Measurable transitions during seizures in intracranial EEG: A stereoelectroencephalography and SPECT study.

OBJECTIVE: Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. METHODS: We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. RESULTS: Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. CONCLUSIONS: Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. SIGNIFICANCE: Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states.

Effective connectivity relates seizure outcome to electrode placement in responsive neurostimulation.

Responsive neurostimulation is a closed-loop neuromodulation therapy for drug resistant focal epilepsy. Responsive neurostimulation electrodes are placed near ictal onset zones so as to enable detection of epileptiform activity and deliver electrical stimulation. There is no standard approach for determining the optimal placement of responsive neurostimulation electrodes. Clinicians make this determination based on presurgical tests, such as MRI, EEG, magnetoencephalography, ictal single-photon emission computed tomography and intracranial EEG. Currently functional connectivity measures are not being used in determining the placement of responsive neurostimulation electrodes. Cortico-cortical evoked potentials are a measure of effective functional connectivity. Cortico-cortical evoked potentials are generated by direct single-pulse electrical stimulation and can be used to investigate cortico-cortical connections in vivo. We hypothesized that the presence of high amplitude cortico-cortical evoked potentials, recorded during intracranial EEG monitoring, near the eventual responsive neurostimulation contact sites is predictive of better outcomes from its therapy. We retrospectively reviewed 12 patients in whom cortico-cortical evoked potentials were obtained during stereoelectroencephalography evaluation and subsequently underwent responsive neurostimulation therapy. We studied the relationship between cortico-cortical evoked potentials, the eventual responsive neurostimulation electrode locations and seizure reduction. Directional connectivity indicated by cortico-cortical evoked potentials can categorize stereoelectroencephalography electrodes as either receiver nodes/in-degree (an area of greater inward connectivity) or projection nodes/out-degree (greater outward connectivity). The follow-up period for seizure reduction ranged from 1.3-4.8 years (median 2.7) after responsive neurostimulation therapy started. Stereoelectroencephalography electrodes closest to the eventual responsive neurostimulation contact site tended to show larger in-degree cortico-cortical evoked potentials, especially for the early latency cortico-cortical evoked potentials period (10-60 ms period) in six out of 12 patients. Stereoelectroencephalography electrodes closest to the responsive neurostimulation contacts (≤5 mm) also had greater significant out-degree in the early cortico-cortical evoked potentials latency period than those further away (≥10 mm) (P < 0.05). Additionally, significant correlation was noted between in-degree cortico-cortical evoked potentials and greater seizure reduction with responsive neurostimulation therapy at its most effective period (P < 0.05). These findings suggest that functional connectivity determined by cortico-cortical evoked potentials may provide additional information that could help guide the optimal placement of responsive neurostimulation electrodes.

Novel noninvasive identification of patient-specific epileptic networks in focal epilepsies: Linking single-photon emission computed tomography perfusion during seizures with resting-state magnetoencephalography dynamics.

Single-photon emission computed tomography (SPECT) during seizures and magnetoencephalography (MEG) during the interictal state are noninvasive modalities employed in the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy (DRFE). The present study aims to investigate whether there exists a preferentially high MEG functional connectivity (FC) among those regions of the brain that exhibit hyperperfusion or hypoperfusion during seizures. We studied MEG and SPECT data in 30 consecutive DRFE patients who had resective epilepsy surgery. We parcellated each ictal perfusion map into 200 regions of interest (ROIs) and generated ROI time series using source modeling of MEG data. FC between ROIs was quantified using coherence and phase-locking value. We defined a generalized linear model to relate the connectivity of each ROI, ictal perfusion z score, and distance between ROIs. We compared the coefficients relating perfusion z score to FC of each ROI and estimated the connectivity within and between resected and unresected ROIs. We found that perfusion z scores were strongly correlated with the FC of hyper-, and separately, hypoperfused ROIs across patients. High interictal connectivity was observed between hyperperfused brain regions inside and outside the resected area. High connectivity was also observed between regions of ictal hypoperfusion. Importantly, the ictally hypoperfused regions had a low interictal connectivity to regions that became hyperperfused during seizures. We conclude that brain regions exhibiting hyperperfusion during seizures highlight a preferentially connected interictal network, whereas regions of ictal hypoperfusion highlight a separate, discrete and interconnected, interictal network.

