Bilateral Mesial Temporal Lobe Epilepsy Research Articles

Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy

ObjectivePharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. MethodsOur enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. ResultsWe terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ± 2.67 (median 3.0 [IQR 1–4.0]) during stimulation-off blocks, compared with 0.96 ± 1.23 (median 1.0 [IQR 0–1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. SignificanceThe results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.

Epilepsy Personal Assistant Device-A Mobile Platform for Brain State, Dense Behavioral and Physiology Tracking and Controlling Adaptive Stimulation.

Epilepsy is one of the most common neurological disorders, and it affects almost 1% of the population worldwide. Many people living with epilepsy continue to have seizures despite anti-epileptic medication therapy, surgical treatments, and neuromodulation therapy. The unpredictability of seizures is one of the most disabling aspects of epilepsy. Furthermore, epilepsy is associated with sleep, cognitive, and psychiatric comorbidities, which significantly impact the quality of life. Seizure predictions could potentially be used to adjust neuromodulation therapy to prevent the onset of a seizure and empower patients to avoid sensitive activities during high-risk periods. Long-term objective data is needed to provide a clearer view of brain electrical activity and an objective measure of the efficacy of therapeutic measures for optimal epilepsy care. While neuromodulation devices offer the potential for acquiring long-term data, available devices provide very little information regarding brain activity and therapy effectiveness. Also, seizure diaries kept by patients or caregivers are subjective and have been shown to be unreliable, in particular for patients with memory-impairing seizures. This paper describes the design, architecture, and development of the Mayo Epilepsy Personal Assistant Device (EPAD). The EPAD has bi-directional connectivity to the implanted investigational Medtronic Summit RC+STM device to implement intracranial EEG and physiological monitoring, processing, and control of the overall system and wearable devices streaming physiological time-series signals. In order to mitigate risk and comply with regulatory requirements, we developed a Quality Management System (QMS) to define the development process of the EPAD system, including Risk Analysis, Verification, Validation, and protocol mitigations. Extensive verification and validation testing were performed on thirteen canines and benchtop systems. The system is now under a first-in-human trial as part of the US FDA Investigational Device Exemption given in 2018 to study modulated responsive and predictive stimulation using the Mayo EPAD system and investigational Medtronic Summit RC+STM in ten patients with non-resectable dominant or bilateral mesial temporal lobe epilepsy. The EPAD system coupled with an implanted device capable of EEG telemetry represents a next-generation solution to optimizing neuromodulation therapy.

Responsive Neurostimulation of the Mesial Temporal White Matter in Bilateral Temporal Lobe Epilepsy.

Responsive neuromodulation (RNS) is a treatment option for patients with medically refractory bilateral mesial temporal lobe epilepsy (MTLE). A paucity of data exists on the feasibility and clinical outcome of hippocampal-sparing bilateral RNS depth lead placements within the parahippocampal white matter or temporal stem. To evaluate seizure reduction outcomes with at least a 1-yr follow-up in individuals with bilateral MTLE undergoing hippocampus-sparing implantation of RNS depth leads. A retrospective analysis of prospectively collected data was performed on patients at our institution with bilateral MTLE who were implanted with RNS depth leads along the longitudinal extent of bitemporal parahippocampal white matter or temporal stem. Baseline and postoperative seizure frequency, previous surgical interventions, and postimplantation electrocorticography and stimulation data were analyzed. Ten patients were included in the study (7 male, 3 female). Overall seizure frequency declined by a median 44.25% at 3.13 yr (standard deviation 3.31) postimplantation. Four patients (40%) achieved 50% responder rate at latest follow-up. Two of four patients with focal onset bilateral tonic-clonic seizures became completely seizure-free. Forty percent of patients were previously implanted with a vagus nerve stimulator, and 20% underwent a prior temporal lobectomy. All depth lead placements were confirmed as radiographically located in the parahippocampal white matter or temporal stem without hippocampus violation. There were no cases of lead malposition. Extrahippocampal or temporal stem white matter targeting during RNS surgery for bitemporal MTLE is feasible and allows for electrographic seizure detection. Larger controlled studies with longer follow-up are needed to validate these preliminary findings.

Autobiographical memory in epileptic patients after temporal lobe resection or bitemporal hippocampal sclerosis.

