Combined neuromodulation and resection for functional cortex epilepsy: a case series.

OBJECTIVE: Medically refractory epilepsy (MRE) often requires resection of the seizure onset zone (SOZ) for effective treatment. However, when the SOZ is in functional cortex (FC), achieving complete and safe resection becomes difficult, due to the seizure network overlap with function. The authors aimed to assess the safety and outcomes of a combined approach involving partial resection combined with focal neuromodulation for FC refractory epilepsy. METHODS: The authors performed a retrospective analysis of individuals diagnosed with MRE who underwent surgical intervention from January 2015 to December 2022. Patients whose SOZ was located in FC and were treated with resection combined with simultaneous implantation of a focal neuromodulation device (responsive neurostimulation [RNS] device) with more than 12 months of follow-up data were included. All patients underwent a standard epilepsy preoperative assessment including intracranial electroencephalography and extraoperative stimulation mapping. Resections were performed under general anesthesia, followed by the concurrent implantation of an RNS device. RESULTS: Seven patients (4 males, median age 32.3 years, all right-handed) were included. The median interval from seizure onset to surgery was 17.4 years. The epileptogenic network included sensorimotor areas (cases 2, 3, and 6), visual cortex (case 1), language areas (cases 4 and 7), and the insula (case 5). The median follow-up was 3 years (range 1-5.8 years). No significant changes in neuropsychological tests were reported. One permanent nondisabling planned neurological deficit (left inferior quadrantanopia) was observed. Six patients had stimulation activated at a median of 4.7 months after resection. All patients achieved good seizure outcomes (5 with Engel class I and 2 with Engel class II outcomes). CONCLUSIONS: Maximal safe resection combined with focal neuromodulation presents a promising alternative to stand-alone resections for MRE epileptogenic zones overlapping with functional brain. This combined approach prioritizes the preservation of function while improving seizure outcomes.

A multicenter retrospective study of patients treated in the thalamus with responsive neurostimulation.

Introduction: For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. Methods: This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. Results: Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. Discussion: Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.

Factors Predicting Outcome After Intracranial EEG Evaluation in Patients With Medically Refractory Epilepsy.

BACKGROUND AND OBJECTIVES: The aim of this study was to identify predictors of a resective surgery and subsequent seizure freedom following intracranial EEG (ICEEG) for seizure-onset localization. METHODS: This is a retrospective chart review of 178 consecutive patients with medically refractory epilepsy who underwent ICEEG monitoring from 2002 to 2015. Univariable and multivariable regression analysis identified independent predictors of resection vs other options. Stepwise Akaike information criteria with the aid of clinical consideration were used to select the best multivariable model for predicting resection and outcome. Discrete time survival analysis was used to analyze the factors predicting seizure-free outcome. Cumulative probability of seizure freedom was analyzed using Kaplan-Meier curves and compared between resection and nonresection groups. Additional univariate analysis was performed on 8 select clinical scenarios commonly encountered during epilepsy surgical evaluations. RESULTS: Multivariable analysis identified the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant as independent predictors of resection (p < 0.0001, area under the receiver operating characteristic curve 0.80, 95% CI 0.73-0.87). Focal ICEEG onset and undergoing a resective surgery predicted absolute seizure freedom at the 5-year follow-up. Patients who underwent resective surgery were more likely to be seizure-free at 5 years compared with continued medical treatment or neuromodulation (60% vs 7%; p < 0.0001, hazard ratio 0.16, 95% CI 0.09-0.28). Even patients thought to have unfavorable predictors (nonlesional MRI or extratemporal lobe hypothesis or dominant hemisphere implant) had ≥50% chance of seizure freedom at 5 years if they underwent resection. DISCUSSION: Unfavorable predictors, including having nonlesional extratemporal epilepsy, should not deter a thorough presurgical evaluation, including with invasive recordings in many cases. Resective surgery without functional impairment offers the best chance for sustained seizure freedom and should always be considered first. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant are independent predictors of resection. Focal ICEEG onset and undergoing resection are independent predictors of 5-year seizure freedom.

