Distinct patterns of interictal intracranial EEG in focal cortical dysplasia type I and II.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common malformation causing refractory focal epilepsy. Surgical removal of the entire dysplastic cortex is crucial for achieving a seizure-free outcome. Precise presurgical distinctions between FCD types by neuroimaging are difficult, mainly in patients with normal magnetic resonance imaging findings. However, the FCD type is important for planning the extent of surgical approach and counselling. METHODS: This study included patients with focal drug-resistant epilepsy and definite histopathological FCD type I or II diagnoses who underwent intracranial electroencephalography (iEEG). We detected interictal epileptiform discharges (IEDs) and their recruitment into repetitive discharges (RDs) to compare electrophysiological patterns characterizing FCD types. RESULTS: Patients with FCD type II had a significantly higher IED rate (p < 0.005), a shorter inter-discharge interval within RD episodes (p < 0.003), sleep influence on decreased RD periodicity (p < 0.036), and longer RD episode duration (p < 0.003) than patients with type I. A Bayesian classifier stratified FCD types with 82% accuracy. CONCLUSION: Temporal characteristics of IEDs and RDs reflect the histological findings of FCD subtypes and can differentiate FCD types I and II. SIGNIFICANCE: Presurgical prediction of FCD type can help to plan a more tailored surgical approach in patients with normal magnetic resonance findings.

The Relationship Between Seizures and Spreading Depolarizations in Patients with Severe Traumatic Brain Injury.

BACKGROUND: Both seizures and spreading depolarizations (SDs) are commonly detected using electrocorticography (ECoG) after severe traumatic brain injury (TBI). A close relationship between seizures and SDs has been described, but the implications of detecting either or both remain unclear. We sought to characterize the relationship between these two phenomena and their clinical significance. METHODS: We performed a post hoc analysis of a prospective observational clinical study of patients with severe TBI requiring neurosurgery at five academic neurotrauma centers. A subdural electrode array was placed intraoperatively and ECoG was recorded during intensive care. SDs, seizures, and high-frequency background characteristics were quantified offline using published standards and terminology. The primary outcome was the Glasgow Outcome Scale-Extended score at 6 months post injury. RESULTS: There were 138 patients with valid ECoG recordings; the mean age was 47 ± 19 years, and 104 (75%) were men. Overall, 2,219 ECoG-detected seizures occurred in 38 of 138 (28%) patients in a bimodal pattern, with peak incidences at 1.7-1.8 days and 3.8-4.0 days post injury. Seizures detected on scalp electroencephalography (EEG) were diagnosed by standard clinical care in only 18 of 138 (13%). Of 15 patients with ECoG-detected seizures and contemporaneous scalp EEG, seven (47%) had no definite scalp EEG correlate. ECoG-detected seizures were significantly associated with the severity and number of SDs, which occurred in 83 of 138 (60%) of patients. Temporal interactions were observed in 17 of 24 (70.8%) patients with both ECoG-detected seizures and SDs. After controlling for known prognostic covariates and the presence of SDs, seizures detected on either ECoG or scalp EEG did not have an independent association with 6-month functional outcome but portended worse outcome among those with clustered or isoelectric SDs. CONCLUSIONS: In patients with severe TBI requiring neurosurgery, seizures were half as common as SDs. Seizures would have gone undetected without ECoG monitoring in 20% of patients. Although seizures alone did not influence 6-month functional outcomes in this cohort, they were independently associated with electrographic worsening and a lack of motor improvement following surgery. Temporal interactions between ECoG-detected seizures and SDs were common and held prognostic implications. Together, seizures and SDs may occur along a dynamic continuum of factors critical to the development of secondary brain injury. ECoG provides information integral to the clinical management of patients with TBI.

Electrocorticography During Deep Brain Stimulation Surgery: Safety Experience From 4 Centers Within the National Institute of Neurological Disorders and Stroke Research Opportunities in Human Consortium.

