Extraoperative Electrocorticography Research Articles

Effect of Sevoflurane Anesthesia on Intraoperative Spikes, High-Frequency Oscillations, and Phase-Amplitude Coupling in MRI-Normal Hippocampus.

The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFOs), and phase-amplitude coupling using a modulation index in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography in identifying the epileptogenic hippocampus during sevoflurane administration. Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography evaluation. Patients were assigned to the Ictal (+) or Ictal (-) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. Intraoperative electrocorticography was performed under 0.5 and 1.5 minimum alveolar concentration of sevoflurane. The rates of spikes, ripples, fast ripples (FRs), ripples on spikes, FRs on spikes, and MI HFO(3-4 Hz) were evaluated. During the intraoperative electrocorticography procedure, sevoflurane administration was found to significantly increase the rate of spikes, ripples on spikes, fast ripples on spikes, and MI HFO(3-4 Hz) in the Ictal (+) group ( P < 0.01). By contrast, the Ictal (-) group exhibited a paradoxical increase in the rate of ripples and fast ripple ( P < 0.05). Our findings indicate that the administration of sevoflurane during intraoperative electrocorticography in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, ripples on spikes, fast ripples on spikes, and MI (HFO 3-4) ) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and fast ripple in the nonepileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the nonepileptogenic hippocampus.

Left Temporal Pole Encephalocele With Independent Hippocampal Seizures: Surgical Strategy and Relevance of Epileptic Biomarkers.

Temporal pole encephalocele (TE) is an increasingly recognized surgically treatable subtype of refractory temporal lobe epilepsy that rarely shows hippocampal involvement. A 27-year-old patient presented with medically intractable epilepsy because of a left temporal pole encephalocele with a normal hippocampus on MRI. Extraoperative electrocorticography showed independent seizure onset with distinct morphology of seizure onset pattern from the temporal pole encephalocele and hippocampus. Additional analysis of ictal and interictal fast ripples revealed different electrophysiological fast ripple profiles in the two seizure onset zones. The patient underwent temporopolar disconnection, eliminating the need for large dural repair and multiple hippocampal transections that helped preserve the intrahippocampal and extrahippocampal memory pathways. Herein, the authors report that independent hippocampal seizures can be observed in patients with temporal pole encephalocele. Features of the ictal and interictal fast ripples can differ depending on the morphology of the seizure onset pattern. The authors suggest that, the interpretation of fast ripples in clinical practice should take seizure onset patterns into consideration.

Developmental organization of neural dynamics supporting auditory perception

Purpose: A prominent view of language acquisition involves learning to ignore irrelevant auditory signals through functional reorganization, enabling more efficient processing of relevant information. Yet, few studies have characterized the neural spatiotemporal dynamics supporting rapid detection and subsequent disregard of irrelevant auditory information, in the developing brain. To address this unknown, the present study modeled the developmental acquisition of cost-efficient neural dynamics for auditory processing, using intracranial electrocorticographic responses measured in individuals receiving standard-of-care treatment for drug-resistant, focal epilepsy. We also provided evidence demonstrating the maturation of an anterior-to-posterior functional division within the superior-temporal gyrus (STG), which is known to exist in the adult STG. Methods: We studied 32 patients undergoing extraoperative electrocorticography (age range: eight months to 28 years) and analyzed 2,039 intracranial electrode sites outside the seizure onset zone, interictal spike-generating areas, and MRI lesions. Patients were given forward (normal) speech sounds, backward-played speech sounds, and signal-correlated noises during a task-free condition. We then quantified sound processing-related neural costs at given time windows using high-gamma amplitude at 70–110 Hz and animated the group-level high-gamma dynamics on a spatially normalized three-dimensional brain surface. Finally, we determined if age independently contributed to high-gamma dynamics across brain regions and time windows. Results: Group-level analysis of noise-related neural costs in the STG revealed developmental enhancement of early high-gamma augmentation and diminution of delayed augmentation. Analysis of speech-related high-gamma activity demonstrated an anterior-to-posterior functional parcellation in the STG. The left anterior STG showed sustained augmentation throughout stimulus presentation, whereas the left posterior STG showed transient augmentation after stimulus onset. We found a double dissociation between the locations and developmental changes in speech sound-related high-gamma dynamics. Early left anterior STG high-gamma augmentation (i.e., within 200 ms post-stimulus onset) showed developmental enhancement, whereas delayed left posterior STG high-gamma augmentation declined with development. Conclusions: Our observations support the model that, with age, the human STG refines neural dynamics to rapidly detect and subsequently disregard uninformative acoustic noises. Our study also supports the notion that the anterior-to-posterior functional division within the left STG is gradually strengthened for efficient speech-sound perception after birth.

