Seizure Onset Area Research Articles

Oscillatory and nonoscillatory sleep electroencephalographic biomarkers of the epileptic network.

In addition to the oscillatory brain activity, the nonoscillatory (scale-free) components of the background electroencephalogram (EEG) may provide further information about the complexity of the underlying neuronal network. As epilepsy is considered a network disease, such scale-free metrics might help to delineate the epileptic network. Here, we performed an analysis of the sleep oscillatory (spindle, slow wave, and rhythmic spectral power) and nonoscillatory (H exponent) intracranial EEG using multiple interictal features to estimate whether and how they deviate from normalcy in 38 adults with drug-resistant epilepsy. To quantify intracranial EEG abnormalities within and outside the seizure onset areas, patients' values were adjusted based on normative maps derived from the open-access Montreal Neurological Institute open iEEG Atlas. In a subset of 29 patients who underwent resective surgery, we estimated the predictive value of these features to identify the epileptogenic zone in those with a good postsurgical outcome. We found that distinct sleep oscillatory and nonoscillatory metrics behave differently across the epileptic network, with the strongest differences observed for (1) a reduction in spindle activity (spindle rates and rhythmic sigma power in the 10-16 Hz band), (2) a higher rhythmic gamma power (30-80 Hz), and (3) a higher H exponent (steeper 1/f slope). As expected, epileptic spikes were also highest in the seizure onset areas. Furthermore, in surgical patients, the H exponent achieved the highest performance (balanced accuracy of .76) for classifying resected versus nonresected channels in good outcome patients. This work suggests that nonoscillatory components of the intracranial EEG signal could serve as promising interictal sleep candidates of epileptogenicity in patients with drug-resistant epilepsy. Our findings further advance the understanding of epilepsy as a disease, whereby absence or loss of sleep physiology may provide information complementary to pathological epileptic processes.

Diagnostic value of high frequency oscillation in localization of type Ⅱ focal cortical dysplasia epilepsy

Retrospective analysis was conducted on 9 patients with type Ⅱ focal cortical dysplasia (FCD) who underwent stereo-electroencephalography (SEEG) implantation in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University from November 2020 to February 2023. The onset area, onset time, and frequency of high-frequency oscillations (HFO) were analyzed and the correlation of HFOs with interictal, preictal, and ictal periods. SEEG recordings of 80-500 Hz HFOs were observed in both interictal and ictal periods in 9 patients, with 6 patients exhibiting fast ripples (FR) in the range of 250-500 Hz. Surgical resection of the seizure onset area and FR-generating electrodes was performed, and postoperative follow-up for over 2 years indicated Engel I in 5 cases. 6 patients showed continuous discharge during the preictal period, and the distribution index of continuous discharge was positively correlated with seizure frequency. HFOs in the range of 80-500 Hz were present in all four seizure onset patterns during the ictal period. The onset area and FR-emitting electrode were surgically removed in 6 patients with continuous discharge and overlapping HFOs during the preictal period, with 5 cases of Engel I. Type Ⅱ FCD discharges exhibited complexity, high discharge indices, and a close association with HFOs. Compared with the spike wave, the electrode range of HF is more limited, and the incidence of HF before attack is significantly increased, which is closely correlated with the onset area. The simultaneous occurrence of HFO and the spike waves has higher diagnostic value than the individual occurrence, effectively enhancing surgical efficacy.

Electrocorticography Recorded from Subdural Electrodes and Stereo-Electroencephalography

Epilepsy surgeons often encounter drug-resistant focal epilepsy, which needs to be diagnosed so that the epileptic foci can be identified and the patient treated. When noninvasive preoperative evaluation cannot determine the region of seizure onset or eloquent cortical areas, invasive epileptic video-EEG monitoring using intracranial electrodes needs to be applied. While subdural electrodes have been used to accurately identify epileptogenic foci via electrocorticography for some time, the use of stereo-electroencephalography has recently exploded in Japan, due to its less invasive nature and its better ability to reveal epileptogenic networks. This report describes the underlying concepts, indications, procedures, and contributions to neuroscience of both surgical procedures.

In vitro ictogenesis is stochastic at the single neuron level.