BACKGROUND: Intraoperative research during deep brain stimulation (DBS) surgery has enabled major advances in understanding movement disorders pathophysiology and potential mechanisms for therapeutic benefit. In particular, over the last decade, recording electrocorticography (ECoG) from the cortical surface, simultaneously with subcortical recordings, has become an important research tool for assessing basal ganglia-thalamocortical circuit physiology. OBJECTIVE: To provide confirmation of the safety of performing ECoG during DBS surgery, using data from centers involved in 2 BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative-funded basic human neuroscience projects. METHODS: Data were collected separately at 4 centers. The primary endpoint was complication rate, defined as any intraoperative event, infection, or postoperative magnetic resonance imaging abnormality requiring clinical follow-up. Complication rates for explanatory variables were compared using point biserial correlations and Fisher exact tests. RESULTS: A total of 367 DBS surgeries involving ECoG were reviewed. No cortical hemorrhages were observed. Seven complications occurred: 4 intraparenchymal hemorrhages and 3 infections (complication rate of 1.91%; CI = 0.77%-3.89%). The placement of 2 separate ECoG research electrodes through a single burr hole (84 cases) did not result in a significantly different rate of complications, compared to placement of a single electrode (3.6% vs 1.5%; P = .4). Research data were obtained successfully in 350 surgeries (95.4%). CONCLUSION: Combined with the single report previously available, which described no ECoG-related complications in a single-center cohort of 200 cases, these findings suggest that research ECOG during DBS surgery did not significantly alter complication rates.

Neuro-inflammatory Sequelae of Minimal Trauma in the Non-traumatized Human Brain: A Microdialysis Study.

Cytokine measurement directly from the brain parenchyma by means of microdialysis has documented the activation of certain procedures in vivo, after brain trauma in humans. However, the intercalation of the micro-catheter insertion with the phenomena triggered by the head trauma renders the assessment of the findings problematic. The present study attempts to elucidate the pure effect of minimal trauma, represented by the insertion of the micro-catheter, on the non-traumatized human brain. Microdialysis catheters were implanted in 12 patients with drug-resistant epilepsy, and subjected to invasive electroencephalography with intracranial electrodes. Samples were collected during the first 5 days of monitoring. The dialysate was analyzed using bead flow cytometry, and the concentrations of interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) were measured. The levels of IL-1 and IL-8 were found to be raised until 48 h post-implantation, and thereafter they reached a plateau of presumably baseline values. The temporal profile of the IL-6 variation was different, with the increase being much more prolonged, as its concentration had not returned to baseline levels at the fifth day post-insertion. TNF-α was found to be significantly raised only 2 h after implantation. IL-10 and IL-12 did not have any significant response to micro-trauma. These findings imply that the reaction of the neuro-inflammatory mechanisms of the brain exist even after minimal trauma, and is unexpectedly intense for IL-6. Questions may arise regarding the objectivity of findings attributed by some studies to inflammatory perturbation after head injury.

Utility of invasive electroencephalography in children 3 years old and younger with refractory epilepsy.