Clinical significance of ictal magnetoencephalography in patients undergoing epilepsy surgery.

OBJECTIVE: The significance of ictal magnetoencephalography (MEG) is not well appreciated. We evaluated the relationships between ictal MEG, MRI, intracranial electroencephalography (ICEEG), surgery and postoperative seizure outcome. METHODS: A total of 45 patients (46 cases) with ictal MEG who underwent epilepsy surgery was included. We examined the localization of each modality, surgical resection area and seizure freedom after surgery. RESULTS: Twenty-one (45.7%) out of 46 cases were seizure-free at more than 6 months follow-up. Median duration of postoperative follow-up was 16.5 months. The patients in whom ictal, interictal single equivalent current dipole (SECD) and MRI lesion localization were completely included in the resection had a higher chance of being seizure-free significantly (p < 0.05). Concordance between ictal and interictal SECD localizations was significantly associated with seizure-freedom. Concordance between MRI lesion and ictal SECD, concordance between ictal ICEEG and ictal and interictal SECD, as well as concordance between ictal ICEEG and MRI lesion were significantly associated with seizure freedom. CONCLUSIONS: Ictal MEG can contribute useful information for delineating the resection area in epilepsy surgery. SIGNIFICANCE: Resection should include ictal, interictal SECDs and MRI lesion localization, when feasible. Concordant ictal and interictal SECDs on MEG can be a favorable predictor of seizure freedom.

Black Line Sign in Focal Cortical Dysplasia IIB: A 7T MRI and Electroclinicopathologic Study.

BACKGROUND AND OBJECTIVES: We aim to provide detailed imaging-electroclinicopathologic characterization of the black line sign, a novel MRI marker for focal cortical dysplasia (FCD) IIB. METHODS: 7T T2*-weighted gradient-echo (T2*w-GRE) images were retrospectively reviewed in a consecutive cohort of patients with medically intractable epilepsy with pathology-proven FCD II, for the occurrence of the black line sign. We examined the overlap between the black line region and the seizure-onset zone (SOZ) defined by intracranial EEG (ICEEG) and additionally assessed whether complete inclusion of the black line region in the surgical resection was associated with postoperative seizure freedom. The histopathologic specimen was aligned with the MRI to investigate the pathologic underpinning of the black line sign. Region-of-interest-based quantitative MRI (qMRI) analysis on the 7T T1 map was performed in the black line region, entire lesional gray matter (GM), and contralateral/ipsilateral normal gray and white matter (WM). RESULTS: We included 20 patients with FCD II (14 IIB and 6 IIA). The black line sign was identified in 12/14 (85.7%) of FCD IIB and 0/6 of FCD IIA on 7T T2*w-GRE. The black line region was highly concordant with the ICEEG-defined SOZ (5/7 complete and 2/7 partial overlap). Seizure freedom was seen in 8/8 patients whose black line region was completely included in the surgical resection; in the 2 patients whose resection did not completely include the black line region, both had recurring seizures. Inclusion of the black line region in the surgical resection was significantly associated with seizure freedom (p = 0.02). QMRI analyses showed that the T1 mean value of the black line region was significantly different from the WM (p < 0.001), but similar to the GM. Well-matched histopathologic slices in one case revealed accumulated dysmorphic neurons and balloon cells in the black line region. DISCUSSION: The black line sign may serve as a noninvasive marker for FCD IIB. Both MRI-pathology and qMRI analyses suggest that the black line region was an abnormal GM component within the FCD. Being highly concordant with ICEEG-defined SOZ and significantly associated with seizure freedom when included in resection, the black line sign may contribute to the planning of ICEEG/surgery of patients with medically intractable epilepsy with FCD IIB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in individuals with intractable focal epilepsy undergoing resection who have a 7T MRI with adequate image quality, the presence of the black line sign may suggest FCD IIB, be concordant with SOZ from ICEEG, and be associated with more seizure freedom if fully included in resection.