Seizure initiation is the least understood and most disabling element of epilepsy. Studies of ictogenesis require high speed recordings at cellular resolution in the area of seizure onset. However, in vivo seizure onset areas cannot be determined at the level of resolution necessary to enable such studies. To circumvent these challenges, we used novel GCaMP7-based calcium imaging in the organotypic hippocampal slice culture model of post-traumatic epilepsy in mice. Organotypic hippocampal slice cultures generate spontaneous, recurrent seizures in a preparation in which it is feasible to image the activity of the entire network (with no unseen inputs existing). Chronic calcium imaging of the entire hippocampal network, with paired electrophysiology, revealed three patterns of seizure onset: (i) low amplitude fast activity; (ii) sentinel spike; and (iii) spike burst and low amplitude fast activity onset. These patterns recapitulate common features of human seizure onset, including low voltage fast activity and spike discharges. Weeks-long imaging of seizure activity showed a characteristic evolution in onset type and a refinement of the seizure onset zone. Longitudinal tracking of individual neurons revealed that seizure onset is stochastic at the single neuron level, suggesting that seizure initiation activates neurons in non-stereotyped sequences seizure to seizure. This study demonstrates for the first time that transitions to seizure are not initiated by a small number of neuronal 'bad actors' (such as overly connected hub cells), but rather by network changes which enable the onset of pathology among large populations of neurons.

Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data.

ObjectiveTo compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans.MethodsWe developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI‐visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG.ResultsSeizure‐onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG.SignificanceComputational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co‐located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery.

Physiological Ripples Associated With Sleep Spindles Can Be Identified in Patients With Refractory Epilepsy Beyond Mesio-Temporal Structures.

Introduction: High frequency oscillations (HFO) are promising biomarkers of epileptic tissue. While group analysis suggested a correlation between surgical removal of HFO generating tissue and seizure free outcome, HFO could not predict seizure outcome on an individual patient level. One possible explanation is the lack of differentiation between physiological and epileptic HFO. In the mesio-temporal lobe, a proportion of physiological ripples can be identified by their association with scalp sleep spindles. Spike associated ripples in contrast can be considered epileptic. This study investigated whether categorizing ripples by the co-occurrence with sleep spindles or spikes improves outcome prediction after surgery. Additionally, it aimed to investigate whether spindle-ripple association is limited to the mesio-temporal lobe structures or visible across the whole brain.Methods: We retrospectively analyzed EEG of 31 patients with chronic intracranial EEG. Sleep spindles in scalp EEG and ripples and epileptic spikes in iEEG were automatically detected. Three ripple subtypes were obtained: SpindleR, Non-SpindleR, and SpikeR. Rate ratios between removed and non-removed brain areas were calculated. We compared the distinct ripple subtypes and their rates in different brain regions, inside and outside seizure onset areas and between patients with good and poor seizure outcome.Results: SpindleR were found across all brain regions. SpikeR had significantly higher rates in the SOZ than in Non-SOZ channels. A significant positive correlation between removal of ripple-events and good outcome was found for the mixed ripple group (rs = 0.43, p = 0.017) and for ripples not associated with spindles (rs=0.40, p = 0.044). Also, a significantly high proportion of spikes associated with ripples were removed in seizure free patients (p = 0.036).Discussion: SpindleR are found in mesio-temporal and neocortical structures, indicating that ripple-spindle-coupling might have functional importance beyond mesio-temporal structures. Overall, the proportion of SpindleR was low and separating spindle and spike associated ripples did not improve outcome prediction in our patient group. SpindleR analysis therefore can be a tool to identify physiological events but needs to be used in combination with other methods to have clinical relevance.

Network radiofrequency ablation for drug resistant epilepsy.

Radiofrequency ablation (RFA) is a minimally invasive procedure for drug-resistant focal epilepsy. Although well tolerated, seizure outcomes are less favorable than standard resection. RFA is commonly performed following stereoencephalography (sEEG) identification of the seizure onset zone (SOZ). We hypothesized RFA outcomes can improve by adding RFA of seizure spread regions to the SOZ as identified by sEEG, an approach we term network RFA. Four patients underwent network RFA at our institution from 8/2017 to 9/2019. There were two Engel IB outcomes and two Engel III outcomes. The median follow-up length was 25.5months (range 17-35). No permanent neurological deficits occurred. Etiologies consisted of polymicrogyria (1), mixed malformation of cortical development (MCD) (2), and cryptogenic (1). This study provides descriptive results regarding the efficacy and safety of network RFA. Network RFA can be considered in patients with focal epilepsies with large MCDs that may not be amenable to standard resection.