OBJECTIVE: Early surgical intervention for pediatric refractory epilepsy is increasingly advocated as surgery has become safer and data have demonstrated improved outcomes with early seizure control. There is concern that the risks associated with staged invasive electroencephalography (EEG) in very young children outweigh the potential benefits. Here, the authors present a cohort of children with refractory epilepsy who were referred for invasive monitoring, and they evaluate the role and safety of staged invasive EEG in those 3 years old and younger. METHODS: The authors conducted a retrospective review of children 3 years and younger with epilepsy, who had been managed surgically at two institutions between 2001 and 2015. A cohort of pediatric patients older than 3 years of age was used for comparison. Demographics, seizure etiology, surgical management, surgical complications, and adverse events were recorded. Statistical analysis was completed using Stata version 13. A p < 0.05 was considered statistically significant. Fisher's exact test was used to compare proportions. RESULTS: Ninety-four patients (45 patients aged ≤ 3 [47.9%]) and 208 procedures were included for analysis. Eighty-six procedures (41.3%) were performed in children younger than 3 years versus 122 in the older cohort (58.7%). Forty-two patients underwent grid placement (14 patients aged ≤ 3 [33.3%]); 3 of them developed complications associated with the implant (3/42 [7.14%]), none of whom were among the younger cohort. Across all procedures, 11 complications occurred in the younger cohort versus 5 in the older patients (11/86 [12.8%] vs 5/122 [4.1%], p = 0.032). Two adverse events occurred in the younger group versus 1 in the older group (2/86 [2.32%] vs 1/122 [0.82%], p = 0.571). Following grid placement, 13/14 younger patients underwent guided resections compared to 20/28 older patients (92.9% vs 71.4%, p = 0.23). CONCLUSIONS: While overall complication rates were higher in the younger cohort, subdural grid placement was not associated with an increased risk of surgical complications in that population. Invasive electrocorticography informs management in very young children with refractory, localization-related epilepsy and should therefore be used when clinically indicated.

Stereoelectroencephalography Versus Subdural Strip Electrode Implantations: Feasibility, Complications, and Outcomes in 500 Intracranial Monitoring Cases for Drug-Resistant Epilepsy.

BACKGROUND: Both stereoelectroencephalography (SEEG) and subdural strip electrodes (SSE) are used for intracranial electroencephalographic recordings in the invasive investigation of patients with drug-resistant epilepsy. OBJECTIVE: To compare SEEG and SSE with respect to feasibility, complications, and outcome in this single-center study. METHODS: Patient characteristics, periprocedural parameters, complications, and outcome were acquired from a pro- and retrospectively managed databank to compare SEEG and SSE cases. RESULTS: A total of 500 intracranial electroencephalographic monitoring cases in 450 patients were analyzed (145 SEEG and 355 SSE). Both groups were of similar age, gender distribution, and duration of epilepsy. Implantation of each SEEG electrode took 13.9 ± 7.6 min (20 ± 12 min for each SSE; P < .01). Radiation exposure to the patient was 4.3 ± 7.7 s to a dose area product of 14.6 ± 27.9 rad*cm2 for SEEG and 9.4 ± 8.9 s with 21 ± 22.4 rad*cm2 for SSE (P < .01). There was no difference in the length of stay (12.2 ± 7.2 and 12 ± 6.3 d). The complication rate was low in both groups. No infections were seen in SEEG cases (2.3% after SSE). The rate of hemorrhage was 2.8% for SEEG and 1.4% for SSE. Surgical outcome was similar. CONCLUSION: SEEG allows targeting deeply situated foci with a non-inferior safety profile to SSE and seizure outcome comparable to SSE.

Analysis of risk factors and clinical sequelae of direct electrical cortical stimulation-induced seizures and afterdischarges in patients undergoing awake mapping.

