Interneuron transplantation: a prospective surgical therapy for medically refractory epilepsy.

Excitatory-inhibitory imbalance is central to epilepsy pathophysiology. Current surgical therapies for epilepsy, such as brain resection, laser ablation, and neurostimulation, target epileptic networks on macroscopic scales, without directly correcting the circuit-level aberrations responsible for seizures. The transplantation of inhibitory cortical interneurons represents a novel neurobiological method for modifying recipient neural circuits in a physiologically corrective manner. Transplanted immature interneurons have been found to disperse in the recipient brain parenchyma, where they develop elaborate structural morphologies, express histochemical markers of mature interneurons, and form functional inhibitory synapses onto recipient neurons. Transplanted interneurons also augment synaptic inhibition and alter recipient neural network synchrony, two physiological processes disrupted in various epilepsies. In rodent models of epilepsy, interneuron transplantation corrects recipient seizure phenotypes and associated behavioral abnormalities. As such, interneuron transplantation may represent a novel neurobiological approach to the surgical treatment of human epilepsy. Here, the authors describe the preclinical basis for applying interneuron transplantation to human epilepsy, discuss its potential clinical applications, and consider the translational hurdles to its development as a surgical therapy.

Temporal lobe structural evaluation after transsylvian selective amygdalohippocampectomy.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adolescents and adults, and in 65% of cases, it is related to hippocampal sclerosis (HS). Selective surgical approaches to the treatment of MTLE have as their main goal resection of the amygdala and hippocampus with minimal damage to the neocortex, temporal stem, and optic radiations (ORs). The object of this study was to evaluate late postoperative imaging findings on the temporal lobe from a structural point of view. METHODS: The authors conducted a retrospective evaluation of all patients with refractory MTLE who had undergone transsylvian selective amygdalohippocampectomy (SAH) in the period from 2002 to 2015. A surgical group was compared to a control group (i.e., adults with refractory MTLE with an indication for surgical treatment of epilepsy but who did not undergo the surgical procedure). The inferior frontooccipital fasciculus (IFOF), uncinate fasciculus (UF), and ORs were evaluated on diffusion tensor imaging analysis. The temporal pole neocortex was evaluated using T2 relaxometry. RESULTS: For the IFOF and UF, there was a decrease in anisotropy, voxels, and fibers in the surgical group compared with those in the control group (p < 0.001). An increase in relaxometry time in the surgical group compared to that in the control group (p < 0.001) was documented, suggesting gliosis and neuronal loss in the temporal pole. CONCLUSIONS: SAH techniques do not seem to totally preserve the temporal stem or even spare the neocortex of the temporal pole. Therefore, although the transsylvian approaches have been considered to be anatomically selective, there is evidence that the temporal pole neocortex suffers structural damage and potentially functional damage with these approaches.

Seizure freedom after laser amygdalohippocampotomy guided by bilateral responsive neurostimulation in pediatric epilepsy: illustrative case.

BACKGROUND: For patients with difficult-to-lateralize temporal lobe epilepsy, the use of chronic recordings as a diagnostic tool to inform subsequent surgical therapy is an emerging paradigm that has been reported in adults but not in children. OBSERVATIONS: The authors reported the case of a 15-year-old girl with pharmacoresistant temporal lobe epilepsy who was found to have bitemporal epilepsy during a stereoelectroencephalography (sEEG) admission. She underwent placement of a responsive neurostimulator system with bilateral hippocampal depth electrodes. However, over many months, her responsive neurostimulation (RNS) recordings revealed that her typical, chronic seizures were right-sided only. This finding led to a subsequent right-sided laser amygdalohippocampotomy, resulting in seizure freedom. LESSONS: In this case, RNS chronic recording provided real-world data that enabled more precise seizure localization than inpatient sEEG data, informing surgical decision-making that led to seizure freedom. The use of RNS chronic recordings as a diagnostic adjunct to seizure localization procedures and laser ablation therapies in children is an area with potential for future study.

Laser ablative treatment of musicogenic epilepsy arising from dominant mesial temporal lobe: illustrative case.