The human hippocampus is believed to be a crucial node in the neural network supporting autobiographical memory retrieval. Structural mesial temporal damage associated with temporal lobe epilepsy (TLE) provides an opportunity to systematically investigate and better understand the local and distal functional consequences of mesial temporal damage in the engagement of the autobiographical memory network. We examined 19 TLE patients (49.21 ± 11.55years; 12 females) with unilateral mesial TLE (MTLE; 12 with anterior temporal lobe resection: 6 right MTLE, 6 left MTLE) or bilateral mesial TLE (7 BMTLE) and 18 matched healthy subjects. We used functional MRI (fMRI) with an adapted autobiographical memory paradigm and a specific neuropsychological test (Autobiographical Memory Interview, AMI). While engaged in the fMRI autobiographical memory paradigm, all groups activated a large fronto-temporo-parietal network. However, while this network was left lateralized for healthy participants and right MTLE patients, left MTLE and patients with BMTLE also showed strong activation in right temporal and frontal regions. Moreover, BMTLE and left MTLE patients also showed significant mild deficits in episodic autobiographical memory performance measured with the AMI test. The right temporal and extra-temporal fMRI activation, along with the impairment in autobiographical memory retrieval found in left MTLE and BMTLE patients suggest that alternate brain areas-other than the hippocampus-may also support this process, possibly due to neuroplastic effects.

Hippocampal high frequency oscillations in unilateral and bilateral mesial temporal lobe epilepsy

ObjectiveThe main aim of this study was to investigate the potential differences in terms of interictal high frequency oscillations (HFOs) between both hippocampi in unilateral (U-MTLE) and bilateral mesial temporal lobe epilepsy (B-MTLE). MethodsSixteen patients with MTLE underwent bilateral hippocampal depth electrode implantation as part of epilepsy surgery evaluation. Interictal HFOs were detected automatically. The analyses entail comparisons of the rates and spatial distributions of ripples and fast ripples (FR) in hippocampi and amygdalae, with respect to the eventual finding of hippocampal sclerosis (HS). ResultsIn U-MTLE, higher ripple and FR rates were found in the hippocampi ipsilateral to the seizure onset than in the contralateral hippocampi. Non-epileptic hippocampi in U-MTLE were distinguished by significantly lower ripple rate than in the remaining analyzed hippocampi. There were not differences between the hippocampi in B-MTLE. In the hippocampi with proven HS, higher FR rates were observed in the ventral than in the dorsal parts. ConclusionsNon-epileptic hippocampi in U-MTLE demonstrated significantly lower ripple rates than those epileptic in U-MTLE and B-MTLE. SignificanceLow interictal HFO occurrence might be considered as a marker of the non-epileptic hippocampi in MTLE.

Accuracy and Efficacy for Robotic Assistance in Implanting Responsive Neurostimulation Device Electrodes in Bilateral Mesial Temporal Lobe Epilepsy.

Responsive neurostimulation (RNS) is a relatively new treatment option that has been shown to be effective for patients with medically refractory focal epilepsy when resection is not possible, especially in bilateral mesial temporal onset. Robotic devices are becoming increasingly popular for use in stereotactic procedures such as stereoelectroencephalography, but have yet to be used when implanting RNS devices. To show that these 2 forms of advanced technology were compatible and could be used effectively in patient care. We implanted RNS devices in 3 patients with bilateral mesial temporal lobe epilepsy. Each patient was placed in the prone position, and electrode trajectories were planned via the robotic navigation system via a transoccipital approach. One lead was placed along each amygdalohippocampal complex. A small craniectomy was then created in the parietal region for RNS generator implantation. Actual and expected target locations and distance were calculated for each depth. There were no complications in this group. RNS devices with bilateral leads were successfully implanted in all 3 patients, with bilateral mesial temporal lobe onset. Follow-up ranged from 3 to 6 mo, and there were no complications in this group. The median distance between the estimate and actual targets was 2.18 (range = 1.11-3.27) mm. We show that implanting RNS devices with robotic assistance is feasible with excellent precision and accuracy. The advantages of using robotic assistance include higher flexibility, accuracy, precision, and consistency.

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.

DTI-based response-driven modeling of mTLE laterality.