Effectively combining temporal projection noise suppression methods in magnetoencephalography

BackgroundMagnetoencephalography (MEG) is an excellent non-invasive tool to study the brain. However, measurements often suffer from the contribution of external interference, including noise from the sensors. Suppression of noise from the data is critical for an accurate representation of brain signals. Due to MEG’s limited spatial resolution and superior temporal resolution, noise suppression methods that operate in the temporal domain can be favorable. New MethodWe examined the independent and joint effects of two temporal projection noise suppression algorithms for MEG measurements: One commonly used algorithm which suppresses correlated noise; temporal signal space separation (tSSS) and one new method which suppresses uncorrelated sensor noise; oversampled temporal projection (OTP). ResultsWe found that both OTP and tSSS effectively suppress noise in raw MEG data and have the greatest effect of joint operation in cases where SNR is low, or when detecting higher SNR single-trial responses from raw data. We additionally demonstrate how the combination of OTP and tSSS is useful for the detectability of high-frequency brain oscillations (HFO). Comparison with existing MethodsAlthough the mathematical description of OTP has been described before (Larson and Taulu, 2017), OTP’s effect on HFOs in MEG data is novel. Additionally, the combination of OTP and commonly used temporal noise suppression algorithms (i.e., tSSS) has not been shown. ConclusionsThis finding is applicable to clinical populations such as epilepsy, where HFO signals are thought to be important markers for areas of seizure onset and are typically difficult to detect with non-invasive neuroimaging methods.

Circadian-Like Rhythmicity of Extracellular Brain Glutamate in Epilepsy.

Seizures often exhibit striking circadian-like (~24-h) rhythms. While chronotherapy has shown promise in treating epilepsy, it is not widely used, in part because the patterns of seizure rhythmicity vary considerably among patients and types of epilepsy. A better understanding of the mechanisms underlying rhythmicity in epilepsy could be expected to result in more effective approaches which can be tailored to each individual patient. The excitatory neurotransmitter glutamate is an essential modulator of circadian rhythms, and changes in the extracellular levels of glutamate likely affect the threshold to seizures. We used a reverse translational rodent model of mesial temporal lobe epilepsy (MTLE) combined with long-term intracerebral microdialysis to monitor the hourly concentrations of glutamate in the seizure onset area (epileptogenic hippocampus) over several days. We observed significant 24-h oscillations of extracellular glutamate in the epileptogenic hippocampus (n = 4, JTK_CYCLE test, p < 0.05), but not in the hippocampus of control animals (n = 4). To our knowledge, circadian glutamate oscillations have not been observed in a seizure onset region, and we speculate that the oscillations contribute to the rhythmicity of seizures in MTLE.

The fence post depth electrode technique to control both brain tumors and epileptic seizures in patients with brain tumor-related epilepsy.

Background:To control brain tumor-related epilepsy (BTRE), both epileptological and neuro-oncological approaches are required. We hypothesized that using depth electrodes (DEs) as fence post catheters, we could detect the area of epileptic seizure onset and achieve both brain tumor removal and epileptic seizure control.Methods:Between August 2009 and April 2018, we performed brain tumor removal for 27 patients with BTRE. Patients who underwent lesionectomy without DEs were classified into Group 1 (13 patients) and patients who underwent the fence post DE technique were classified into Group 2 (14 patients).Results:The patients were 15 women and 12 men (mean age, 28.1 years; median age 21 years; range, 5–68 years). The brain tumor was resected to a greater extent in Group 2 than Group 1 (P < 0.001). Shallower contacts showed more epileptogenicity than deeper contacts (P < 0.001). Group 2 showed better epilepsy surgical outcomes than Group 1 (P = 0.041).Conclusion:Using DEs as fence post catheters, we detected the area of epileptic seizure onset and controlled epileptic seizures. Simultaneously, we removed the brain tumor to a greater extent with fence post DEs than without.

Intracortical neural activity distal to seizure-onset-areas predicts human focal seizures.