Impact of Frailty on Morbidity and Mortality in Adult Patients Undergoing Surgical Evacuation of Acute Traumatic Subdural Hematoma.

OBJECTIVE: To determine whether baseline frailty is an independent predictor of extended hospital length of stay (LOS), nonroutine discharge, and in-hospital mortality after evacuation of an acute traumatic subdural hematoma (SDH). METHODS: A retrospective cohort study was performed. All adult patients who underwent surgery for an acute traumatic SDH were identified using the National Trauma Database from the year 2017. Patients were categorized into 3 cohorts based on the criteria of the 5-item modified frailty index (mFI-5): mFI = 0, mFI = 1, or mFI = 2+. A multivariate logistic regression analysis was used to identify independent predictors of extended LOS, nonroutine discharge, and in-hospital mortality. RESULTS: Of the 2620 patients identified, 41.7% were classified as mFI = 0, 32.7% as mFI = 1, and 25.6% as mFI = 2+. Rates of extended LOS and in-hospital mortality did differ significantly between the cohorts, with the mFI = 0 cohort most often experiencing a prolonged LOS (mFI = 0: 29.41% vs. mFI = 1: 19.45% vs. mFI = 2+: 19.73%, P < 0.001) and in-hospital mortality (mFI = 0: 24.66% vs. mFI = 1: 18.11% vs. mFI = 2+: 21.58%, P = 0.002). On multivariate regression analysis, when compared with mFI = 0, mFI = 2+ (odds ratio 1.4, P = 0.03) predicted extended LOS and nonroutine discharge (odds ratio 1.61, P = 0.001). CONCLUSIONS: Our study demonstrates that baseline frailty may be an independent predictor of extended LOS and nonroutine discharge, but not in-hospital mortality, in patients undergoing evacuation for an acute traumatic SDH. Further investigations are warranted as they may guide treatment plans and reduce health care expenditures for frail patients with SDH.

ASSFN Position Statement on Deep Brain Stimulation for Medication-Refractory Epilepsy.

Neuromodulation has taken a foothold in the landscape of surgical treatment for medically refractory epilepsies and offers additional surgical treatment options for patients who are not candidates for resective/ablative surgery. Approximately one third of patients with epilepsy suffer with medication-refractory epilepsy. A persistent underuse of epilepsy surgery exists. Neuromodulation treatments including deep brain stimulation (DBS) expand the surgical options for patients with epilepsy and provide options for patients who are not candidates for resective surgery. DBS of the bilateral anterior nucleus of the thalamus is an Food and Drug Administration-approved, safe, and efficacious treatment option for patients with refractory focal epilepsy. The purpose of this consensus position statement is to summarize evidence, provide recommendations, and identify indications and populations for future investigation in DBS for epilepsy. The recommendations of the American Society of Functional and Stereotactic Neurosurgeons are based on several randomized and blinded clinical trials with high-quality data to support the use of DBS to the anterior nucleus of the thalamus for the treatment of refractory focal-onset seizures.

Cortical low-frequency power correlates with behavioral impairment in animal model of focal limbic seizures.

OBJECTIVE: Impairment in consciousness is a debilitating symptom during and after seizures; however, its mechanism remains unclear. Limbic seizures have been shown to spread to arousal circuitry to result in a "network inhibition" phenomenon. However, prior animal model studies did not relate physiological network changes to behavioral responses during or following seizures. METHODS: Focal onset limbic seizures were induced while rats were performing an operant conditioned behavioral task requiring response to an auditory stimulus to quantify how and when impairment of behavioral response occurs. Correct responses were rewarded with sucrose. Cortical and hippocampal electrophysiology measured by local field potential recordings was analyzed for changes in low- and high-frequency power in relation to behavioral responsiveness during seizures. RESULTS: As seen in patients with seizures, ictal (p < .0001) and postictal (p = .0015) responsiveness was variably impaired. Analysis of cortical and hippocampal electrophysiology revealed that ictal (p = .002) and postictal (p = .009) frontal cortical low-frequency 3-6-Hz power was associated with poor behavioral performance. In contrast, the hippocampus showed increased power over a wide frequency range during seizures, and suppression postictally, neither of which were related to behavioral impairment. SIGNIFICANCE: These findings support prior human studies of temporal lobe epilepsy as well as anesthetized animal models suggesting that focal limbic seizures depress consciousness through remote network effects on the cortex, rather than through local hippocampal involvement. By identifying the cortical physiological changes associated with impaired arousal and responsiveness in focal seizures, these results may help guide future therapies to restore ictal and postictal consciousness, improving quality of life for people with epilepsy.