OBJECTIVE: Intraoperative stimulation has emerged as a crucial adjunct in neurosurgical oncology, aiding maximal tumor resection while preserving sensorimotor and language function. Despite increasing use in clinical practice of this stimulation, there are limited data on both intraoperative seizure (IS) frequency and the presence of afterdischarges (ADs) in patients undergoing such procedures. The objective of this study was to determine risk factors for IS or ADs, and to determine the clinical consequences of these intraoperative events. METHODS: A retrospective chart review was performed for patients undergoing awake craniotomy (both first time and repeat) at a single institution from 2013 to 2018. Hypothesized risk factors for ADs/ISs in patients were evaluated for their effect on ADs and ISs, including tumor location, tumor grade (I-IV), genetic markers (isocitrate dehydrogenase 1/2, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation, chromosome 1p/19q codeletion), tumor volume, preoperative seizure status (yes/no), and dosage of preoperative antiepileptic drugs for each patient. Clinical outcomes assessed in patients with IS or ADs were duration of surgery, length of stay, presence of perioperative deficits, and postoperative seizures. Chi-square analysis was performed for binary categorical variables, and a Student t-test was used to assess continuous variables. RESULTS: A total of 229 consecutive patients were included in the analysis. Thirty-five patients (15%) experienced ISs. Thirteen (37%) of these 35 patients had experienced seizures that were appreciated clinically and noted on electrocorticography simultaneously, while 8 patients (23%) experienced ISs that were electrographic alone (no obvious clinical change). MGMT promoter methylation was associated with an increased prevalence of ISs (OR 3.3, 95% CI 1.2-7.8, p = 0.02). Forty patients (18%) experienced ADs. Twenty-three percent of patients (9/40) with ISs had ADs prior to their seizure, although ISs and ADs were not statistically associated (p = 0.16). The presence of ADs appeared to be correlated with a shorter length of stay (5.1 ± 2.6 vs 6.1 ± 3.7 days, p = 0.037). Of the clinical features assessed, none were found to be predictive of ADs. Neither IS nor AD, or the presence of either IS or AD (65/229 patients), was a predictor for increased length of stay, presence of perioperative deficits, or postoperative seizures. CONCLUSIONS: ISs and ADs, while commonly observed during intraoperative stimulation for brain mapping, do not negatively affect patient outcomes.

A rat model for assessing the long-term safety and performance of peripheral nerve electrode arrays.

BACKGROUND: High-resolution peripheral nerve interfaces (PNIs) can provide amputees with intuitive motor control and sensory feedback. Current PNIs are limited by early device failure and suboptimal long-term stability. The present study aims to incorporate functional assessment into an in vivo test platform to assess the long-term safety and performance of PNIs for recording and stimulation. NEW METHODS: Utah electrode arrays (EA) were implanted in the rat sciatic nerve along with electromyography wires in the gastrocnemius and tibialis anterior. Cranial EEG screws were implanted in the somatosensory cortex for 12 weeks. Spontaneous neural activity was recorded using the implanted EA and stimulation-induced activity was monitored throughout the experiment. The impedance of each electrode was measured, and nerve function tests were conducted throughout the EA lifetime. Post-hoc safety assessments included scanning electron microscopy (SEM) of the EA and nerve histomorphometric analysis. RESULTS: EA recordings were stable, and stimulation with EA elicited somatosensory evoked potentials and muscle contractions. Motor and sensory function tests indicated minimal deficits. Histomorphometric analysis indicated changes in nerve microstructure. SEM indicated EA-tip fracture, while lead wire breakage primarily caused device failure. COMPARISON WITH EXISTING METHODS: We improved our prior platform with the addition of functional assessments of sensory pathways, a robust EMG array design to increase device longevity, and quantitative analysis of nerve microstructure. CONCLUSION: We present a test platform for long-term assessment of peripheral nerve interfaces for stimulation and recording. Using this platform, we demonstrate recording and stimulation with minimal impact on nerve function, while EA lead wire breakage and tip fracture could limit long-term device use.

Risk of seizures induced by intracranial research stimulation: analysis of 770 stimulation sessions.