Six-dimensional dynamic tractography atlas of language connectivity in the developing brain.

During a verbal conversation, our brain moves through a series of complex linguistic processing stages: sound decoding, semantic comprehension, retrieval of semantically coherent words, and overt production of speech outputs. Each process is thought to be supported by a network consisting of local and long-range connections bridging between major cortical areas. Both temporal and extratemporal lobe regions have functional compartments responsible for distinct language domains, including the perception and production of phonological and semantic components. This study provides quantitative evidence of how directly connected inter-lobar neocortical networks support distinct stages of linguistic processing across brain development. Novel six-dimensional tractography was used to intuitively visualize the strength and temporal dynamics of direct inter-lobar effective connectivity between cortical areas activated during each linguistic processing stage. We analysed 3401 non-epileptic intracranial electrode sites from 37 children with focal epilepsy (aged 5-20 years) who underwent extra-operative electrocorticography recording. Principal component analysis of auditory naming-related high-gamma modulations determined the relative involvement of each cortical area during each linguistic processing stage. To quantify direct effective connectivity, we delivered single-pulse electrical stimulation to 488 temporal and 1581 extratemporal lobe sites and measured the early cortico-cortical spectral responses at distant electrodes. Mixed model analyses determined the effects of naming-related high-gamma co-augmentation between connecting regions, age, and cerebral hemisphere on the strength of effective connectivity independent of epilepsy-related factors. Direct effective connectivity was strongest between extratemporal and temporal lobe site pairs, which were simultaneously activated between sentence offset and verbal response onset (i.e. response preparation period); this connectivity was approximately twice more robust than that with temporal lobe sites activated during stimulus listening or overt response. Conversely, extratemporal lobe sites activated during overt response were equally connected with temporal lobe language sites. Older age was associated with increased strength of inter-lobar effective connectivity especially between those activated during response preparation. The arcuate fasciculus supported approximately two-thirds of the direct effective connectivity pathways from temporal to extratemporal auditory language-related areas but only up to half of those in the opposite direction. The uncinate fasciculus consisted of <2% of those in the temporal-to-extratemporal direction and up to 6% of those in the opposite direction. We, for the first time, provided an atlas which quantifies and animates the strength, dynamics, and direction specificity of inter-lobar neural communications between language areas via the white matter pathways. Language-related effective connectivity may be strengthened in an age-dependent manner even after the age of 5.

Spontaneous modulations of high-frequency cortical activity

ObjectiveWe clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state. MethodsWe studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70–110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation. ResultsThe dynamic atlas demonstrated transient high-gamma suppression in the striatal cortex before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%. ConclusionsWe successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades. SignificanceMeasuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic.

Combining Gamma With Alpha and Beta Power Modulation for Enhanced Cortical Mapping in Patients With Focal Epilepsy.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55–200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8–12 Hz) and beta (15–25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22–48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.

Neural dynamics during the vocalization of \u2018uh\u2019 or \u2018um\u2019

People occasionally use filler phrases or pauses, such as “uh”, “um”, or “y’know,” that interrupt the flow of a sentence and fill silent moments between ordinary (non-filler) phrases. It remains unknown which brain networks are engaged during the utterance of fillers. We addressed this question by quantifying event-related cortical high gamma activity at 70–110 Hz. During extraoperative electrocorticography recordings performed as part of the presurgical evaluation, patients with drug-resistant focal epilepsy were instructed to overtly explain, in a sentence, ‘what is in the image (subject)’, ‘doing what (verb)’, ‘where (location)’, and ‘when (time)’. Time–frequency analysis revealed that the utterance of fillers, compared to that of ordinary words, was associated with a greater magnitude of high gamma augmentation in association and visual cortex of either hemisphere. Our preliminary results raise the hypothesis that filler utterance would often occur when large-scale networks across the association and visual cortex are engaged in cognitive processing, including lexical retrieval as well as verbal working memory and visual scene scanning.