Sex-based differences in helmet performance in bicycle trauma.

OBJECTIVES: To determine the existence of sex-based differences in the protective effects of helmets against common injuries in bicycle trauma. METHODS: In a retrospective cohort study, we identified patients 18 years or older in the 2017 National Trauma Database presenting after bicycle crash. Sex-disaggregated and sex-combined multivariable logistic regression models were calculated for short-term outcomes that included age, involvement with motor vehicle collision, anticoagulant use, bleeding disorder and helmet use. The sex-combined model included an interaction term for sex and helmet use. The resulting exponentiated model parameter yields an adjusted OR ratio of the effects of helmet use for females compared with males. RESULTS: In total, 18 604 patients of average age 48.1 were identified, and 18% were female. Helmet use was greater in females than males (48.0% vs 34.2%, p<0.001). Compared with helmeted males, helmeted females had greater rates of serious head injury (37.7% vs 29.9%, p<0.001) despite less injury overall. In sex-disaggregated models, helmet use reduced odds of intracranial haemorrhage and death in males (p<0.001) but not females. In sex-combined models, helmets conferred to females significantly less odds reduction for severe head injury (p=0.002), intracranial bleeding (p<0.001), skull fractures (p=0.001), cranial surgery (p=0.006) and death (p=0.017). There was no difference for cervical spine fracture. CONCLUSIONS: Bicycle helmets may offer less protection to females compared with males. The cause of this sex or gender-based difference is uncertain, but there may be intrinsic incompatibility between available helmets and female anatomy and/or sex disparity in helmet testing standards.

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl- channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.

Thalamic Stimulation Improves Postictal Cortical Arousal and Behavior.

The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy.SIGNIFICANCE STATEMENT The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.

Deep Brain Stimulation Target Selection in Co-Morbid Essential Tremor and Parkinson's Disease.

Clinical Vignette: A 64-year-old man with essential tremor (ET) and Parkinson's disease (PD) presented with medically refractory, large amplitude, debilitating rest and action tremor in his extremities. Clinical Dilemma: Ventral intermediate nucleus of the thalamus (VIM) deep brain stimulation (DBS) improves tremor in ET and PD but does not ameliorate bradykinesia and rigidity in PD. The comparative efficacy of subthalamic nucleus (STN) DBS in managing action ET tremor remains unclear. Clinical Solution: Bilateral STN was selected as the DBS target. Moderate improvement in rest tremor and mild improvement in action tremor were noted following initial programming. Gap In Knowledge: There are no head-to-head trials to guide DBS target selection in patients with both ET and PD. Current evidence is limited to a few small head-to-head trials that have demonstrated equivalent efficacy in tremor reduction in PD patients using VIM as DBS target and in ET patients using STN. Expert Commentary: Due to limited evidence, DBS treatment of complex cases, such as combined Parkinson's disease and essential tremor, remains based on expert consensus at each institution. Further multi-approach efforts, using imaging, electrophysiologic, and animal data, will be needed to answer the identified gap in knowledge. Highlights: There is limited evidence to guide deep brain target selection in patients with essential tremor and Parkinson's disease. We review existing literature and propose strategies to manage tremor in these patients.

Beyond implantation effect? Long-term seizure reduction and freedom following intracranial monitoring without additional surgical interventions.

The term 'implantation effect' is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients.

How technology is driving the landscape of epilepsy surgery.