Characterizing thalamic and basal ganglia nuclei in medically intractable focal epilepsy by MR fingerprinting.

OBJECTIVES: Magnetic resonance fingerprinting (MRF) is a novel, quantitative, and noninvasive technique to measure brain tissue properties. We aim to use MRF for characterizing normal-appearing thalamic and basal ganglia nuclei in the epileptic brain. METHODS: A three-dimensional (3D) MRF protocol (1 mm3 isotropic resolution) was acquired from 48 patients with unilateral medically intractable focal epilepsy and 39 healthy controls (HCs). Whole-brain T1 and T2 maps (containing T1 and T2 relaxation times) were reconstructed for each subject. Ten subcortical nuclei in the thalamus and basal ganglia were segmented as regions of interest (ROIs), within which the mean T1 and T2 values, as well as their coefficient of variation (CV) were compared between the patients and HCs at the group level. Subgroup and correlation analyses were performed to examine the relationship between significant MRF measures and various clinical characteristics. Using significantly abnormal MRF measures from the group-level analyses, support vector machine (SVM) and logistic regression machine learning models were built and tested with 5-fold and 10-fold cross-validations, to separate patients from HCs, and to separate patients with left-sided and right-sided epilepsy, at the individual level. RESULTS: MRF revealed increased T1 mean value in the ipsilateral thalamus and nucleus accumbens; increased T1 CV in the bilateral thalamus, bilateral pallidum, and ipsilateral caudate; and increased T2 CV in the ipsilateral thalamus in patients compared to HCs (p < .05, false discovery rate [FDR] corrected). The SVM classifier produced 78.2% average accuracy to separate individual patients from HCs, with an area under the curve (AUC) of 0.83. The logistic regression classifier produced 67.4% average accuracy to separate patients with left-sided and right-sided epilepsy, with an AUC of 0.72. SIGNIFICANCE: MRF revealed bilateral tissue-property changes in the normal-appearing thalamus and basal ganglia, with ipsilateral predominance and thalamic preference, suggesting subcortical involvement/impairment in patients with medically intractable focal epilepsy. The individual-level performance of the MRF-based machine-learning models suggests potential opportunities for predicting lateralization.

Determinants of seizure outcome after resective surgery following stereoelectroencephalography.

OBJECTIVE: The aim of this study was to investigate seizure outcomes after resective epilepsy surgery following stereoelectroencephalography (SEEG), including group characteristics, comparing surgical and nonsurgical groups and assess predictors of time to seizure recurrence. METHODS: Clinical and EEG data of 536 consecutive patients who underwent SEEG at Cleveland Clinic Epilepsy Center between 2009 and 2017 were reviewed. The primary outcome was defined as complete seizure freedom since the resective surgery, discounting any auras or seizures that occurred within the 1st postoperative week. In addition, the rate of seizure freedom based on Engel classification was determined in patients with follow-up of ≥ 1 year. Presumably significant outcome variables were first identified using univariate analysis, and Cox proportional hazards modeling was used to identify outcome predictors. RESULTS: Of 527 patients satisfying study criteria, 341 underwent resective surgery. Complete and continuous seizure freedom after surgery was achieved in 55.5% of patients at 1 year postoperatively, 44% of patients at 3 years, and 39% of patients at 5 years. As a secondary outcome point, 58% of patients achieved Engel class I seizure outcome for at least 1 year at last follow-up. Among surgical outcome predictors, in multivariate model analysis, the seizure recurrence rate by type of resection (p = 0.039) remained statistically significant, with the lowest risk of recurrence occurring after frontal and temporal lobe resections compared with multilobar and posterior quadrant surgeries. Patients with a history of previous resection (p = 0.006) and bilateral implantations (p = 0.023) were more likely to have seizure recurrence. The absence of an MRI abnormality prior to resective surgery did not significantly affect seizure outcome in this cohort. CONCLUSIONS: This large, single-center series shows that resective surgery leads to continuous seizure freedom in a group of patients with complex and severe pharmacoresistant epilepsy after SEEG evaluation. In addition, up to 58% of patients achieved seizure freedom at last follow-up. The authors' results suggest that SEEG is equally effective in patients with frontal and temporal lobe epilepsy with or without MRI identified lesions.