BACKGROUND: Musicogenic epilepsy (ME) is a rare reflex epilepsy in which seizures are triggered by musical stimuli. Prior descriptions of ME have suggested localization to the nondominant temporal lobe, primarily in neocortex. Although resection has been described as a treatment for ME, other surgical modalities, such as laser ablation, may effectively disrupt seizure networks in ME while incurring comparatively lower risks of morbidity. The authors described the use of laser ablation to treat ME arising from the dominant mesial temporal structures. OBSERVATIONS: A 37-year-old woman with a 15-year history of drug-resistant ME was referred for surgical evaluation. Her seizures were triggered by specific musical content and involved behavioral arrest, repetitive swallowing motions, and word incomprehension. Diagnostic studies, including magnetic resonance imaging, single-photon emission computed tomography, magnetoencephalography, Wada testing, and stereoelectroencephalography, indicated seizure onset in the left (dominant) mesial temporal lobe. Laser interstitial thermal therapy was used to ablate the left mesial seizure onset zone. The patient was discharged on postoperative day two. At 18-month follow-up, she was seizure-free with no posttreatment neurological deficits. LESSONS: Laser ablation can be an effective treatment option for well-localized forms of ME, particularly when seizures originate from the dominant mesial temporal lobe.

Resective, Ablative and Radiosurgical Interventions for Drug Resistant Mesial Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis of Outcomes.

Objectives: One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected. We compare published outcomes following open surgical techniques, radiosurgery (SRS), laser interstitial thermal therapy (LITT) and radiofrequency ablation (RF-TC). Methods: PRISMA systematic review was performed through structured searches of PubMed, Embase and Cochrane databases. Inclusion criteria encompassed studies of MTLE reporting seizure-free outcomes in ≥10 patients with ≥12 months follow-up. Due to variability in open surgical approaches, only comparative studies were included to minimize the risk of bias. Random effects meta-analysis was performed to calculate effects sizes and a pooled estimate of the probability of seizure freedom per person-year. A mixed effects linear regression model was performed to compare effect sizes between interventions. Results: From 1,801 screened articles, 41 articles were included in the quantitative analysis. Open surgery included anterior temporal lobe resection as well as transcortical and trans-sylvian selective amygdalohippocampectomy. The pooled seizure-free rate per person-year was 0.72 (95% CI 0.66-0.79) with trans-sylvian selective amygdalohippocampectomy, 0.59 (95% CI 0.53-0.65) with LITT, 0.70 (95% CI 0.64-0.77) with anterior temporal lobe resection, 0.60 (95% CI 0.49-0.73) with transcortical selective amygdalohippocampectomy, 0.38 (95% CI 0.14-1.00) with RF-TC and 0.50 (95% CI 0.34-0.73) with SRS. Follow up duration and study sizes were limited with LITT and RF-TC. A mixed-effects linear regression model suggests significant differences between interventions, with LITT, ATLR and SAH demonstrating the largest effects estimates and RF-TC the lowest. Conclusions: Overall, novel "minimally invasive" approaches are still comparatively less efficacious than open surgery. LITT shows promising seizure effectiveness, however follow-up durations are shorter for minimally invasive approaches so the durability of the outcomes cannot yet be assessed. Secondary outcome measures such as Neurological complications, neuropsychological outcome and interventional morbidity are poorly reported but are important considerations when deciding on first-line treatments.

Characterization of postsurgical functional connectivity changes in temporal lobe epilepsy.