This article emphasizes the role of the technological progress in changing the landscape of epilepsy surgery and provides a critical appraisal of robotic applications, laser interstitial thermal therapy, intraoperative imaging, wireless recording, new neuromodulation techniques, and high-intensity focused ultrasound. Specifically, (a) it relativizes the current hype in using robots for stereo-electroencephalography (SEEG) to increase the accuracy of depth electrode placement and save operating time; (b) discusses the drawback of laser interstitial thermal therapy (LITT) when it comes to the need for adequate histopathologic specimen and the fact that the concept of stereotactic disconnection is not new; (c) addresses the ratio between the benefits and expenditure of using intraoperative magnetic resonance imaging (MRI), that is, the high technical and personnel expertise needed that might restrict its use to centers with a high case load, including those unrelated to epilepsy; (d) soberly reviews the advantages, disadvantages, and future potentials of neuromodulation techniques with special emphasis on the differences between closed and open-loop systems; and (e) provides a critical outlook on the clinical implications of focused ultrasound, wireless recording, and multipurpose electrodes that are already on the horizon. This outlook shows that although current ultrasonic systems do have some limitations in delivering the acoustic energy, further advance of this technique may lead to novel treatment paradigms. Furthermore, it highlights that new data streams from multipurpose electrodes and wireless transmission of intracranial recordings will become available soon once some critical developments will be achieved such as electrode fidelity, data processing and storage, heat conduction as well as rechargeable technology. A better understanding of modern epilepsy surgery will help to demystify epilepsy surgery for the patients and the treating physicians and thereby reduce the surgical treatment gap.

Preresidency Publication Productivity of U.S. Neurosurgery Interns.

BACKGROUND: Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The preresidency publication volume of U.S. neurosurgery interns and any potential association between applicant publication volume and the match results of top-ranked residency programs have not been well characterized. OBJECTIVE: In this study, we sought to characterize the preresidency publication volume of U.S. neurosurgery residents in the 2018-2019 intern class using the Scopus database. METHODS: For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Preresidency publication volumes of interns at the top-25 programs (based on a composite ranking score according to 4 different ranking metrics) were compared with those at all other programs. RESULTS: We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least 1 publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± standard error of the mean). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs. 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs. 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs. 5.7 ± 0.8, P = 0.0267) compared with interns at all other programs. CONCLUSIONS: Our results provide a general estimate of the preresidency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching in the top-25 neurosurgery residency programs.

Default mode and visual network activity in an attention task: Direct measurement with intracranial EEG.

Dynamic attention states are necessary to navigate the ever changing task demands of daily life. Previous investigations commonly utilize a block paradigm to study sustained and transient changes in attention networks. fMRI investigations have shown that sustained attention in visual block design attention tasks corresponds to decreased signal in the default mode and visual processing networks. While task negative networks are anticipated to decrease during active task engagement, it is unexpected that visual networks would also be suppressed during a visual task where event-related fMRI studies have found transient increases to visual stimuli. To resolve these competing results, the current investigations utilized intracranial EEG to directly interrogate visual and default mode network dynamics during a visual continuous performance task. We used the electrophysiological data to model expected fMRI signals and to maximize interpretation of current results with previous investigations. Results show broadband gamma power decreases in the default mode network, corresponding to previous EEG and fMRI findings. Meanwhile, visual processing regions including the primary visual cortex and fusiform gyrus demonstrate both sustained decreases during task engagement and stimuli-driven transient increases in gamma power. Modeled fMRI based on gamma power reproduces signal decreases reported in the fMRI literature, and emphasizes the insensitivity of fMRI to transient, regularly spaced signal changes embedded within sustained network dynamics. The signal processing functions of the dynamic visual and default mode network changes explored in this study are unknown but may be elucidated through further investigation.

A Switch and Wave of Neuronal Activity in the Cerebral Cortex During the First Second of Conscious Perception.