The Efficacy and Use of a Pocket Card Algorithm in Status Epilepticus Treatment.

OBJECTIVE: To determine whether a pocket card treatment algorithm improves the early treatment of status epilepticus and to assess its utilization and retention in clinical practice. METHODS: Multidisciplinary care teams participated in video-recorded status epilepticus simulation sessions from 2015 to 2019. In this longitudinal cohort study, we examined the sessions recorded before and after introducing an internally developed, guideline-derived pocket card to determine differences in the adequacy or timeliness of rescue benzodiazepine. Simulation participants were queried 9 months later for submission of a differentiating identification number on each card to assess ongoing availability and utilization. RESULTS: Forty-four teams were included (22 before and 22 after the introduction of the pocket card). The time to rescue therapy was shorter for teams with the pocket card available (84 seconds [64-132]) compared with teams before introduction (144 seconds [100-162]) (U = 94; median difference = -46.9, 95% confidence interval [CI]: -75.9 to -21.9). The adequate dosing did not differ with card availability (odds ratio 1.48, 95% CI: 0.43-5.1). At the 9-month follow-up, 32 participants (65%) completed the survey, with 26 (81%) self-reporting having the pocket card available and 11 (34%) confirming ready access with the identification number. All identification numbers submitted corresponded to the hard copy laminated pocket card, and none to the electronic version. CONCLUSIONS: A pocket card is a feasible, effective, and worthwhile educational tool to improve the implementation of updated guidelines for the treatment of status epilepticus.

Individual localization value of resting-state fMRI in epilepsy presurgical evaluation: A combined study with stereo-EEG.

OBJECTIVE: To examine the individual-patient-level localization value of resting-state functional MRI (rsfMRI) metrics for the seizure onset zone (SOZ) defined by stereo-electroencephalography (SEEG) in patients with medically intractable focal epilepsies. METHODS: We retrospectively included 19 patients who underwent SEEG implantation for epilepsy presurgical evaluation. Voxel-wise whole-brain analysis was performed on 3.0 T rsfMRI to generate clusters for amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC), which were co-registered with the SEEG-defined SOZ to evaluate their spatial overlap. Subgroup and correlation analyses were conducted for various clinical characteristics. RESULTS: ALFF demonstrated concordant clusters with SEEG-defined SOZ in 73.7% of patients, with 93.3% sensitivity and 77.8% PPV. The concordance rate showed no significant difference when subgrouped by lesional/non-lesional MRI, SOZ location, interictal epileptiform discharges on scalp EEG, pathology or seizure outcomes. No significant correlation was seen between ALFF concordance rate and epilepsy duration, seizure-onset age, seizure frequency or number of antiseizure medications. ReHo and DC did not achieve favorable concordance results (10.5% and 15.8%, respectively). All concordant clusters showed regional activation, representing increased neural activities. CONCLUSION: ALFF had high concordance rate with SEEG-defined SOZ at individual-patient level. SIGNIFICANCE: ALFF activation on rsfMRI can add localizing information for the noninvasive presurgical workup of intractable focal epilepsies.

The Efficacy, Safety, and Outcomes of Brain-responsive Neurostimulation (RNS® System) therapy in older adults.