OBJECTIVE: Seizure outcome after mesial temporal lobe epilepsy (mTLE) surgery is complex and diverse, even across patients with homogeneous presurgical clinical profiles. The authors hypothesized that this is due in part to variations in network connectivity across the brain before and after surgery. Although presurgical network connectivity has been previously characterized in these patients, the objective of this study was to characterize presurgical to postsurgical functional network connectivity changes across the brain after mTLE surgery. METHODS: Twenty patients with drug-refractory unilateral mTLE (5 left side, 10 female, age 39.3 ± 13.5 years) who underwent either selective amygdalohippocampectomy (n = 13) or temporal lobectomy (n = 7) were included in the study. Presurgical and postsurgical (36.6 ± 14.3 months after surgery) functional connectivity (FC) was measured with 3-T MRI and compared with findings in age-matched healthy controls (n = 44, 21 female, age 39.3 ± 14.3 years). Postsurgical connectivity changes were then related to seizure outcome, type of surgery, and presurgical disease parameters. RESULTS: The results demonstrated significant decreases of FC from control group values across the brain after surgery that were not present before surgery, including many contralateral hippocampal connections distal to the surgical site. Postsurgical impairment of contralateral precuneus to ipsilateral occipital connectivity was associated with seizure recurrence. Presurgical impairment of the contralateral precuneus to contralateral temporal lobe connectivity was associated with those who underwent selective amygdalohippocampectomy compared to those who had temporal lobectomy. Finally, changes in thalamic connectivity after surgery were linearly related to duration of epilepsy and frequency of consciousness-impairing seizures prior to surgery. CONCLUSIONS: The widespread contralateral hippocampal FC changes after surgery may be a reflection of an ongoing epileptogenic progression that has been altered by the surgery, rather than a direct result of the surgery itself. This network evolution may contribute to long-term seizure outcome. Therefore, the combination of presurgical network mapping with the understanding of the dynamic effects of surgery on the networks may ultimately be used to create predictors of the likelihood of long-term seizure recurrence in individual patients after mTLE surgery.

Magnetic resonance-guided focused ultrasound for ablation of mesial temporal epilepsy circuits: modeling and theoretical feasibility of a novel noninvasive approach.

OBJECTIVE: The authors tested the feasibility of magnetic resonance-guided focused ultrasound (MRgFUS) ablation of mesial temporal lobe epilepsy (MTLE) seizure circuits. Up to one-third of patients with mesial temporal sclerosis (MTS) suffer from medically refractory epilepsy requiring surgery. Because current options such as open resection, laser ablation, and Gamma Knife radiosurgery pose potential risks, such as infection, hemorrhage, and ionizing radiation, and because they often produce visual or neuropsychological deficits, the authors developed a noninvasive MRgFUS ablation strategy for mesial temporal disconnection to mitigate these risks. METHODS: The authors retrospectively reviewed 3-T MRI scans obtained with diffusion tensor imaging (DTI). The study group included 10 patients with essential tremor (ET) who underwent pretreatment CT and MRI prior to MRgFUS, and 2 patients with MTS who underwent MRI. Fiber tracking of the fornix-fimbria pathway and inferior optic radiations was performed, ablation sites mimicking targets of open posterior hippocampal disconnection were modeled, and theoretical MRgFUS surgical plans were devised. Distances between the targets and optic radiations were measured, helmet angulations were prescribed, and the numbers of available MRgFUS array elements were calculated. RESULTS: Tractograms of fornix-fimbria and optic radiations were generated in all ET and MTS patients successfully. Of the 10 patients with both the CT and MRI data necessary for the analysis, 8 patients had adequate elements available to target the ablation site. A margin (mean 8.5 mm, range 6.5-9.8 mm) of separation was maintained between the target lesion and optic radiations. CONCLUSIONS: MRgFUS offers a noninvasive option for seizure tract disruption. DTI identifies fornix-fimbria and optic radiations to localize optimal ablation targets and critical surrounding structures, minimizing risk of postoperative visual field deficits. This theoretical modeling study provides the necessary groundwork for future clinical trials to apply this novel neurosurgical technique to patients with refractory MTLE and surgical contraindications, multiple prior surgeries, or other factors favoring noninvasive treatment.

Stereotactic laser ablation for nonlesional cingulate epilepsy: case report.