The apparent unpredictability of epileptic seizures has a major impact in the quality of life of people with pharmacologically resistant seizures. Here, we present initial results and a proof-of-concept of how focal seizures can be predicted early in advance based on intracortical signals recorded from small neocortical patches away from identified seizure onset areas. We show that machine learning algorithms can discriminate between interictal and preictal periods based on multiunit activity (i.e. thresholded action potential counts) and multi-frequency band local field potentials recorded via 4 X 4 mm2 microelectrode arrays. Microelectrode arrays were implanted in 5 patients undergoing neuromonitoring for resective surgery. Post-implant analysis revealed arrays were outside the seizure onset areas. Preictal periods were defined as the 1-hour period leading to a seizure. A 5-minute gap between the preictal period and the putative seizure onset was enforced to account for potential errors in the determination of actual seizure onset times. We used extreme gradient boosting and long short-term memory networks for prediction. Prediction accuracy based on the area under the receiver operating characteristic curves reached 90% for at least one feature type in each patient. Importantly, successful prediction could be achieved based exclusively on multiunit activity. This result indicates that preictal activity in the recorded neocortical patches involved not only subthreshold postsynaptic potentials, perhaps driven by the distal seizure onset areas, but also neuronal spiking in distal recurrent neocortical networks. Beyond the commonly identified seizure onset areas, our findings point to the engagement of large-scale neuronal networks in the neural dynamics building up toward a seizure. Our initial results obtained on currently available human intracortical microelectrode array recordings warrant new studies on larger datasets, and open new perspectives for seizure prediction and control by emphasizing the contribution of multiscale neural signals in large-scale neuronal networks.

Seizure susceptibility and infraslow modulatory activity in the intracranial electroencephalogram.

Studies of infraslow amplitude modulations (<0.15Hz) of band power time series suggest that these envelope correlations may form a basis for distant spatial coupling in the brain. In this study, we sought to determine how infraslow relationships are affected by antiepileptic drug (AED) taper, time of day, and seizure. We studied intracranial electroencephalographic (icEEG) data collected from 13 medically refractory adult epilepsy patients who underwent monitoring at Yale-New Haven Hospital. We estimated the magnitude-squared coherence (MSC) at <0.15Hz of traditional EEG frequency band power time series for all electrode contact pairs to quantify infraslow envelope correlations between them. We studied, first, hour-long background icEEG epochs before and after AED taper to understand the effect of taper. Second, we analyzed the entire record for each patient to study the effect of time of day. Finally, for each patient, we reviewed the clinical record to find all seizures that were at least 6hours removed from other seizures and analyzed infraslow envelope MSC before and after them. Infraslow envelope MSC increased slightly, but significantly, after AED taper, and increased on average during the night and decreased during the day. It was also increased significantly in all frequency bands up to 3hours preseizure and 1hour postseizure as compared to background icEEG (61 seizures studied). These changes occurred for both daytime and nighttime seizures (28 daytime, 33 nighttime). Interestingly, there was significant spatial variability to these changes, with the seizure onset area peaking at 3hours preseizure, then showing progressive desynchronization from 3hours preseizure to 1hour postseizure. Infraslow envelope analysis may be used to understand long-term changes over the course of icEEG monitoring, provide unique insight into interictal electrophysiological changes related to ictogenesis, and contribute to the development of novel seizure forecasting algorithms.

Ictal and preictal power changes outside of the seizure focus correlate with seizure generalization.

The treatment of focal epilepsies is largely predicated on the concept that there is a "focus" from which the seizure emanates. Yet, the physiological context that determines if and how ictal activity starts and propagates remains poorly understood. To delineate these phenomena more completely, we studied activity outside the seizure-onset zone prior to and during seizure initiation. Stereotactic depth electrodes were implanted in 17 patients with longstanding pharmacoresistant epilepsy for lateralization and localization of the seizure-onset zone. Only seizures with focal onset in mesial temporal structures were used for analysis. Spectral analyses were used to quantify changes in delta, theta, alpha, beta, gamma, and high gamma frequency power, in regions inside and outside the area of seizure onset during both preictal and seizure initiation periods. In the 78 seizures examined, an average of 9.26% of the electrode contacts outside of the seizure focus demonstrated changes in power at seizure onset. Of interest, seizures that were secondarily generalized, on average, showed power changes in a greater number of extrafocus electrode contacts at seizure onset (16.7%) compared to seizures that remained focal (3.8%). The majority of these extrafocus changes occupied the delta and theta bands in electrodes placed in the ipsilateral, lateral temporal lobe. Preictally, we observed extrafocal high-frequency power decrements, which also correlated with seizure spread. This widespread activity at and prior to the seizure-onset time further extends the notion of the ictogenic focus and its relationship to seizure spread. Further understanding of these extrafocus, periictal changes might help identify the neuronal dynamics underlying the initiation of seizures and how therapies can be devised to control seizure activity.

