 to October 2017. Primary endpoints were seizure outcomes by (1) Engel classification and (2) reduction in baseline seizure frequency. Secondary outcomes were postablation complications. ResultsA total of 30 patients underwent selective amygdalohippocampotomy via LITT. Mesial temporal sclerosis (MTS) was present in 23/30 (77%) patients. Median follow-up was 18 ± 12 months (range: 6–44 months). Almost all 28/29 (97%) patients had >50% reduction, and 22/29 (76%) patients had >90% reduction in seizure frequency. Engel Class I outcome was achieved in 18/29 (62%) patients; with complete seizure freedom in 9/29 (31%) patients (Engel Class IA). Three (10%) patients have had only focal aware seizures (Engel Class 1B). Seizures only occurred with medication withdrawal in 6/29 (21%) patients (Engel Class ID). Class II was achieved by 6/29 (21%) and Class III by 5/29 (17%) patients.Complications included perioperative seizures in 10/29 (34%) and nonseizure complaints in 6/29 (21%) patients. Three (10%) patients had neurological deficits including one permanent superior quadrantanopsia, one transient trochlear, and one transient oculomotor nerve palsy. ConclusionsOverall, Engel Class I outcome was achieved in 62% of patients with MTLE, and 97% of patients achieved >50% seizure frequency reduction. Complications were largely temporary, though there was one persistent visual field deficit. Laser ablation is well-tolerated and offers marked seizure reduction for the majority of patients.

[Seizure outcome after surgery for medically intractable mesial temporal lobe epilepsy and its predictors].

To evaluate seizure outcome in patients receiving surgery for chronic medically intractable mesial temporal lobe epilepsy (MTLE) and analyze its possible predictors. This retrospective study was conducted in patients with chronic medically intractable MTLE undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) in our department between September, 2011 and October, 2013. The patients were followed up for 3.5 to 5.5 years, during which the seizure outcome was evaluated according to Engel's classification. The clinical data were collected from the patients to identify the possible predictors that affected the outcome of the patients using Mann-Whitney U test or Kruskal-Wallis test. Atotal of 34 patients were included in this study with a definite diagnosis of chronic medically intractable MTLE after preoperative noninvasive and invasive evaluation. In 4 of these patients, invasive EEG monitoring confirmed that epileptic discharges originated from the bilateral mesial temporal lobe, and hence surgical resection of the epileptogenic zone was not performed. The other 30 patients underwent surgical resection of the epileptogenic zone with ALT or SAH, and favorable outcomes were achieved in 23 (76.7%) of the patients. Of the 7 (23.3%) patients with poor outcomes, 6 patients presented with typical automatism and aura with frequent secondary generalized tonic-clonic seizure, and the other one patient exhibited impaired intelligence. Statistical analysis suggested that the patients without a special disease history (trauma, febrile seizure, or encephalitis) tended to have a more favorable seizure outcome. Surgical interventions can achieve good therapeutic effect on chronic medically intractable MTLE, and patients without a special disease history may have more favorable outcomes after the surgery. SAH via the superior temporal sulcus approach can be a better surgical option for intractable MTLE.

Laser ablation for mesial temporal epilepsy: a multi-site, single institutional series.

OBJECTIVEAlthough it is still early in its application, laser interstitial thermal therapy (LiTT) has increasingly been employed as a surgical option for patients with mesial temporal lobe epilepsy. This study aimed to describe mesial temporal lobe ablation volumes and seizure outcomes following LiTT across the Mayo Clinic's 3 epilepsy surgery centers.METHODSThis was a multi-site, single-institution, retrospective review of seizure outcomes and ablation volumes following LiTT for medically intractable mesial temporal lobe epilepsy between October 2011 and October 2015. Pre-ablation and post-ablation follow-up volumes of the hippocampus were measured using FreeSurfer, and the volume of ablated tissue was also measured on intraoperative MRI using a supervised spline-based edge detection algorithm. To determine seizure outcomes, results were compared between those patients who were seizure free and those who continued to experience seizures.RESULTSThere were 23 patients who underwent mesial temporal LiTT within the study period. Fifteen patients (65%) had left-sided procedures. The median follow-up was 34 months (range 12-70 months). The mean ablation volume was 6888 mm3. Median hippocampal ablation was 65%, with a median amygdala ablation of 43%. At last follow-up, 11 (48%) of these patients were seizure free. There was no correlation between ablation volume and seizure freedom (p = 0.69). There was also no correlation between percent ablation of the amygdala (p = 0.28) or hippocampus (p = 0.82) and seizure outcomes. Twelve patients underwent formal testing with computational visual fields. Visual field changes were seen in 67% of patients who underwent testing. Comparing the 5 patients with clinically noticeable visual field deficits to the rest of the cohort showed no significant difference in ablation volume between those patients with visual field deficits and those without (p = 0.94). There were 11 patients with follow-up neuropsychological testing. Within this group, verbal learning retention was 76% in the patients with left-sided procedures and 89% in those with right-sided procedures.CONCLUSIONSIn this study, there was no significant correlation between the ablation volume after LiTT and seizure outcomes. Visual field deficits were common in formally tested patients, much as in patients treated with open temporal lobectomy. Further studies are required to determine the role of amygdalohippocampal ablation.