OBJECTIVE: Patients with medically refractory epilepsy often undergo intracranial electroencephalography (iEEG) monitoring to identify a seizure focus and determine their candidacy for surgical intervention. This clinically necessary monitoring period provides an increasingly utilized research opportunity to study human neurophysiology, however ethical concerns demand a thorough appreciation of the associated risks. We measured the incidence of research stimulation-associated seizures in a large multi-institutional dataset in order to determine whether brain stimulation was statistically associated with seizure incidence and identify potential risk factors for stimulation-associated seizures. APPROACH: 188 subjects undergoing iEEG monitoring across ten institutions participated in 770 research stimulation sessions over 3.5 yr. Seizures within 30 min of a stimulation session were included in our retrospective analysis. We analyzed stimulation parameters, seizure incidence, and typical seizure patterns, to assess the likelihood that recorded seizures were stimulation-induced, rather than events that occurred by chance in epilepsy patients prone to seizing. MAIN RESULTS: In total, 14 seizures were included in our analysis. All events were single seizures, and no adverse events occurred. The mean amplitude of seizure-associated stimulation did not differ significantly from the mean amplitude delivered in sessions without seizures. In order to determine the likelihood that seizures were stimulation induced, we used three sets of analyses: visual iEEG analysis, statistical frequency, and power analyses. We determined that three of the 14 seizures were likely stimulation-induced, five were possibly stimulation-induced, and six were unlikely stimulation-induced. Overall, we estimate a rate of stimulation-induced seizures between 0.39% and 1.82% of sessions. SIGNIFICANCE: The rarity of stimulation-associated seizures and the fact that none added morbidity or affected the clinical course of any patient are important findings for understanding the feasibility and safety of intracranial stimulation for research purposes.

Standard Free Versus Osteoplastic Craniotomy: Assessment of Complication Rates During Intracranial Electroencephalogram Electrode Placement for Seizure Localization.

OBJECTIVE: Patients with medically intractable epilepsy often undergo sequential surgeries and are therefore exposed to an elevated risk for infection, resulting in unanticipated returns to the operating room. The goal of our study was to determine whether use of an osteoplastic bone flap technique would reduce the infection rate in these patients. METHODS: A single-institution, retrospective chart review of patients with medically intractable epilepsy for grid placement was performed. Univariate analyses and linear regression were used to assess primary outcomes, including infection and hematomas requiring surgical evacuation. Secondary outcomes included duration of treatment and other, unanticipated surgeries. RESULTS: A total of 199 patients were identified, 56 (28%) with osteoplastic flaps. Standard free flaps were associated with an increased rate of infection at the craniotomy site (n = 24, 17%, vs. 0, 0%, P = 0.003), whereas osteoplastic flaps were associated with more returns to operating room for hematoma evacuation (n = 5, 9% vs. 3.2%, P = 0.024). Overall, the rate of return to operating room for unanticipated surgeries was similar, but infectious complications prolonged the duration of treatment (median: 17 days vs. 2 days, χ2 = 13.97, P < 0.001). CONCLUSIONS: Osteoplastic bone flaps markedly decreased the risk of craniotomy infections compared with free flaps in patients undergoing sequential surgeries. This decrease is offset, however, by an increase in intracranial hematoma requiring return to the operating room. Infection appeared to be a more significant complication as it was associated with increased duration of treatment. The osteoplastic technique is especially appealing in those patients likely to undergo multiple surgeries in short succession.

Utility and safety of depth electrodes within the supratemporal plane for intracranial EEG.