Predicting the spatiotemporal diversity of seizure propagation and termination in human focal epilepsy

Recent studies have shown that seizures can spread and terminate across brain areas via a rich diversity of spatiotemporal patterns. In particular, while the location of the seizure onset area is usually invariant across seizures in an individual patient, the source of traveling (2–3 Hz) spike-and-wave discharges during seizures can either move with the slower propagating ictal wavefront or remain stationary at the seizure onset area. Furthermore, although many focal seizures terminate synchronously across brain areas, some evolve into distinct ictal clusters and terminate asynchronously. Here, we introduce a unifying perspective based on a new neural field model of epileptic seizure dynamics. Two main mechanisms, the co-existence of wave propagation in excitable media and coupled-oscillator dynamics, together with the interaction of multiple time scales, account for the reported diversity. We confirm our predictions in seizures and tractography data obtained from patients with pharmacologically resistant epilepsy. Our results contribute toward patient-specific seizure modeling.

Inflammation and Epilepsy: Preclinical Findings and Potential Clinical Translation.

The lack of treatments which can prevent epilepsy development or improve disease prognosis represents an unmet and urgent clinical need. The development of such drugs requires a deep understanding of the mechanisms underlying disease pathogenesis. In the last decade, preclinical studies in models of acute seizures and of chronic epilepsy highlighted that neuroinflammation arising in brain areas of seizure onset and generalization is a key contributor to neuronal hyper-excitability underlying seizure generation. Microglia and astrocytes are pivotal cells involved in both the induction and perpetuation of the inflammatory response to epileptogenic injuries or seizures; other cell contributors are neurons, cell components of the blood brain barrier and leukocytes. From the clinical standpoint, neuroinflammation is now considered an hallmark of epileptogenic foci in various forms of focal onset pharmacoresistant epilepsies. Moreover, pharmacological studies in animal model with drugs targeting specific inflammatory molecules, and changes in intrinsic seizure susceptibility of transgenic mice with perturbed neuroinflammatory mechanisms, have demonstrated that neuroinflammation is not a bystander phenomenon but has a pathogenic role in seizures, cell loss and neurological co-morbidities. Understanding the role of neuroinflammation in seizure pathogenesis is instrumental for a mechanism-based discovery of selective therapies targeting the epilepsy causes rather than its symptoms, thereby allowing the development of novel disease-modifying treatments. Notably, clinical translation of laboratory findings may take advantage of anti-inflammatory drugs already in medical use for peripheral autoinflammatory or autoimmune disorders. This review reports key preclinical and clinical findings supporting a role for brain inflammation in the pathogenesis of seizures. It also highlights the emerging proof-of-concept studies showing signs of clinical efficacy of target-specific anti-inflammatory interventions in epilepsies of differing etiologies. We will discuss the need for biomarkers and novel clinical trial designs for anti-inflammatory therapies that have a mechanism of action very different than standard antiepileptic drugs.

Functional neuroimaging in Rasmussen syndrome

PurposeFor a diagnosis of Rasmussen syndrome (RS), clinical course together with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings are considered important, but there are few reports on functional neuroimaging. This study investigated cerebral blood flow (CBF)-single photon emission computed tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18 fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and correlated neuroimaging results with MRI and pathological findings. MethodsTwenty-three patients diagnosed with RS according to Bien’s (2005) diagnostic criteria (including 12 patients with a histological diagnosis) were studied. CBF-SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings correlated with MRI and histological findings. ResultsHypoperfusion areas were observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine patients, lowered uptake was detected in all nine patients, including two with no MRI abnormalities. Lowered glucose metabolism was observed in affected areas in all five patients by FDG-PET. Histological examination revealed findings of chronic encephalitis in all 12 patients examined, concomitant with focal cortical dysplasia in five patients. ConclusionIn RS patients, functional neuroimaging reveals clear abnormal findings, even before the appearance of MRI abnormalities. BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may suggest possible impairment of inhibitory neurons.

Surgical treatment of epilepsy in patients with mediobasal temporal cavernous malformations