OBJECTIVES: The gold standard for the management of drug-resistant focal epilepsy (DRE) is resection of epileptogenic zone. However, some patients may not be candidates for resection. Responsive neurostimulation is approved in patients above 18 years of age for such patients. We aimed to investigate whether RNS outcomes and safety varied based on age. METHODS: We performed a single-center retrospective cohort study of patients with DRE who were treated with RNS between May 2008 and February 2020. We included patients who had been implanted with RNS for >6 months (N = 55), dividing them into older (N = 11) and younger adults (N = 44) depending on implantation age (≥50 and <50 years, respectively). RESULTS: Mean age at implantation in older adults was 54.9 ± 3.5 years. Seizure onset age, epilepsy duration, and comorbidities were significantly higher in older adults ( P < .01). Stimulation parameters, treatment duration, and median seizure frequency reduction (76% in older vs 50% in younger adults) were statistically comparable between the two cohorts. Posttreatment, antiseizure medication burden was significantly decreased in older compared with younger adults (P = .048). Postoperative and delayed adverse events among older adults were mild. Compared with three younger adults, none of the older adults required device explantation due to surgical site infection. CONCLUSION: Our study suggests that older adults treated with the RNS System achieve seizure outcomes comparable to younger adults with the additional benefit of a significant postimplantation medication reduction. With efficacy and safety similar to younger adults, brain-responsive neurostimulation was well-tolerated in older adults.

Multimodal Image Integration for Epilepsy Presurgical Evaluation: A Clinical Workflow.

Multimodal image integration (MMII) is a promising tool to help delineate the epileptogenic zone (EZ) in patients with medically intractable focal epilepsies undergoing presurgical evaluation. We report here the detailed methodology of MMII and an overview of the utility of MMII at the Cleveland Clinic Epilepsy Center from 2014 to 2018, exemplified by illustrative cases. The image integration was performed using the Curry platform (Compumedics Neuroscan™, Charlotte, NC, USA), including all available diagnostic modalities such as Magnetic resonance imaging (MRI), Positron Emission Tomography (PET), single-photon emission computed tomography (SPECT) and Magnetoencephalography (MEG), with additional capability of trajectory planning for intracranial EEG (ICEEG), particularly stereo-EEG (SEEG), as well as surgical resection planning. In the 5-year time span, 467 patients underwent MMII; of them, 98 patients (21%) had a history of prior neurosurgery and recurring seizures. Of the 467 patients, 425 patients underwent ICEEG implantation with further CT co-registration to identify the electrode locations. A total of 351 patients eventually underwent surgery after MMII, including 197 patients (56%) with non-lesional MRI and 223 patients (64%) with extra-temporal lobe epilepsy. Among 269 patients with 1-year post-operative follow up, 134 patients (50%) had remained completely seizure-free. The most common histopathological finding is focal cortical dysplasia. Our study illustrates the usefulness of MMII to enhance SEEG electrode trajectory planning, assist non-invasive/invasive data interpretation, plan resection strategy, and re-evaluate surgical failures. Information presented by MMII is essential to the understanding of the anatomo-functional-electro-clinical correlations in individual cases, which leads to the ultimate success of presurgical evaluation of patients with medically intractable focal epilepsies.

Neurovascular networks in epilepsy: Correlating ictal blood perfusion with intracranial electrophysiology.