OBJECTIVE: The epileptogenic zones in some patients with temporal lobe epilepsy (TLE) involve regions outside the typical extent of anterior temporal lobectomy (i.e., "temporal plus epilepsy"), including portions of the supratemporal plane (STP). Failure to identify this subset of patients and adjust the surgical plan accordingly results in suboptimum surgical outcomes. There are unique technical challenges associated with obtaining recordings from the STP. The authors sought to examine the clinical utility and safety of placing depth electrodes within the STP in patients with TLE. METHODS: This study is a retrospective review and analysis of all cases in which patients underwent intracranial electroencephalography (iEEG) with use of at least one STP depth electrode over the 10 years from January 2006 through December 2015 at University of Iowa Hospitals and Clinics. Basic clinical information was collected, including the presence of ictal auditory symptoms, electrode coverage, monitoring results, resection extent, outcomes, and complications. Additionally, cases in which the temporal lobe was primarily or secondarily involved in seizure onset and propagation were categorized based upon how rapidly epileptic activity was observed within the STP following seizure onsets: within 1 second, between 1 and 15 seconds, after 15 seconds, and not involved. RESULTS: Fifty-two patients underwent iEEG with STP coverage, with 1 STP electrode used in 45 (86.5%) cases and 2 STP electrodes in the other cases. There were no complications related to STP electrode placement. Of 42 cases in which the temporal lobe was primarily or secondarily involved, seizure activity was recorded from the STP in 36 cases (85.7%): in 5 cases (11.9%) within 1 second, in 5 (11.9%) between 1 and 15 seconds, and in 26 (61.9%) more than 15 seconds following seizure onset. Seizure outcomes inversely correlated with rapid ictal involvement of the STP (Engel class I achieved in 25%, 67%, and 82% of patients in the above categories, respectively). All patients without ictal STP involvement achieved seizure freedom. Only 4 (11.1%) patients with STP ictal involvement reported auditory symptoms. CONCLUSIONS: Ictal involvement of the STP is common even in the absence of auditory symptoms and can be effectively detected by the STP electrodes. These electrodes are safe to implant and provide useful prognostic information.

Delayed high-frequency suppression after automated single-pulse electrical stimulation identifies the seizure onset zone in patients with refractory epilepsy.

OBJECTIVE: Single-pulse electrical stimulation (SPES) of intracranial electrodes evokes responses that may help identify the seizure onset zone (SOZ); however, lack of automation and response variability has limited clinical adoption of this technique. We evaluated whether automated delivery of low-current SPES could evoke delayed high-frequency suppression (DHFS) of ongoing electrocorticography (ECoG) signals that, when combined with objective analytic techniques, may provide a reliable marker of this zone. METHODS: Low-current SPES (1-ms, 3.5-mA biphasic pulses) was delivered to 652 electrodes across 10 patients undergoing ECoG for seizure focus localization. DHFS was measured by calculating the normalized trial-averaged time-frequency power (70-250 Hz) 0.4-1 sec post-stimulation. Electrodes that evoked suppression when stimulated or recorded suppression when stimulation was nearby were used to estimate the SOZ. RESULTS: The estimated SOZ significantly identified the clinical SOZ in 6 of 10 patients (5 of 7 temporal foci) with a false-positive rate of 0-0.06. Stimulation required <2 h, was undetectable by patients, and did not induce seizures or after-discharges. CONCLUSIONS: We show that DHFS provides accurate estimates of the clinical SOZ in patients with refractory epilepsy. SIGNIFICANCE: This approach may increase the safety, speed, and reproducibility of SOZ identification while reducing cost, subjectivity, and patient discomfort.

Language and motor function thresholds during pediatric extra-operative electrical cortical stimulation brain mapping.

OBJECTIVE: To examine current thresholds and their determinants for language and motor mapping with extra-operative electrical cortical stimulation (ECS). METHODS: ECS electrocorticograph recordings were reviewed to determine functional thresholds. Predictors of functional thresholds were found with multivariable analyses. RESULTS: In 122 patients (age 11.9±5.4years), average minimum, frontal, and temporal language thresholds were 7.4 (± 3.0), 7.8 (± 3.0), and 7.4 (± 3.1) mA respectively. Average minimum, face, upper and lower extremity motor thresholds were 5.4 (± 2.8), 6.1 (± 2.8), 4.9 (± 2.3), and 5.3 (± 3.3) mA respectively. Functional and after-discharge (AD)/seizure thresholds were significantly related. Minimum, frontal, and temporal language thresholds were higher than AD thresholds at all ages. Minimum motor threshold was higher than minimum AD threshold up to 8.0years of age, face motor threshold was higher than frontal AD threshold up to 11.8years age, and lower subsequently. UE motor thresholds remained below frontal AD thresholds throughout the age range. CONCLUSIONS: Functional thresholds are frequently above AD thresholds in younger children. SIGNIFICANCE: These findings raise concerns about safety and neurophysiologic validity of ECS mapping. Functional and AD/seizure thresholds relationships suggest individual differences in cortical excitability which cannot be explained by clinical variables.