Stereotactic laser ablation (SLA) is being increasingly used to treat refractory focal epilepsy, especially mesial temporal lobe epilepsy. However, emerging evidence suggests it can be used for extratemporal lobe epilepsy as well.The authors report the case of a 17-year-old male who presented with refractory nocturnal seizures characterized by bilateral arms stiffening or rhythmic jerking lasting several seconds. Semiology suggested an epileptogenic zone close to one of the supplementary sensory motor areas. Electroencephalography showed seizures arising from the central region without consistent lateralization. Brain imaging showed no abnormality. An invasive evaluation using bilateral stereoelectroencephalography (SEEG) was utilized in 2 steps, first to establish the laterality of seizures, and second to further cover the mesial cingulate region of the right hemisphere. Seizures arose from the middle portion of the right cingulate gyrus. Extraoperative electrical mapping revealed that the seizure onset zone was adjacent to eloquent motor areas. SLA targeting the right midcingulate gyrus was performed. The patient has remained seizure free since immediately after the procedure with no postoperative deficits (follow-up of 17 months).This case highlights the utility of SEEG in evaluating difficult-to-localize, focal epilepsy. It also demonstrates that the use of SLA can be extended to nonlesional, extratemporal epilepsies.

Efficacy of limited hippocampal radiofrequency thermocoagulation for mesial temporal lobe epilepsy.

OBJECTIVE: Radiofrequency thermocoagulation (RFTC), which has been developed for drug-resistant epilepsy patients, involves less brain tissue loss due to surgery, fewer surgical adverse effects, and generally good seizure control. This study demonstrates the effectiveness of RFTC performed at limited hippocampal locations. METHODS: Daily seizure diaries were prospectively maintained for at least 6 months by 9 patients (ages 30-59 years) with drug-resistant mesial temporal lobe epilepsy (MTLE) before treatment with RFTC. The limited target for stereotactic RFTC was chosen based on intraoperative electroencephalography (EEG) recording and was initially tested with a Radionics electrode at a low temperature, 45°C, for 60 seconds. The therapeutic RFTC heating parameters were 78°C-80°C for 90 seconds. All patients who received the RFTC treatment underwent both MRI and EEG recording immediately postoperatively and at the 3-month follow-up. Monthly outpatient clinic visits were arranged over 6 months to document seizure frequency and severity to clarify the changes noted in imaging studies and EEG patterns. RESULTS: Two patients were excluded from our analysis because one had undergone multiple seizure surgeries and the other had a poor recording of seizure frequency, before the RFTC surgery. Five and two patients underwent left-sided and right-sided RFTC, respectively. None of the patients had generalized tonic-clonic attacks postoperatively, and no adverse effects or complications occurred. According to MRI data, the effect of coagulation was limited to less than 1.0 cm in diameter and perifocal edema was also in limited range. The seizure frequency within 6 months decreased postoperatively with a mean reduction in seizures of 78% (range 36%-100%). Only two patients had a temporary increase in seizure frequency within 2 weeks of the surgery, and over 50% of all patients showed a decrease in average seizure frequency. CONCLUSIONS: The study results confirm that limited RFTC provides a more effective surgery with similar seizure control but fewer complications than resective surgery for drug-resistant MTLE patients.

Mesial temporal lobe epilepsy: long-term seizure outcome of patients primarily treated with transsylvian selective amygdalohippocampectomy.