Perfusion patterns observed in Subtraction Ictal SPECT Co-registered to MRI (SISCOM) assist in focus localization and surgical planning for patients with medically intractable focal epilepsy. While the localizing value of SISCOM has been widely investigated, its relationship to the underlying electrophysiology has not been extensively studied and is therefore not well understood. In the present study, we set to investigate this relationship in a cohort of 70 consecutive patients who underwent ictal and interictal SPECT studies and subsequent stereo-electroencephalography (SEEG) monitoring for localization of the epileptogenic focus and surgical intervention. Seizures recorded during SEEG evaluation (SEEG seizures) were matched to semiologically-similar seizures during the preoperative ictal SPECT evaluation (SPECT seizures) by comparing the semiological changes in the course of each seizure. The spectral changes of the ictal SEEG with respect to interictal ones over 7 traditional frequency bands (0.1 to 150Hz) were analyzed at each SEEG site. Neurovascular (SEEG/SPECT) relations were assessed by comparing the estimated spectral power density changes of the SEEG at each site with the perfusion changes (SISCOM z-scores) estimated from the acquired SISCOM map at that site. Across patients, a significant correlation (p<0.05) was observed between spectral changes during the SEEG seizure and SISCOM perfusion z-scores. Brain sites with high perfusion z-score exhibited higher increased SEEG power in theta to ripple frequency bands with concurrent suppression in delta and theta frequency bands compared to regions with lower perfusion z-score. The dynamics of the correlation of SISCOM perfusion and SEEG spectral power from ictal onset to seizure end and immediate postictal period were also derived. Forty-six (46) of the 70 patients underwent resective epilepsy surgery. SISCOM z-score and power increase in beta to ripple frequency bands were significantly higher in resected than non-resected sites in the patients who were seizure-free following surgery. This study provides for the first time concrete evidence that both hyper-perfusion and hypo-perfusion patterns observed in SISCOM maps have strong electrophysiological underpinnings, and that integration of the information from SISCOM and SEEG can shed light on the location and dynamics of the underlying epileptic brain networks, and thus advance our anatomo-electro-clinical understanding and approaches to targeted diagnostic and therapeutic interventions.

A Study of the Radiation Tolerance of CVD Diamond to 70 MeV Protons, Fast Neutrons and 200 MeV Pions.

We measured the radiation tolerance of commercially available diamonds grown by the Chemical Vapor Deposition process by measuring the charge created by a 120 GeV hadron beam in a 50 µm pitch strip detector fabricated on each diamond sample before and after irradiation. We irradiated one group of samples with 70 MeV protons, a second group of samples with fast reactor neutrons (defined as energy greater than 0.1 MeV), and a third group of samples with 200 MeV pions, in steps, to (8.8±0.9) × 1015 protons/cm2, (1.43±0.14) × 1016 neutrons/cm2, and (6.5±1.4) × 1014 pions/cm2, respectively. By observing the charge induced due to the separation of electron-hole pairs created by the passage of the hadron beam through each sample, on an event-by-event basis, as a function of irradiation fluence, we conclude all datasets can be described by a first-order damage equation and independently calculate the damage constant for 70 MeV protons, fast reactor neutrons, and 200 MeV pions. We find the damage constant for diamond irradiated with 70 MeV protons to be 1.62±0.07(stat)±0.16(syst)× 10-18 cm2/(p µm), the damage constant for diamond irradiated with fast reactor neutrons to be 2.65±0.13(stat)±0.18(syst)× 10-18 cm2/(n µm), and the damage constant for diamond irradiated with 200 MeV pions to be 2.0±0.2(stat)±0.5(syst)× 10-18 cm2/(π µm). The damage constants from this measurement were analyzed together with our previously published 24 GeV proton irradiation and 800 MeV proton irradiation damage constant data to derive the first comprehensive set of relative damage constants for Chemical Vapor Deposition diamond. We find 70 MeV protons are 2.60 ± 0.29 times more damaging than 24 GeV protons, fast reactor neutrons are 4.3 ± 0.4 times more damaging than 24 GeV protons, and 200 MeV pions are 3.2 ± 0.8 more damaging than 24 GeV protons. We also observe the measured data can be described by a universal damage curve for all proton, neutron, and pion irradiations we performed of Chemical Vapor Deposition diamond. Finally, we confirm the spatial uniformity of the collected charge increases with fluence for polycrystalline Chemical Vapor Deposition diamond, and this effect can also be described by a universal curve.

Value of 7T MRI and post-processing in patients with nonlesional 3T MRI undergoing epilepsy presurgical evaluation.