After-discharges and seizures during pediatric extra-operative electrical cortical stimulation functional brain mapping: Incidence, thresholds, and determinants.

OBJECTIVE: This study examined the incidence, thresholds, and determinants of electrical cortical stimulation (ECS)-induced after-discharges (ADs) and seizures. METHODS: Electrocorticograph recordings were reviewed to determine incidence of ECS-induced ADs and seizures. Multivariable analyses for predictors of AD/seizure occurrence and their thresholds were performed. RESULTS: In 122 patients, the incidence of ADs and seizures was 77% (94/122) and 35% (43/122) respectively. Males (odds ratio [OR] 2.92, 95% CI 1.21-7.38, p=0.02) and MRI-negative patients (OR 3.69, 95% CI 1.24-13.7, p=0.03) were found to have higher odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient -0.151, 95% CI -0.267 to -0.035, p=0.011). ECS-induced seizures were more likely in patients with lateralized functional imaging (OR 6.62, 95% CI 1.36-55.56, p=0.036, for positron emission tomography) and presence of ADs (OR 3.50, 95% CI 1.12-13.36, p=0.043). CONCLUSIONS: ECS is associated with a high incidence of ADs and seizures. With age, current thresholds decrease and the probability for AD/seizure occurrence increases. SIGNIFICANCE: ADs and seizures during ECS brain mapping are potentially hazardous and affect its functional validity. Thus, safer method(s) for brain mapping with improved neurophysiologic validity are desirable.

Decision analysis of intracranial monitoring in non-lesional epilepsy.

PURPOSE: Up to one third of epilepsy patients develop pharmacoresistant seizures and many benefit from resective surgery. However, patients with non-lesional focal epilepsy often require intracranial monitoring to localize the seizure focus. Intracranial monitoring carries operative morbidity risk and does not always succeed in localizing the seizures, making the benefit of this approach less certain. We performed a decision analysis comparing three strategies for patients with non-lesional focal epilepsy: (1) intracranial monitoring, (2) vagal nerve stimulator (VNS) implantation and (3) medical management to determine which strategy maximizes the expected quality-adjusted life years (QALYs) for our base cases. METHOD: We constructed two base cases using parameters reported in the medical literature: (1) a young, otherwise healthy patient and (2) an elderly, otherwise healthy patient. We constructed a decision tree comprising strategies for the treatment of non-lesional epilepsy and two clinical outcomes: seizure freedom and no seizure freedom. Sensitivity analyses of probabilities at each branch were guided by data from the medical literature to define decision thresholds across plausible parameter ranges. RESULTS: Intracranial monitoring maximizes the expected QALYs for both base cases. The sensitivity analyses provide estimates of the values of key variables, such as the surgical risk or the chance of localizing the focus, at which intracranial monitoring is no longer favored. CONCLUSION: Intracranial monitoring is favored over VNS and medical management in young and elderly patients over a wide, clinically-relevant range of pertinent model variables such as the chance of localizing the seizure focus and the surgical morbidity rate.

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate.

OBJECTIVE: Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. APPROACH: We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. MAIN RESULTS: Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. SIGNIFICANCE: These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.

Complications in Aneurysmal Subarachnoid Hemorrhage Patients With and Without Subdural Electrode Strip for Electrocorticography.