OBJECTIVE The aim of this study was to present long-term seizure outcome data in a consecutive series of patients with refractory mesial temporal lobe epilepsy primarily treated with transsylvian selective amygdalohippocampectomy (SAHE). METHODS The authors retrospectively analyzed prospectively collected data for all patients who had undergone resective surgery for medically refractory epilepsy at their institution between July 1994 and December 2014. Seizure outcome was assessed according to the International League Against Epilepsy (ILAE) and the Engel classifications. RESULTS The authors performed an SAHE in 158 patients (78 males, 80 females; 73 right side, 85 left side) with a mean age of 37.1 ± 10.0 years at surgery. Four patients lost to follow-up and 1 patient who committed suicide were excluded from analysis. The mean follow-up period was 9.7 years. At the last available follow-up (or before reoperation), 68 patients (44.4%) had achieved an outcome classified as ILAE Class 1a, 46 patients (30.1%) Class 1, 6 patients (3.9%) Class 2, 16 patients (10.4%) Class 3, 15 patients (9.8%) Class 4, and 2 patients (1.3%) Class 5. These outcomes correspond to Engel Class I in 78.4% of the patients, Engel Class II in 10.5%, Engel Class III in 8.5%, and Engel Class IV in 2.0%. Eleven patients underwent a second surgery (anterior temporal lobectomy) after a mean of 4.4 years from the SAHE (left side in 6 patients, right side in 5). Eight (72.7%) of these 11 patients achieved seizure freedom. The overall ILEA seizure outcome since (re)operation after a mean follow-up of 10.0 years was Class 1a in 72 patients (47.0%), Class 1 in 50 patients (32.6%), Class 2 in 7 patients (4.6%), Class 3 in 15 patients (9.8%), Class 4 in 8 patients (5.2%), and Class 5 in 1 patient (0.6%). These outcomes correspond to an Engel Class I outcome in 84.3% of the patients. CONCLUSIONS A satisfactory long-term seizure outcome following transsylvian SAHE was demonstrated in a selected group of patients with refractory temporal lobe epilepsy.

Indications, technique, and safety profile of insular stereoelectroencephalography electrode implantation in medically intractable epilepsy.

OBJECTIVE Insular epilepsy is relatively rare; however, exploring the insular cortex when preoperative workup raises the suspicion of insular epilepsy is of paramount importance for accurate localization of the epileptogenic zone and achievement of seizure freedom. The authors review their clinical experience with stereoelectroencephalography (SEEG) electrode implantation in patients with medically intractable epilepsy and suspected insular involvement. METHODS A total of 198 consecutive cases in which patients underwent SEEG implantation with a total of 1556 electrodes between June 2009 and April 2013 were reviewed. The authors identified patients with suspected insular involvement based on seizure semiology, scalp EEG data, and preoperative imaging (MRI, PET, and SPECT or magnetoencephalography [MEG]). Patients with at least 1 insular electrode based on the postoperative 3D reconstruction of CT fused with the preoperative MRI were included. RESULTS One hundred thirty-five patients with suspected insular epilepsy underwent insular implantation of a total of 303 electrodes (1-6 insular electrodes per patient) with a total of 562 contacts. Two hundred sixty-eight electrodes (88.5%) were implanted orthogonally through the frontoparietal or temporal operculum (420 contacts). Thirty-five electrodes (11.5%) were implanted by means of an oblique trajectory either through a frontal or a parietal entry point (142 contacts). Nineteen patients (14.07%) had insular electrodes placed bilaterally. Twenty-three patients (17.04% of the insular implantation group and 11.6% of the whole SEEG cohort) were confirmed by SEEG to have ictal onset zones in the insula. None of the patients experienced any intracerebral hemorrhage related to the insular electrodes. After insular resection, 5 patients (33.3%) had Engel Class I outcomes, 6 patients (40%) had Engel Class II, 3 patients (20%) had Engel Class III, and 1 patient (6.66%) had Engel Class IV. CONCLUSIONS Insula exploration with stereotactically placed depth electrodes is a safe technique. Orthogonal electrodes are implanted when the hypothesis suggests opercular involvement; however, oblique electrodes allow a higher insular sampling rate.

Role of the temporal pole in temporal lobe epilepsy seizure networks: an intracranial electrode investigation.