Clinical Relevance of Interictal Spikes in Tumor-Related Epilepsy: An Electrocorticographic Study.

Background and PurposeAlthough some surgeons utilize interictal spikes recorded via electrocorticography (ECoG) when planning extensive peritumoral resection in patients with tumor-related epilepsy, the association between interictal spikes and epileptogenesis has not been fully described. We investigated whether the resection of interictal spikes recorded by ECoG is associated with more favorable surgical outcomes in tumor-related epilepsy.MethodsOf 132 patients who underwent epilepsy surgery for tumor-related epilepsy from 2006 to 2013, seven patients who underwent extraoperative ECoG were included in this study. In each patient, ECoG interictal spike sources were localized using standardized low-resolution brain electromagnetic tomography and were co-registered into a reconstructed brain model. Correspondence to the resection volume was estimated by calculating the percentage of interictal spike sources in the resection volume.ResultsAll patients achieved gross total resection without oncological recurrence. Five patients achieved favorable surgical outcomes, whereas the surgical outcomes of two patients were unfavorable. Correspondence rates to the resection volume in the favorable and unfavorable surgical outcome groups were 44.6%±27.8% and 43.5%±22.8%, respectively (p=0.96). All patients had interictal spike source clusters outside the resection volume regardless of seizure outcome.ConclusionsIn these cases of tumor-related epilepsy, the extent of the resection of ECoG interictal spikes was not associated with postoperative seizure outcomes. Furthermore, the presence of interictal spike sources outside of the resection area was not related to seizure outcomes. Instead, concentrating more on the complete removal of the brain tumor appears to be a rational approach.

Prospective observational study: Fast ripple localization delineates the epileptogenic zone

ObjectiveTo investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom. MethodsInterictal fast ripples (FRs: 250–500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI. ResultsInterictal FRs were observed in all patients except one. Thirteen out of 18 patients (72%) exhibited FRs beyond the extent of neuroimaging abnormalities. Fifteen of 19 children underwent resective surgery, and survival analysis with log-rank test demonstrated that complete resection of cortical sites showing interictal FRs correlated with longer post-operative seizure-freedom (p < 0.01). Complete resection of seizure onset zones (SOZ) also correlated with longer post-operative seizure-freedom (p = 0.01), yet complete resection of neuroimaging abnormalities did not (p = 0.43). ConclusionsProspective visual analysis of interictal FRs was feasible, and it seemed to accurately localize epileptogenic zones. SignificanceTopological extent of epileptogenic region may exceed what is discernible by multimodal neuroimaging.

Four-dimensional functional cortical maps of visual and auditory language: Intracranial recording.

The strength of presurgical language mapping using electrocorticography (ECoG) is its outstanding signal fidelity and temporal resolution, but the weakness includes limited spatial sampling at an individual patient level. By averaging naming-related high-gamma activity at nonepileptic regions across a large number of patients, we provided the functional cortical atlases animating the neural dynamics supporting visual-object and auditory-description naming at the whole brain level. We studied 79 patients who underwent extraoperative ECoG recording as epilepsy presurgical evaluation, and generated time-frequency plots and animation videos delineating the dynamics of naming-related high-gamma activity at 70-110 Hz. Naming task performance elicited high-gamma augmentation in domain-specific lower-order sensory areas and inferior-precentral gyri immediately after stimulus onset. High-gamma augmentation subsequently involved widespread neocortical networks with left hemisphere dominance. Left posterior temporal high-gamma augmentation at several hundred milliseconds before response onset exhibited a double dissociation; picture naming elicited high-gamma augmentation preferentially in regions medial to the inferior-temporal gyrus, whereas auditory naming elicited high-gamma augmentation more laterally. The left lateral prefrontal regions including Broca's area initially exhibited high-gamma suppression subsequently followed by high-gamma augmentation at several hundred milliseconds before response onset during both naming tasks. Early high-gamma suppression within Broca's area was more intense during picture compared to auditory naming. Subsequent lateral-prefrontal high-gamma augmentation was more intense during auditory compared to picture naming. This study revealed contrasting characteristics in the spatiotemporal dynamics of naming-related neural modulations between tasks. The dynamic atlases of visual and auditory language might be useful for planning of epilepsy surgery. Differential neural activation well explains some of the previously reported observations of domain-specific language impairments following resective epilepsy surgery. Video materials might be beneficial for the education of lay people about how the brain functions differentially during visual and auditory naming.