PurposeTo develop lateralization models for distinguishing between unilateral and bilateral mesial temporal lobe epilepsy (mTLE) and determining laterality in cases of unilateral mTLE.BackgroundmTLE is the most common form of medically refractory focal epilepsy. Many mTLE patients fail to demonstrate an unambiguous unilateral ictal onset. Intracranial EEG (icEEG) monitoring can be performed to establish whether the ictal origin is unilateral or truly bilateral with independent bitemporal ictal origin. However, because of the expense and risk of intracranial electrode placement, much research has been done to determine if the need for icEEG can be obviated with noninvasive neuroimaging methods, such as diffusion tensor imaging (DTI).MethodsFractional anisotropy (FA) was used to quantify microstructural changes reflected in the diffusivity properties of the corpus callosum, cingulum, and fornix, in a retrospective cohort of 31 patients confirmed to have unilateral (n = 24) or bilateral (n = 7) mTLE. All unilateral mTLE patients underwent resection with an Engel class I outcome. Eleven were reported to have hippocampal sclerosis on pathological analysis; nine had undergone prior icEEG. The bilateral mTLE patients had undergone icEEG demonstrating independent epileptiform activity in both right and left hemispheres. Twenty-three nonepileptic subjects were included as controls.ResultsIn cases of right mTLE, FA showed significant differences from control in all callosal subregions, in both left and right superior cingulate subregions, and in forniceal crura. Comparison of right and left mTLE cases showed significant differences in FA of callosal genu, rostral body, and splenium and the right posteroinferior and superior cingulate subregions. In cases of left mTLE, FA showed significant differences from control only in the callosal isthmus. Significant differences in FA were identified when cases of right mTLE were compared with bilateral mTLE cases in the rostral and midbody callosal subregions and isthmus. Based on 11 FA measurements in the cingulate, callosal and forniceal subregions, a response-driven lateralization model successfully differentiated all cases (n = 54) into groups of unilateral right (n = 12), unilateral left (n = 12), and bilateral mTLE (n = 7), and nonepileptic control (23).ConclusionThe proposed response-driven DTI biomarker is intended to lessen diagnostic ambiguity of laterality in cases of mTLE and help optimize selection of surgical candidates. Application of this model shows promise in reducing the need for invasive icEEG in prospective cases.

Intracranial electrographic analysis of preictal spiking and ictal onset in uni- and bitemporal epilepsy.

Ictal onset patterns in bilateral mesial temporal lobe epilepsy have not been comprehensively studied. A retrospective review of intracranial electrographic data was undertaken to establish whether it is possible to distinguish between unilateral and bilateral mesial temporal lobe epilepsy based on ictal onset patterns, including periodic preictal spiking. A total of 470 ictal onset patterns were analyzed by bitemporal extraoperative electrocorticography in 13 patients with medically intractable mesial temporal lobe epilepsy. Ictal onset patterns were categorized, by frequency, as type A (<12 Hz), type B (12-40 Hz) and type C (>40 Hz). Preictal rhythmic spiking, of at least five seconds duration, and time to contralateral propagation were also measured with each ictal event. We determined if the proportion of "ictal onset pattern frequencies" or "incidence of preictal spiking" differed between unilateral and bilateral mesial temporal lobe epilepsy. Seven patients with unilateral mesial temporal lobe epilepsy received surgery and achieved Engel class I outcomes, while the remaining six did not undergo resective surgery, due to the bilateral ictal onsets in extraoperative electrocorticography. The proportion of patients experiencing any preictal spikes was higher in unitemporal than in bitemporal cases (100% vs 50%;p=0.069). Ofthe470 ictal onset patterns analyzed (174 unitemporal and 296 bitemporal), a significant greater percentage of preictal spikes was found in unilateral cases (78% unitemporal vs 14% bitemporal; p=0.002). Low-frequency patterns were more evident in bitemporal cases (45%) than in unitemporal (10%), although the difference was not statistically significant (p=0.129). No differences were detected between the unitemporal and bitemporal groups regarding age at onset or at presentation. A greater proportion of pre ictal spiking, based on extraoperative electrocorticography, was present in unilateral, compared to bilateral, mesial temporal lobe epilepsy. Further studies are warranted to determine the causal significance of preictal spiking in mesial temporal lobe epilepsy.