OBJECTIVE A convergence of clinical research suggests that the temporal pole (TP) plays an important and potentially underappreciated role in the genesis and propagation of seizures in temporal lobe epilepsy (TLE). Understanding its role is becoming increasingly important because selective resections for medically intractable TLE spare temporopolar cortex (TPC). The purpose of this study was to characterize the role of the TPC in TLE after using dense electrocorticography (ECoG) recordings in patients undergoing invasive monitoring for medically intractable TLE. METHODS Chronic ECoG recordings were obtained in 10 consecutive patients by using an array customized to provide dense coverage of the TP as part of invasive monitoring to localize the epileptogenic zone. All patients would eventually undergo cortico-amygdalohippocampectomy. A retrospective review of the patient clinical records including ECoG recordings, neuroimaging studies, neuropathology reports, and clinical outcomes was performed. RESULTS In 7 patients (70%), the TP was involved at seizure onset; in 7 patients (70%), there were interictal discharges from the TP; and in 1 case, there was early spread to the TP. Seizure onset in the TP did not necessarily correlate with preoperative neuroimaging abnormalities of the TP. CONCLUSIONS These data demonstrate that TPC commonly plays a crucial role in temporal lobe seizure networks. Seizure onset from the TP would not have been predicted based on available neuroimaging data or interictal discharges. These findings illustrate the importance of thoroughly considering the role of the TP prior to resective surgery for TLE, particularly when selective mesial resection is being considered.

Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study.

OBJECTIVE In appropriate candidates, the treatment of medication-refractory mesial temporal lobe epilepsy (MTLE) is primarily surgical. Traditional anterior temporal lobectomy yields seizure-free rates of 60%-70% and possibly higher. The field of magnetic resonance-guided focused ultrasound (MRgFUS) is an evolving field in neurosurgery. There is potential to treat MTLE with MRgFUS; however, it has appeared that the temporal lobe structures were beyond the existing treatment envelope of currently available clinical systems. The purpose of this study was to determine whether lesional temperatures can be achieved in the target tissue and to assess potential safety concerns. METHODS Cadaveric skulls with tissue-mimicking gels were used as phantom targets. An ablative volume was then mapped out for a "virtual temporal lobectomy." These data were then used to create a target volume on the InSightec ExAblate Neuro system. The target was the amygdala, uncus, anterior 20 mm of hippocampus, and adjacent parahippocampal gyrus. This volume was approximately 5cm3. Thermocouples were placed on critical skull base structures to monitor skull base heating. RESULTS Adequate focusing of the ultrasound energy was possible in the temporal lobe structures. Using clinically relevant ultrasound parameters (power 900 W, duration 10 sec, frequency 650 kHz), ablative temperatures were not achieved (maximum temperature 46.1°C). Increasing sonication duration to 30 sec demonstrated lesional temperatures in the mesial temporal lobe structures of interest (up to 60.5°C). Heating of the skull base of up to 24.7°C occurred with 30-sec sonications. CONCLUSIONS MRgFUS thermal ablation of the mesial temporal lobe structures relevant in temporal lobe epilepsy is feasible in a laboratory model. Longer sonications were required to achieve temperatures that would create permanent lesions in brain tissue. Heating of the skull base occurred with longer sonications. Blocking algorithms would be required to restrict ultrasound beams causing skull base heating. In the future, MRgFUS may present a minimally invasive, non-ionizing treatment of MTLE.

Neuropsychological outcomes of subtemporal selective amygdalohippocampectomy via a small craniotomy.

OBJECT The objectives of this study were to describe a novel minimal-access subtemporal approach for selective resection of the amygdala and hippocampus in patients with medically refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis, and to analyze the related outcomes. METHODS The authors analyzed data from all cases involving patients with unilateral MTLE due to hippocampal sclerosis who were treated with selective amygdalohippocampectomy via the posterior subtemporal approach through a relatively small craniotomy, without a neuronavigation system, at their institution during the period from September 2010 to September 2012. Data were obtained on baseline characteristics, preoperative evaluations of unilateral mesial temporal sclerosis, surgical complications, and Engel class seizure outcomes. All patients underwent memory testing, IQ testing, and language testing. RESULTS The mean duration of follow-up was 33.6 months (range 24-48 months). There were no deaths and no cases of significant postoperative morbidity. One patient had a mild complication. At 2-year follow-up, 19 patients were seizure free (Engel Class I outcome). Verbal memory scores obtained at 3 months and at 2 years after surgery were significantly lower than preoperative scores for patients who underwent surgery on the left side of the brain (p < 0.05). Pictorial memory scores were higher following surgery compared with before surgery regardless of whether patients underwent left- or right-sided brain surgery. There was also improvement in performance IQ and total IQ following surgery in both groups. For patients who underwent right-sided brain surgery, verbal comprehension and semantic fluency testing scores were significantly higher at both 3 months and 2 years after surgery than before surgery. For patients who underwent left-sided brain surgery, scores on all language tests were significantly lower at 3 months after surgery than before surgery. Verbal comprehension testing scores returned to the preoperative level at 2 years after surgery. CONCLUSIONS The posterior subtemporal approach through a relatively small craniotomy allows adequate exposure and safe resection of mesial temporal structures and effectively reduces medically intractable MTLE. It preserves IQ but may have a detrimental effect on verbal memory and language ability.