Surgical Considerations of Intractable Mesial Temporal Lobe Epilepsy.

Surgery of temporal lobe epilepsy is the best opportunity for seizure freedom in medically intractable patients. The surgical approach has evolved to recognize the paramount importance of the mesial temporal structures in the majority of patients with temporal lobe epilepsy who have a seizure origin in the mesial temporal structures. For those individuals with medically intractable mesial temporal lobe epilepsy, a selective amygdalohippocampectomy surgery can be done that provides an excellent opportunity for seizure freedom and limits the resection to temporal lobe structures primarily involved in seizure genesis.

A right amygdalohippocampectomy: A diagnostic challenge

ObjectiveAmygdalohippocampectomy (AHE) is the resective surgery for medically intractable mesial temporal lobe epilepsy. To date no study has investigated a wide range of neuropsychiatric symptoms in right AHE outpatients. Patients and methodsThree patients with right AHE participated in this study. The control group are patients with cognitive complaints with no history of epilepsy or neurological impairment and no structural abnormalities on the MRI/CT. We expected no difference in verbal memory compared to the controls. Concerning affective Theory of Mind (ToM) we expect a difference between controls and AHE patients. In terms of behavior it is expected that coping and behavioral questionnaires do not significantly differ between AHE and controls, but that proxies of AHE patients do report more behavioral/psychiatric symptoms. ResultsNo significant difference was found between groups concerning the cognitive functions. For affective ToM we did find a significant difference (p=0.044). A significant difference for the use of more reassuring thoughts (p=0.006) and a trend for less passive reactions on the coping questionnaire, suggesting an ‘active coping style’. Overall, AHE patients report fewer problems the self- reported questionnaires. Proxies of the AHE patients reported a trend for more behavioral disinhibition compared to proxy ratings of the control group. ConclusionRight AHE patients underestimate their behavioral and emotional changes due to self-awareness deficits. Ratings of significant others are of immense importance for the detection of psychiatric and behavioral problems. Lesions in the amygdala- orbitofrontal cortex connection disrupt the emotional network, which might explain our results.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1± (standard deviation) 2.2years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6months or longer, and 15% experienced at least one seizure-free period of 1year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Magnetoencephalography with temporal spread imaging to visualize propagation of epileptic activity.

We describe temporal spread imaging (TSI) that can identify the spatiotemporal pattern of epileptic activity using Magnetoencephalography (MEG). A three-dimensional grid of voxels covering the brain is created. The array-gain minimum-variance spatial filter is applied to an interictal spike to estimate the magnitude of the source and the time (Ta) when the magnitude exceeds a predefined threshold at each voxel. This calculation is performed through all spikes. Each voxel has the mean Ta (<Ta>) and spike number (Nsp), which is the number of spikes whose source exceeds the threshold. Then, a random resampling method is used to determine the cutoff value of Nsp for the statistically reproducible pattern of the activity. Finally, all the voxels where the source exceeds the threshold reproducibly shown on the MRI with a color scale representing <Ta>. Four patients with intractable mesial temporal lobe epilepsy (MTLE) were analyzed. In three patients, the common pattern of the overlap between the propagation and the hypometabolism shown by fluorodeoxyglucose-positron emission tomography (FDG-PET) was identified. TSI can visualize statistically reproducible patterns of the temporal and spatial spread of epileptic activity. TSI can assess the statistical significance of the spatiotemporal pattern based on its reproducibility.

Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy.

To describe mesial temporal lobe ablated volumes, verbal memory, and surgical outcomes in patients with medically intractable mesial temporal lobe epilepsy (mTLE) treated with magnetic resonance imaging (MRI)-guided stereotactic laser interstitial thermal therapy (LiTT). We prospectively tracked seizure outcome in 20 patients at Thomas Jefferson University Hospital with drug-resistant mTLE who underwent MRI-guided LiTT from December 2011 to December 2014. Surgical outcome was assessed at 6 months, 1 year, 2 years, and at the most recent visit. Volume-based analysis of ablated mesial temporal structures was conducted in 17 patients with mesial temporal sclerosis (MTS) and results were compared between the seizure-free and not seizure-free groups. Following LiTT, proportions of patients who were free of seizures impairing consciousness (including those with auras only) are as follows: 8 of 15 patients (53%, 95% confidence interval [CI] 30.1-75.2%) after 6 months, 4 of 11 patients (36.4%, 95% CI 14.9-64.8%) after 1 year, 3 of 5 patients (60%, 95% CI 22.9-88.4%) at 2-year follow-up. Median follow-up was 13.4 months after LiTT (range 1.3 months to 3.2 years). Seizure outcome after LiTT suggests an all or none response. Four patients had anterior temporal lobectomy (ATL) after LiTT; three are seizure-free. There were no differences in total ablated volume of the amygdalohippocampus complex or individual volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus between seizure-free and non-seizure-free patients. Contextual verbal memory performance was preserved after LiTT, although decline in noncontextual memory task scores were noted. We conclude that MRI-guided stereotactic LiTT is a safe alternative to ATL in patients with medically intractable mTLE. Individualized assessment is warranted to determine whether the reduced odds of seizure freedom are worth the reduction in risk, discomfort, and recovery time. Larger prospective studies are needed to confirm our preliminary findings, and to define optimal ablation volume and ideal structures for ablation.