Phase‐amplitude coupling between interictal high‐frequency activity and slow waves in epilepsy surgery

We hypothesized that the modulation index (MI), a summary measure of the strength of phase-amplitude coupling between high-frequency activity (>150Hz) and the phase of slow waves (3-4Hz), would serve as a useful interictal biomarker for epilepsy presurgical evaluation. We investigated 123 patients who underwent focal cortical resection following extraoperative electrocorticography recording and had at least 1 year of postoperative follow-up. We examined whether consideration of MI would improve the prediction of postoperative seizure outcome. MI was measured at each intracranial electrode site during interictal slow-wave sleep. We compared the accuracy of prediction of patients achieving International League Against Epilepsy class 1 outcome between the full multivariate logistic regression model incorporating MI in addition to conventional clinical, seizure onset zone (SOZ), and neuroimaging variables, and the reduced logistic regression model incorporating all variables other than MI. Ninety patients had class 1 outcome at the time of most recent follow-up (mean follow-up = 5.7years). The full model had a noteworthy outcome predictive ability, as reflected by regression model fit R2 of 0.409 and area under the curve (AUC) of receiver operating characteristic plot of 0.838. Incomplete resection of SOZ (P<0.001), larger number of antiepileptic drugs at the time of surgery (P=0.007), and larger MI in nonresected tissues relative to that in resected tissue (P=0.020) were independently associated with a reduced probability of class 1 outcome. The reduced model had a lower predictive ability as reflected by R2 of 0.266 and AUC of 0.767. Anatomical variability in MI existed among nonepileptic electrode sites, defined as those unaffected by magnetic resonance imaging lesion, SOZ, or interictal spike discharges. With MI adjusted for anatomical variability, the full model yielded the outcome predictive ability of R2 of 0.422, AUC of 0.844, and sensitivity/specificity of 0.86/0.76. MI during interictal recording may provide useful information for the prediction of postoperative seizure outcome.

T149. After-discharges and seizures during functional brain mapping with extra-operative electrical cortical stimulation

Electrical cortical stimulation (ECS) is the clinical standard for brain mapping to define the relationship between seizure-onset zone and functionally eloquent cortex in patients undergoing presurgical evaluation with intracranial electrodes. ECS-induced after-discharges (ADs) and seizures contribute to the morbidity and compromise the validity of ECS results. This study examines the incidence, thresholds, and determinants of ECS-induced ADs and seizures. A retrospective review of clinical information and extra-operative electrocorticography (ECoG) recordings was performed in pediatric patients to determine incidence and thresholds of ECS-induced Ads and seizures. Multivariate models were used to evaluate predictors of AD and seizure occurrence and their thresholds. A total of 122 children were included. The incidence of ADs and seizures were 77% (94/122) and 35% (43/122) respectively. Males (OR 2.92, 95% CI 1.21–7.38, p = 0.02) and patients with MRI-negative epilepsy (OR 3.69, 95% CI 1.24–13.7, p = 0.03) had increased odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient 0.151, p = 0.011). ECSinduced seizures were more likely to occur in patients with lateralized positron emission tomography (OR 6.62, 95% CI 1.36–55.56, p = 0.036) and presence of ADs (OR 3.50, 95% CI 1.12–13.36, p = 0.043). ECS functional brain mapping is associated with a high incidence of ADs and seizures. Increasing age is significantly associated with decreasing current thresholds and increased probability of occurrence of ADs and seizures. These findings underscore the need to develop safer method(s) for mapping brain function, particularly in children.

F178. Epilepsy and temporal encephaloceles: Presurgical evaluation and surgical outcomes