Presurgical evaluation of mesial temporal lobe epilepsy with multiple advanced MR techniques at 3T

Accurate localization of the epileptogenic zone is essential for successful surgical treatment of mesial temporal lobe epilepsy (MTLE). The aim of this study was to analyze and compare the hippocampal volumetry (HV), MR spectroscopy (MRS), Dynamic susceptibility contrast (DSC) and pulsed arterial spin labeling (pASL) perfusion techniques in a large sample size of refractory MTLE patients. Forty-two patients with medically refractory MTLE who underwent preoperative evaluation and eleven normal controls were studied. Pathologic and control hippocampi were compared in terms of hippocampal volume, metabolite ratios and relative hippocampal perfusion values. By using cut-off points and asymmetry indexes, percentages of performance indicators for each technique were calculated in groups of MR (+), MR (-) and bilateral MTLE. For all techniques, a statistically significant difference was found between the pathologic and control hippocampus groups (P<0.001). Also, all of them except HV had diagnostic value in groups of MR (-) and bilateral MTLE. HV, MRS, DSC and pASL have achieved comparable performance and each of them provides important information about the lateralization of epileptogenic focus. Among those, pASL and MRS may easily be used as an adjunct to conventional MR.

The Risk-Benefit Ratio for Temporal Lobe Resection in Patients with Bilateral Mesial Temporal Lobe Epilepsy.

The Risk-Benefit Ratio for Temporal Lobe Resection in Patients with Bilateral Mesial Temporal Lobe Epilepsy.

Temporal lobe epilepsy and emotion recognition without amygdala: a case study of Urbach‐Wiethe disease and review of the literature

We describe the epilepsy features and emotion recognition abilities (recognition of basic facial emotions and recognition of emotional prosody) in a patient with Urbach-Wiethe disease with bilateral amygdala calcifications. Our data, supported by ictal video-EEG recording, indicated that our patient suffered from mesial temporal lobe epilepsy. Emotion recognition abilities were compared to those of healthy controls and those of patients with bilateral mesial temporal lobe epilepsy. Our patient showed a selective impairment of the recognition of facial expression of fear, whereas recognition of emotional prosody was preserved, in contrast to bilateral mesial temporal lobe epilepsy patients that presented with deficits in both domains. We also reviewed the literature on epilepsy in Urbach-Wiethe disease (41 patients). Our findings suggest that in Urbach-Wiethe disease, the circumscribed damage of both amygdalae results in a selective dysfunction of fearful face processing, in contrast to bilateral mesial temporal lobe epilepsy patients who present with a widespread and multimodal impairment in the judgement of emotional stimuli.

Contradictory imaging and EEG results in resection surgery of bitemporal lobe epilepsy: A case report

The present study describes the case of a 27-year-old, right-handed female with bilateral mesial temporal lobe epilepsy. Electroencephalogram (EEG) monitoring from implanted electrodes displayed two different and independent onsets on the two sides of the mesial temporal structures, which specifically included clinical generalized tonic clonic seizure (GTCS) discharges originating from the left mesial temporal lobe, as well as complex partial seizure (CPS) discharges arising from the right mesial region. However, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) showed a unilateral abnormality, as in right mesial temporal lobe sclerosis. A decision was made to resect one side of the mesial temporal lobe, in order to avoid memory function impairment, and, relying on the MRI results, the right side was selected. However, surgery did not leave the patient seizure-free. The CPSs gradually eased, while the GTCSs originating from the left side became severely aggravated. In describing this case, the drawbacks of current epileptic diagnostic methods and surgical strategies for bitemporal lobe epilepsy are discussed, and the requirement for more treatment options is emphasized.

Long-term therapeutic effects of corticoamygdalohippocampectomy for bilateral mesial temporal lobe epilepsy