OBJECTIVE: Ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) offers increased signal-to-noise and contrast-to-noise ratios, which may improve visualization of cortical malformations. We aim to assess the clinical value of in vivo structural 7T MRI and its post-processing for the noninvasive identification of epileptic brain lesions in patients with pharmacoresistant epilepsy and nonlesional 3T MRI who are undergoing presurgical evaluation. METHODS: Sixty-seven patients were included who had nonlesional 3T MRI by official radiology report. Epilepsy protocols were used for the 3T and 7T acquisitions. Post-processing of the 7T T1-weighted magnetization-prepared two rapid acquisition gradient echoes sequence was performed using the morphometric analysis program (MAP) with comparison to a normal database consisting of 50 healthy controls. Review of 7T was performed by an experienced board-certified neuroradiologist and at the multimodal patient management conference. The clinical significance of 7T findings was assessed based on intracranial electroencephalography (ICEEG) ictal onset, surgery, postoperative seizure outcomes, and histopathology. RESULTS: Unaided visual review of 7T detected previously unappreciated subtle lesions in 22% (15/67). When aided by 7T MAP, the total yield increased to 43% (29/67). The location of the 7T-identified lesion was identical to or contained within the ICEEG ictal onset in 13 of 16 (81%). Complete resection of the 7T-identified lesion was associated with seizure freedom (P = .03). Histopathology of the 7T-identified lesions encountered mainly focal cortical dysplasia (FCD). 7T MAP yielded 25% more lesions (6/24) than 3T MAP, and showed improved conspicuity in 46% (11/24). SIGNIFICANCE: Our data suggest a major benefit of 7T with post-processing for detecting subtle FCD lesions for patients with pharmacoresistant epilepsy and nonlesional 3T MRI.

Investigation of networks underlying hyperkinetic seizures utilizing ictal SPECT.

OBJECTIVE: To study neural networks involved in hyperkinetic seizures (HKS) using ictal SPECT. METHODS: We retrospectively identified 18 patients with HKS evaluated at the Cleveland Clinic between 2005 and 2015 with video-EEG monitoring and ictal SPECT. Semiology was confirmed by the consensus of 2 epileptologists' independent reviews and classified as type 1, 2, or 3 HKS. SPECT data were analyzed by 2 independent physicians using a z score of 1.5. Ictal hyperperfusion patterns for each group were analyzed visually and with SPM. Spatial normalization to Montreal Neurological Institute space for each patient's data was performed, followed by flipping of data from patients with left-sided ictal onset to the right side. Finally, an average z score map for each group was calculated. RESULTS: Visual analysis and SPM identified different patterns of ictal hyperperfusion in the 3 subtypes of HKS. Type 1 seizures showed hyperperfusion in a more anteriorly located network involving the anterior insula, orbitofrontal cortex, cingulate, and anterior perisylvian region and rostral midbrain. Type 2 seizures were associated with hyperperfusion in a more caudally located network involving the orbitofrontal cortex, cingulate (middle and posterior), basal ganglia, thalami, and cerebellum. Type 3 seizures showed a mixed pattern of SPECT hyperperfusion involving the temporal pole and anterior perisylvian region. CONCLUSIONS: Each of the 3 different semiologic subtypes of HKS is associated with distinct patterns of hyperperfusion, providing further insight into the neural networks involved. This knowledge may inform placement of invasive EEG electrodes in patients with HKS semiology undergoing presurgical evaluation.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Localization value of subclinical seizures on scalp video-EEG in epilepsy presurgical evaluation.

OBJECTIVE: To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery. METHODS: We included 123 consecutive patients who had SCSs and CSs during scalp-VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1-year follow-up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome. RESULTS: Sixty-nine patients (56.1%) had seizure-free outcome at 1-year follow-up. In 68 patients (55.3%), the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure-free outcome at 1-year (P = .020) and 2-year follow-up (P = .040). In the temporal lobe epilepsy (TLE) seizure-free group, SCS localization was completely contained within the resection in 44.4% and CS localization was completely contained within the resection in 41.7%; in the extratemporal lobe epilepsy (ETLE) seizure-free group, SCS localization was completely contained within the resection in 54.5% and CS localization was completely contained within the resection in 57.6%. SIGNIFICANCE: Complete concordance between CS and SCS localization is a positive prognostic factor for 1-year and 2-year postoperative seizure-free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.