Introduction Temporal encephalocele (TE) is an under-recognized surgically-remediable cause of medically refractory temporal lobe epilepsy. This study assessed preoperative evaluations [MRI, FDG-PET, routine and prolonged video scalp EEG, intraoperative and extraoperative electrocorticography (ECog)] and short-term surgical outcomes in patients with medically refractory temporal lobe epilepsy due to TE. Methods Patients with medically refractory temporal lobe epilepsy who underwent surgical intervention for known TE at the Mayo Clinic Rochester between January 2008 and July 2017 were identified. Additional patients who underwent surgery for temporal lobe epilepsy were found retrospectively on review of PET-CT or PET-MRI by an experienced neuroradiologist. Minimum required follow-up was 3 months. Results Fifteen patients were identified (female 80%, median age 42.1 years, interquartile range (IQR) 19.3–54.9 years). TE was identified in 7 patients prior to surgery (left 3, right 2, bilateral 2), from radiology re-review in 7 (left 1, right 1, bilateral 5), and intraoperatively in 1 (right). Temporal hypometabolism was present on FDG-PET in 7 of 10 patients, including 5 initial MRI reviews not suggestive of TE. Routine EEG was normal in 7 patients (47%). Prolonged video EEG showed interictal discharges and ictal onset ipsilateral to the TE in all unilateral cases. In bilateral TE, temporal interictal discharges were lateralized in 4 patients and focal ictal onset present in 5 patients. Intraoperative or extraoperative ECog showed widespread mesial and neocortical temporal discharges in 12 of 14 patients. Three patients (20%) underwent focal TE resection, 11 patients (73.3%) anterior temporal lobectomy (ATL), and 1 patient amygdalohippocampal laser ablation. Eight patients (53.3%) were seizure-free at last follow-up (median follow-up duration 7.1 months, IQR 4.2–41.9, 1 focal TE resection, 7 ATL). Focal TE resection was performed only in recent years (median duration of follow-up in focal TE resection 7.2 months, IQR 7–13.8, versus ATL 18.7 months, IQR 4.1–48.8), and comparison of surgical outcome between surgical groups was limited to short-term follow-up. At 6 months, seizure-freedom was achieved in 2 of 3 patient with focal TE resection and 4 of 6 patients with ATL (p > 0.05). Conclusion TE is an easily overlooked etiology of medically refractory temporal lobe epilepsy. Normal routine EEG and unrevealing initial MRI review were seen in nearly half of the patients. Although prolonged video scalp EEG provided concordant localizing information consistent with TE, ECog often showed epileptogenic discharges extending beyond regions around the TE and should be interpreted with caution as short-term follow up remained favorable despite focal TE resection. Long-term follow-up is needed to clarify which surgical approach optimizes seizure outcome while minimizing resection.

BS25. Language inhibition and motor response thresholds during extra-operative cortical stimulation mapping

Introduction Electrical cortical stimulation (ECS) is the clinical standard for brain mapping to define the functionally eloquent cortex in patients undergoing pre-surgical evaluation with intracranial electrodes. This study evaluated thresholds for language inhibition and motor response during ECS and their determinants. Methods A retrospective review of clinical information and extra-operative electrocorticography (ECoG) recordings was performed. The thresholds for functional responses were determined and compared with after-discharge (AD) thresholds. Multivariate models were used to evaluate predictors of functional thresholds. Results A total of 122 children were included. The mean language threshold was 7.4 ( ± 3.0) mA. 40/47 (85%) of patients with language response during ECS also had ADs. Language thresholds were found to be equal to or higher than AD thresholds in 34/40 (85%) patients. The mean motor threshold was 5.4 ( ± 2.8) mA. 71/85(83.5%) of patients with motor response during ECS also had ADs. Motor thresholds were found to be equal to or higher than AD thresholds in 47/71 (66%) patients. Minimum AD threshold was a significant determinant of minimum language threshold (regression co-efficient 0.446, 95% CI −0.001 to 0.892, p = 0.050) and minimum motor threshold (regression co-efficient 0.664, 95%CI 0.058 to 1.270, p = 0.034). Conclusion AD threshold was a significant determinant of language and motor thresholds. Most children with functional response during ECS also had ADs, with the functional thresholds being equal to or higher than AD thresholds. These findings underscore a potential pitfall in functional cortex localization with ECS findings and emphasize the need for a functional mapping method with improved neurophysiologic validity, especially in children.