Background:Some cases of paradoxical mesial temporal lobe epilepsy (MTLE) are shown to be bilateral MTLE (BMTLE) by intracranial electrodes. The treatment for BMTLE is difficult, which poses several questions. Can corticoamygdalohippocampectomy (CAH) be applied to treat BMTLE? What are the long-term therapeutic effects if CAH is performed in BMTLE patients?Methods:Four patients were shown to have BMTLE through bilateral intracranial electrode implantation. CAH was performed on the side with relatively more seizure originations. These patients were followed-up at 6 months, 1 year, 2 years and longer, in some cases, after the CAH. The postoperative seizure frequency was recorded. Preoperative and postoperative clinical memory tests and a postoperative 4-hour video electroencephalography (EEG) were conducted in the hospital at different follow-up times. The average seizure frequencies and memory quotient scores were analyzed.Results:The average seizure frequency significantly decreased by 80.8%, 83.5%, and 84.3% at different postoperative times. Although no patient was seizure free, the intensity of the seizures was reduced in all cases. The postoperative average memory quotient score was moderately decreased by 15.8%, 11.7%, and 16.6% at different postoperative times. Both the average values of the postoperative seizure frequency (5.5, 4.75, and 4.5 per month) and the average values of the postoperative memory quotient (73.7, 77.3, and 73) at different postoperative times were approximately the same.Conclusions:CAH reduced the seizure frequency and intensity in these BMTLE patients. Mild hypomnesis occurred in every case. We observed the long-term treatment effects at 6 months after the CAH and showed that the effects did not change at that time or over the next few years.

Complementary effect of surgical resection and responsive brain stimulation in the treatment of bitemporal lobe epilepsy: A case report

We report a 39-year-old man with bilateral mesial temporal lobe epilepsy. He was implanted with a responsive brain stimulator (RNS System) with two depth electrodes placed in the bimesial temporal structures. After the implantation, his seizure frequency decreased by up to 50%. Electrocorticogram recorded by the RNS device revealed the right-sided predominance of seizure onset. He underwent a right temporal lobectomy, and his seizure significantly improved. After the RNS System was restarted 107days after the temporal lobectomy, he has been seizure free for more than 1.5years. However, the implanted device continued to record residual ictal activities at the posterior aspect of the right hippocampus and delivered electrical stimuli to suppress the seizure activities. Our report indicates the importance of electrocorticographic recordings by the RNS System to modify the treatment strategy and the complementary effect of surgical resection and brain stimulation in the treatment of epilepsy.

EEG and MEG in mesial temporal lobe epilepsy: Where do the spikes really come from?

Objective There is persistent debate as to whether or not EEG and MEG recordings in patients with mesial temporal lobe epilepsy (MTLE) can detect mesial temporal interictal epileptiform discharges (spikes), and this issue is particularly relevant for source localization studies. With the aim of providing direct evidence pertinent to this debate we present detailed examples of the intracranial sources of spikes recorded with EEG and MEG in MTLE. Methods Spikes recorded in five different patients with MTLE during intracranial EEG ( n = 2), intraoperative electrocorticography (ECOG; n = 1), combined scalp-intracranial EEG ( n = 2) and combined EEG-MEG ( n = 1) were analyzed and the intracranial sources of the spike foci were matched with their corresponding extracranial EEG and/or MEG fields. EEG and MEG dipole source localization was performed on six independent spike foci identified in one representative patient with bilateral MTLE. Results Spikes with an electrical field maximal at F7/8, F9/10 ⩾ T3/4 were generated in the anterolateral temporal neocortex. The absence of coincident spiking at mesial locations indicated that these were not propagated from or to the hippocampus. Spikes with an electrical field maximal at T3/4 ⩾ T9/10 were generated in the lateral temporal neocortex and likewise did not involve the hippocampus. Individual spikes generated in the mesiobasal temporal neocortex, including the fusiform gyrus, were difficult to detect with EEG (low amplitude diphasic waves most apparent after spike averaging at T3/4, T9/10 ⩾ T5/6, P9/10) and only slightly more identifiable with MEG. Spikes generated within and confined to the mesial temporal structures, as confirmed by intracranial recordings, could not be detected with EEG or MEG. Notably, such spikes could not be detected even at intracranial recording sites on the lateral surface of the temporal lobe. Conclusions We present detailed evidence in a small case series showing that typical anterior temporal spikes recorded with EEG and MEG in MTLE arose from the anterolateral temporal neocortex and were neither propagated from nor to the hippocampus. Mid temporal EEG spikes were localized to the lateral temporal neocortex. Intracranially detected mesial temporal spikes were not detected with EEG or MEG. Significance The spikes recorded with EEG and MEG in MTLE are localized to neocortical foci, and not to the mesial temporal structures. Current noninvasive EEG and MEG source localization studies cannot accurately identify true mesial temporal spikes.