Stereoelectroencephalography-guided radiofrequency thermocoagulation in the epileptogenic zone: a retrospective study on 89 cases.

OBJECT: Radiofrequency thermocoagulation (RF-TC) of presumed epileptogenic lesions and/or structures has gained new popularity as a treatment option for drug-resistant focal epilepsy, mainly in patients with mesial temporal lobe epilepsy. The role of this minimally invasive procedure in more complex cases of drug-resistant epilepsy, which may require intracranial electroencephalographic evaluation, has not been fully assessed. This retrospective study reports on a case series of patients with particularly complex focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation with stereotactically implanted multicontact intracerebral electrodes for the detailed identification of the epileptogenic zone (EZ) and who received RF-TC in their supposed EZ (according to SEEG findings). METHODS: Eighty-nine patients (49 male and 40 female; age range 2-49 years) who underwent SEEG evaluation and subsequent RF-TC of the presumed EZ at the authors' institution between January 2008 and December 2013 were selected. Brain MRI revealed structural abnormalities in 43 cases and no lesions in 46 cases. After SEEG, 67 patients were judged suitable for resective surgery (Group 1), whereas surgery was excluded for 22 patients (Group 2). Thermocoagulation was performed in each of these patients by using the previously implanted multicontact recording electrodes and delivering RF-generated currents to adjacent electrode contacts. RESULTS: The mean number of TC sites per patient was 10.6 ± 7.2 (range 1-33). Sustained seizure freedom occurred after TC in 16 patients (18.0%) (13 in Group 1 and 3 in Group 2). A sustained worthwhile improvement was reported by 9 additional patients (10.1%) (3 in Group 1 and 6 in Group 2). As a whole, 25 patients (28.1%) exhibited a persistent significant improvement in their seizures. More favorable results were observed in patients with nodular heterotopy (p = 0.0001389), those with a lesion found on MRI (not significant), and those with hippocampal sclerosis (not significant). Other variables significantly correlated to seizure freedom were the patient's age (p = 0.02885) and number of intralesional TC sites (p = 0.0271). The patients in Group 1 who did not benefit at all (21 patients) or who experienced only a transient benefit (30 patients) from TC underwent microsurgical resection of their EZ. Thermocoagulation was followed by severe permanent neurological deficits in 2 patients (an unexpected complex neuropsychological syndrome in one patient and an expected and anticipated permanent motor deficit in the other). CONCLUSIONS: This study provides evidence that SEEG-guided TC in the EZ may be a treatment option for particularly complex drug-resistant focal epilepsy that requires invasive evaluation. A small subset of patients who achieve seizure freedom or worthwhile improvement may avoid open surgery or take advantage of an otherwise unexpected treatment if resection is not an option. Patients with epileptogenic nodular heterotopy are probably ideal candidates for this treatment.

Radiosurgery for temporal lobe arteriovenous malformations: effect of temporal location on seizure outcomes.