Intraoperative fast ripples independently predict postsurgical epilepsy outcome: Comparison with other electrocorticographic phenomena

In the surgical management of epilepsy, the resection of cortex exhibiting interictal fast ripples (250–500Hz) on electrocorticography has been linked to postoperative seizure-freedom. Although fast ripples appear to accurately identify the epileptogenic zone—the minimum tissue that must be removed at surgery to achieve seizure-freedom—it has not been established that fast ripples are a superior biomarker in comparison with multimodal presurgical neuroimaging and other electrocorticography abnormalities. Hence, in the prediction of postoperative seizure-freedom, we compared the value of fast ripples with other intraoperative electocorticography abnormalities including focal slowing, paroxysmal fast activity, intermittent spike discharges, continuous epileptiform discharges, focal attenuation, and intraoperative seizures, as well as complete resection of the lesion defined by MRI and other neuroimaging. In a cohort of 60 children with lesional epilepsy and median postsurgical follow-up exceeding 4 years, who underwent resective epilepsy surgery with intraoperative electrocorticography, we evaluated the extent to which removal of each intraoperative electrocorticography abnormality impacts time to first postoperative seizure using the Kaplan-Meier method and Cox proportional hazards regression. Secondly, we contrasted the predictive value of resection of each competing electrocorticography abnormality using standard test metrics (sensitivity, specificity, positive predictive value, and negative predictive value). In contrast with all other intraoperative electrocorticography abnormalities, fast ripples demonstrated the most favorable combination of positive predictive value (100%) and negative predictive value (76%) in the prediction of postoperative seizures. Among all candidate electrocorticography features, time to first postoperative seizure was most strongly associated with incomplete resection of fast ripples (hazard ratio=19.8, p<0.001). In multivariate survival analyses, postoperative seizures were independently predicted by incomplete resection of cortex generating fast ripples (hazard ratio=25.4, 95%CI 6.71–96.0, p<0.001) and focal slowing (hazard ratio=5.79, 95%CI 1.76–19.0, p=0.004), even after adjustment for the impact of an otherwise complete resection. All children with incomplete resection of interictal FR-generating cortex exhibited postoperative seizures within six months. Notably, this cohort included many patients with large resections and thus limited opportunity to exhibit unresected fast ripples. Future study in a cohort with small resection volume, or a clinical trial in which resection margins are guided by fast ripple distribution, would likely yield a more precise estimate of the risk posed by unresected fast ripples. With a high detection rate during brief intraoperative electrocorticography and favorable positive and negative predictive value, interictal fast ripple characterization during surgery is a feasible and useful adjunct to standard methods for epilepsy surgery planning, and represents a valuable spatially-localizing biomarker of the epileptogenic zone, without the need for prolonged extraoperative electrocorticography.

Interictal high-frequency oscillations generated by seizure onset and eloquent areas may be differentially coupled with different slow waves.

High-frequency oscillations (HFOs) can be spontaneously generated by seizure-onset and functionally-important areas. We determined if consideration of the spectral frequency bands of coupled slow-waves could distinguish between epileptogenic and physiological HFOs. We studied a consecutive series of 13 children with focal epilepsy who underwent extraoperative electrocorticography. We measured the occurrence rate of HFOs during slow-wave sleep at each electrode site. We subsequently determined the performance of HFO rate for localization of seizure-onset sites and undesirable detection of nonepileptic sensorimotor-visual sites defined by neurostimulation. We likewise determined the predictive performance of modulation index: MI(XHz)&(YHz), reflecting the strength of coupling between amplitude of HFOsXHz and phase of slow-waveYHz. The predictive accuracy was quantified using the area under the curve (AUC) on receiver-operating characteristics analysis. Increase in HFO rate localized seizure-onset sites (AUC⩾0.72; p<0.001), but also undesirably detected nonepileptic sensorimotor-visual sites (AUC⩾0.58; p<0.001). Increase in MI(HFOs)&(3-4Hz) also detected both seizure-onset (AUC⩾0.74; p<0.001) and nonepileptic sensorimotor-visual sites (AUC⩾0.59; p<0.001). Increase in subtraction-MIHFOs [defined as subtraction of MI(HFOs)&(0.5-1Hz) from MI(HFOs)&(3-4Hz)] localized seizure-onset sites (AUC⩾0.71; p<0.001), but rather avoided detection of nonepileptic sensorimotor-visual sites (AUC⩽0.42; p<0.001). Our data suggest that epileptogenic HFOs may be coupled with slow-wave3-4Hz more preferentially than slow-wave0.5-1Hz, whereas physiologic HFOs with slow-wave0.5-1Hz more preferentially than slow-wave3-4Hz during slow-wave sleep. Further studies in larger samples are warranted to determine if consideration of the spectral frequency bands of slow-waves coupled with HFOs can positively contribute to presurgical evaluation of patients with focal epilepsy.