PURPOSE: Patients with aneurysmal subarachnoid hemorrhage (aSAH) frequently develop secondary noninfectious and infectious complications with an important impact on clinical course and outcome. In this study, we report on the rate of typical extracranial and intracranial complications in 30 prospectively enrolled patients with severe aSAH who received a linear subdural recording strip for continuous electrocorticography to detect ictal epileptiform events and spreading depolarizations. METHODS: The group was compared with 30 retrospectively included patients with aSAH who had not received a subdural recording strip, but were treated during the same period. The control group was matched according to an aSAH grading system, sex, and establishment of external ventricular drainage, but could not be matched according to aneurysm treatment and focal brain lesions such as initial intracerebral hemorrhages. RESULTS: No evidence was found that procedures of the electrocorticography study led to clinically relevant complications. In particular, the subdural strip did not lead to local damage of brain tissue or any increased rate of meningitis/ventriculitis. The median score on the modified Rankin Scale on day 15 was the same in both groups. Minor differences between both groups are explained by the limitations in the study design. CONCLUSIONS: Our study suggests that neuromonitoring with a subdural recording strip for up to 15 days can be safely performed in patients with aSAH.

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.

Comparison of computer-assisted planning and manual planning for depth electrode implantations in epilepsy.

OBJECT The objective of this study was to evaluate the clinical utility of multitrajectory computer-assisted planning software (CAP) to plan stereoelectroencephalography (SEEG) electrode arrangements. METHODS A cohort of 18 patients underwent SEEG for evaluation of epilepsy at a single center between August 2013 and August 2014. Planning of electrodes was performed manually and stored using EpiNav software. CAP was developed as a planning tool in EpiNav. The user preselects a set of cerebral targets and optimized trajectory constraints, and then runs an automated search of potential scalp entry points and associated trajectories. Each trajectory is associated with metrics for a safety profile, derived from the minimal distance to vascular structures, and an efficacy profile, derived from the proportion of depth electrodes that are within or adjacent to gray matter. CAP was applied to the cerebral targets used in the cohort of 18 previous manually planned implantations to generate new multitrajectory implantation plans. A comparison was then undertaken for trajectory safety and efficacy. RESULTS CAP was applied to 166 electrode targets in 18 patients. There were significant improvements in both the safety profile and efficacy profile of trajectories generated by CAP compared with manual planning (p < 0.05). Three independent neurosurgeons assessed the feasibility of the trajectories generated by CAP, with 131 (78.9%) of 166 trajectories deemed suitable for implementation in clinical practice. CAP was performed in real time, with a median duration of 8 minutes for each patient, although this does not include the time taken for data preparation. CONCLUSIONS CAP is a promising tool to plan SEEG implantations. CAP provides feasible depth electrode arrangements, with quantitatively greater safety and efficacy profiles, and with a substantial reduction in duration of planning within the 3D multimodality framework.

National trends and complication rates for invasive extraoperative electrocorticography in the USA.

Invasive electrocorticography (ECoG) is used in patients when it is difficult to localize epileptogenic foci for potential surgical resection. As MR neuroimaging has improved over the past decade, we hypothesized the utilization of ECoG diminishing over time. Using the USA Nationwide Inpatient Sample, we collected demographic and complication data on patients receiving ECoG over the years 1988-2008 and compared this to patients with medically refractory epilepsy during the same time period. A total of 695 cases using extraoperative ECoG were identified, corresponding to 3528 cases nationwide and accounting for 1.1% of patients with refractory epilepsy from 1988-2008. African Americans were less likely to receive ECoG than whites, as were patients with government insurance in comparison to those with private insurance. Large, urban, and academic hospitals were significantly more likely to perform ECoG than smaller, rural, and private practice institutions. The most frequent complication was cerebrospinal fluid leak (11.7%) and only one death was reported from the entire cohort, corresponding to an estimated six patients nationally. Invasive ECoG is a relatively safe procedure offered to a growing number of patients with refractory epilepsy each year. However, these data suggest the presence of demographic disparities in those patients receiving ECoG, possibly reflecting barriers due to race and socioeconomic status. Among patients with nonlocalized seizures, ECoG often represents their only hope for surgical treatment. We therefore must further examine the indications and efficacy of ECoG, and more work must be done to understand if and why ECoG is preferentially performed in select socioeconomic groups.