Epilepsy is a frequent clinical manifestation of cavernous malformations (CMs) of the mediobasal temporal region (MBTR). Surgical removal of CMs is an excellent technique for treating associated epilepsy and may range from pure lesionectomy to tailored resection of the temporal lobe. The study purpose was to determine the optimal surgical management for epilepsy in patients with CMs of the MBTR. We retrospectively analyzed the clinical data, neuroimaging findings, surgical techniques, and surgical outcomes in 11 patients with epilepsy and CMs of the MBTR. All patients underwent video-electroencephalography, magnetic resonance imaging, and computed tomography in the pre- and postoperative periods. Nine patients underwent preoperative implantation of foramen ovale electrodes. In all cases, surgery was accompanied by electrocorticography (ECoG). CMs were located in the anterior MBTR in 7 cases, anterior and middle thirds of the MBTR in 1 case, middle third in 2 cases, and middle and posterior thirds in 1 case. In 8 patients, preoperative monitoring revealed a seizure onset area in the MBTR. These patients underwent cavernomectomy with ECoG-guided resection of the hemosiderin ring and adjacent tissue using the pterional (4 cases) or supracerebellar transtentorial approach (4). In 3 cases, anterior temporal lobectomy with cavernomectomy was additionally used due to spreading of pathological activity to the lateral temporal neocortex. Seizure control after surgery was excellent in 7 patients (class 1 ILAE) and good in 4 (class 2 ILAE). Surgery in patients with epilepsy caused by CMs of the MBTR should be performed based on non-invasive and invasive presurgical evaluation. If the seizure onset area is located in the MBTR, lesionectomy with ECoG-guided resection of the adjacent temporal cortical areas can be performed using the pterional or supracerebellar transtentorial approach. Lateral spread of epileptic activity requires cavernomectomy and anterior temporal lobectomy.

Bone flap elevation for intracranial EEG monitoring: technical note.

Intracranial electroencephalography (iEEG) provides invaluable information in determining seizure focus and spread due to its high spatial and temporal resolution, which are not afforded by noninvasive studies. Electrodes of various types (e.g., grid, strip, and depth electrodes) and configurations are often used for optimum coverage of suspected areas of seizure onset and propagation. Given the fixed intracranial volume and added mass effect from placement of cortical electrodes, brain edema and postoperative deficits can occur. The authors describe a simple, inexpensive, and highly effective technique of bone flap replacement using standard titanium plates to expand the intracranial volume and minimize risks of brain compression and intracranial hypertension. Rectangular titanium plates are bent and placed in a way that secures the bone flap in a slightly elevated position relative to the adjacent calvaria during iEEG monitoring. The authors evaluated the degree of bone flap elevation and amount of volume created using this technique in 3 iEEG cases. They then compared these results with the bone flap elevation and volume created using linear titanium plates, a method they had used previously. The use of rectangular plates produced on average 6.6 mm of bone flap elevation, compared with only 1.8 mm of bone flap elevation with the use of linear plates, resulting in a statistically significant 261% increase in bone flap elevation (p ≤ 0.001). The authors suggest that rectangular plates may provide stronger resistance to scalp tension after myocutaneous skin closure compared with the linear plates and that subsidence of the bone flap likely occurred with the use of linear plates. In summary, the described technique utilizing rectangular plates creates significantly increased bone flap elevation compared with a similar method using linear plates, and it may reduce the risk of neurological deficits related to intracranial electrode placement.

Brief Potentially Ictal Rhythmic Discharges [B(I)RDs] in Noncritically Ill Adults.

Brief potentially ictal rhythmic discharges (B(I)RDs) have been described in neonates and critically ill adults, and their association with seizures has been demonstrated. Their significance in noncritically ill adults remains unclear. We aimed to investigate their prevalence, electrographic characteristics, and clinical significance. We identified adult patients with B(I)RDs who received long-term EEG recordings either in the epilepsy monitoring unit or in the ambulatory setting. Patients with acute findings on imaging or status epilepticus were excluded. B(I)RDs were defined as very brief (<10 seconds) runs of focal or generalized sharply contoured rhythmic activity greater than 4 Hz, with or without evolution, that were not consistent with any known normal or benign pattern. The clinical history, EEG, and imaging results were retrieved. Each patient with B(I)RDs was matched by age and etiology to a control group with epileptiform discharges but without B(I)RDs in a 1:2 ratio. We identified B(I)RDs in 15 patients of 1,230 EEGs (1.2%). The pattern typically consisted of 0.5 to 4 second runs of sharply contoured alpha activity without evolution. All patients with B(I)RDs had epilepsy, and, when compared with controls with epilepsy but without BIRDs, were more likely to be medically refractory (10 of 15 [67%] vs. 5 of 30 [17%]; P < 0.01). All seizure onsets colocalized to the B(I)RDs, and most were morphologically similar. In noncritically ill patients, B(I)RDs are associated with refractory epilepsy and their location is correlated with the seizure onset area.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6months or longer and 14% experienced at least one seizure-free period of 1year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p=0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.