Major and minor complications in extraoperative electrocorticography: A review of a national database

The risk profile of extraoperative electrocorticography (ECoG) is documented almost exclusively by case series from a limited number of academic medical centers. These studies tend to underreport minor complications, like urinary tract infections (UTIs) and deep venous thromboses (DVTs), that nevertheless affect hospital cost, length of stay, and the patient's quality of life. Herein, we used data from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) to estimate the rate of adverse events in extraoperative ECoG surgeries. NSQIP is a validated dataset containing nearly 3 million procedures from over 600 North American hospitals, and uses strict criteria for the documentation of complications. Major complications occurred in 3.4% of 177 extraoperative ECoG cases, while minor complications occurred in 9.6%. The most common minor complication was bleeding requiring a transfusion in 3.4% of cases, followed by sepsis, DVT, and UTI each in 2.3% of cases. No mortality was reported. Overall, in a national database containing a heterogeneous population of hospitals, major complications of extraoperative ECoG were rare (3.4%). Complications such as UTI and DVT tend to be underreported in retrospective case series, yet make up a majority of minor complications for ECoG patients in this dataset.

Intraoperative mapping of expressive language cortex using passive real-time electrocorticography.

In this case report, we investigated the utility and practicality of passive intraoperative functional mapping of expressive language cortex using high-resolution electrocorticography (ECoG). The patient presented here experienced new-onset seizures caused by a medium-grade tumor in very close proximity to expressive language regions. In preparation of tumor resection, the patient underwent multiple functional language mapping procedures. We examined the relationship of results obtained with intraoperative high-resolution ECoG, extraoperative ECoG utilizing a conventional subdural grid, extraoperative electrical cortical stimulation (ECS) mapping, and functional magnetic resonance imaging (fMRI). Our results demonstrate that intraoperative mapping using high-resolution ECoG is feasible and, within minutes, produces results that are qualitatively concordant to those achieved by extraoperative mapping modalities. They also suggest that functional language mapping of expressive language areas with ECoG may prove useful in many intraoperative conditions given its time efficiency and safety. Finally, they demonstrate that integration of results from multiple functional mapping techniques, both intraoperative and extraoperative, may serve to improve the confidence in or precision of functional localization when pathology encroaches upon eloquent language cortex.

Temporal lobe epilepsy and cavernous malformations: surgical strategies and long-term outcomes.

Cerebral cavernous malformations (CCM) of the temporal lobe often present with seizures. Surgical resection of these lesions can offer durable seizure control. There is, however, no universally accepted methodology for assessing and surgically treating these patients. We propose an algorithm to maximize positive surgical outcomes (seizure control) while minimizing post-surgical neurological deficit. A retrospective review of 34 patients who underwent epilepsy surgery for radiographically proven temporal lobe CCM was conducted. Patients underwent a relatively standard work-up for seizure localization. In patients with mesial temporal lobe epilepsy (MTLE), a complete resection of the epileptogenic zone was performed including amygdalo-hippocampectomy in addition to a lesionectomy if not contraindicated by pre-operative work-up. Patients with neocortical epilepsy underwent intraoperative electrocorticography (ECoG)-guided lesionectomy. Seizure-free rate for mesial and neocortical (anterior, lateral, and basal) location was 90 vs. 83 %, respectively. Complete resection of the lesion, irrespective of location, was statistically significant for seizure control (p = 0.018). There was no difference in seizure control based on disease duration or location (p > 0.05). Patients with mesial temporal CCM who presented with MTLE were presumed to also have mesial temporal sclerosis (MTS), or dual pathology. These patients underwent routine resection of the mesial structures. Interestingly, patients who had MTLE and basal (neocortical) lesions who underwent a mesial resection for suspected MTS were found not to have dual pathology. Patients with temporal lobe CCM should be offered resection for durable seizure control, prevention of secondary epileptogenic foci, and elimination of hemorrhage risk. The preoperative work-up should follow a team approach. Surgical intervention should include complete lesionectomy in all cases. Intra or extra-operative ECoG for neocortical lesions may be beneficial. Management of mesial temporal CCMs (archicortex) should consider resection of a well-defined epileptogenic zone (including mesial structures) due to high probability of pathologically proven MTS. The use of this treatment algorithm is useful for the education and treatment of these patients.

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.