OBJECT: The temporal lobe is particularly susceptible to epileptogenesis. However, the routine use of anticonvulsant therapy is not implemented in temporal lobe AVM patients without seizures at presentation. The goals of this case-control study were to determine the radiosurgical outcomes for temporal lobe AVMs and to define the effect of temporal lobe location on postradiosurgery AVM seizure outcomes. METHODS: From a database of approximately 1400 patients, the authors generated a case cohort from patients with temporal lobe AVMs with at least 2 years follow-up or obliteration. A control cohort with similar baseline AVM characteristics was generated, blinded to outcome, from patients with non-temporal, cortical AVMs. They evaluated the rates and predictors of seizure freedom or decreased seizure frequency in patients with seizures or de novo seizures in those without seizures. RESULTS: A total of 175 temporal lobe AVMs were identified based on the inclusion criteria. Seizure was the presenting symptom in 38% of patients. The median AVM volume was 3.3 cm3, and the Spetzler-Martin grade was III or higher in 39% of cases. The median radiosurgical prescription dose was 22 Gy. At a median clinical follow-up of 73 months, the rates of seizure control and de novo seizures were 62% and 2%, respectively. Prior embolization (p = 0.023) and lower radiosurgical dose (p = 0.027) were significant predictors of seizure control. Neither temporal lobe location (p = 0.187) nor obliteration (p = 0.522) affected seizure outcomes. The cumulative obliteration rate was 63%, which was significantly higher in patients without seizures at presentation (p = 0.046). The rates of symptomatic and permanent radiation-induced changes were 3% and 1%, respectively. The annual risk of postradiosurgery hemorrhage was 1.3%. CONCLUSIONS: Radiosurgery is an effective treatment for temporal lobe AVMs. Furthermore, radiosurgery is protective against seizure progression in patients with temporal lobe AVM-associated seizures. Temporal lobe location does not affect radiosurgery-induced seizure control. The low risk of new-onset seizures in patients with temporal or extratemporal AVMs does not seem to warrant prophylactic use of anticonvulsants.

Gamma Knife radiosurgery for recurrent or residual seizures after anterior temporal lobectomy in mesial temporal lobe epilepsy patients with hippocampal sclerosis: long-term follow-up results of more than 4 years.

OBJECT: Gamma Knife radiosurgery (GKRS) has proven efficacy in the treatment of drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and is comparable to conventional resective surgery. It may be effective as an alternative treatment to reoperation after failed temporal lobe surgery in patients with MTLE-HS. The purpose of this study was to investigate the efficacy of GKRS in patients with unilateral MTLE-HS who did not achieve seizure control or had recurrent seizures after anterior temporal lobectomy (ATL). METHODS: Twelve patients (8 males; mean age 35.50 ± 9.90 years) with MTLE-HS who underwent GKRS after failed ATL (Engel Classes III-IV) were included. GKRS targets included the remnant tissue or adjacent regions of the previously performed ATL with a marginal dose of 24-25 Gy at the 50% isodose line in all patients. Final seizure outcome was assessed using Engel's modified criteria during the final 2 years preceding data analysis. A comparison between signal changes on follow-up MRI and clinical outcome was performed. RESULTS: All patients were followed up for at least 4 years with a mean duration of 6.18 ± 1.77 years (range 4-8.8 years) after GKRS. At the final assessment, 6 of 12 patients were classified as seizure free (Engel Class Ia, n = 3; Ic, n = 2; and Id, n = 1) and 6 patients were classified as not seizure free (Engel Class II, n = 1; III, n = 2; and IV, n = 3). Neither initial nor late MRI signal changes after GKRS statistically correlated with surgical outcome. Clinical seizure outcome did not differ significantly with initial or late MRI changes after GKRS. CONCLUSIONS: GKRS can be considered an alternative option when the patients with MTLE-HS who had recurrent or residual seizures after ATL refuse a second operation.

Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies.

Minimally invasive surgical techniques for the treatment of medically intractable epilepsy, which have been developed by neurosurgeons and epileptologists almost simultaneously with standard open epilepsy surgery, provide benefits in the traditional realms of safety and efficacy and the more recently appreciated realms of patient acceptance and costs. In this review, the authors discuss the shortcomings of the gold standard of open epilepsy surgery and summarize the techniques developed to provide minimally invasive alternatives. These minimally invasive techniques include stereotactic radiosurgery using the Gamma Knife, stereotactic radiofrequency thermocoagulation, laser-induced thermal therapy, and MRI-guided focused ultrasound ablation.