Conscious perception occurs within less than 1 s. To study events on this time scale we used direct electrical recordings from the human cerebral cortex during a conscious visual perception task. Faces were presented at individually titrated visual threshold for 9 subjects while measuring broadband 40-115 Hz gamma power in a total of 1621 intracranial electrodes widely distributed in both hemispheres. Surface maps and k-means clustering analysis showed initial activation of visual cortex for both perceived and non-perceived stimuli. However, only stimuli reported as perceived then elicited a forward-sweeping wave of activity throughout the cerebral cortex accompanied by large-scale network switching. Specifically, a monophasic wave of broadband gamma activation moves through bilateral association cortex at a rate of approximately 150 mm/s and eventually reenters visual cortex for perceived but not for non-perceived stimuli. Meanwhile, the default mode network and the initial visual cortex and higher association cortex networks are switched off for the duration of conscious stimulus processing. Based on these findings, we propose a new "switch-and-wave" model for the processing of consciously perceived stimuli. These findings are important for understanding normal conscious perception and may also shed light on its vulnerability to disruption by brain disorders.

Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study.

BACKGROUND: Facial pain response (PR) to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is much less optimal. No large patient series regarding stereotactic radiosurgery (SRS) has been published. OBJECTIVE: To evaluate the clinical outcomes of MS-related TN treated with SRS. METHODS: This is a retrospective cohort study. A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study. RESULTS: The median latency period of PR after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute [BNI] Pain Scores I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%). CONCLUSION: In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control.

Seizure susceptibility and infraslow modulatory activity in the intracranial electroencephalogram.

OBJECTIVE: Studies of infraslow amplitude modulations (<0.15 Hz) 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. METHODS: 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 <0.15 Hz 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 6 hours removed from other seizures and analyzed infraslow envelope MSC before and after them. RESULTS: 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 3 hours preseizure and 1 hour 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 3 hours preseizure, then showing progressive desynchronization from 3 hours preseizure to 1 hour postseizure. SIGNIFICANCE: 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.

Expanding Brain-Computer Interfaces for Controlling Epilepsy Networks: Novel Thalamic Responsive Neurostimulation in Refractory Epilepsy.

Seizures have traditionally been considered hypersynchronous excitatory events and epilepsy has been separated into focal and generalized epilepsy based largely on the spatial distribution of brain regions involved at seizure onset. Epilepsy, however, is increasingly recognized as a complex network disorder that may be distributed and dynamic. Responsive neurostimulation (RNS) is a recent technology that utilizes intracranial electroencephalography (EEG) to detect seizures and delivers stimulation to cortical and subcortical brain structures for seizure control. RNS has particular significance in the clinical treatment of medically refractory epilepsy and brain-computer interfaces in epilepsy. Closed loop RNS represents an important step forward to understand and target nodes in the seizure network. The thalamus is a central network node within several functional networks and regulates input to the cortex; clinically, several thalamic nuclei are safe and feasible targets. We highlight the network theory of epilepsy, potential targets for neuromodulation in epilepsy and the first reported use of RNS as a first generation brain-computer interface to detect and stimulate the centromedian intralaminar thalamic nucleus in a patient with bilateral cortical onset of seizures. We propose that advances in network analysis and neuromodulatory techniques using brain-computer interfaces will significantly improve outcomes in patients with epilepsy. There are numerous avenues of future direction in brain-computer interface devices including multi-modal sensors, flexible electrode arrays, multi-site targeting, and wireless communication.

Management of Subdural Hematomas: Part II. Surgical Management of Subdural Hematomas.

PURPOSE OF REVIEW: Management of patients with subdural hematomas starts with Emergency Neurological Life Support guidelines. Patients with acute or chronic subdural hematomas (SDHs) associated with rapidly deteriorating neurologic exam, unilaterally or bilaterally dilated nonreactive pupils, and extensor posturing are considered imminently surgical; likewise, SDHs more than 10 mm in size or those associated with more than 5-mm midline shift are deemed operative. RECENT FINDINGS: While twist drill craniostomy and placement of subdural evacuating vport system (SEPS) are quick, bedside procedures completed under local anesthesia and appropriate for patients with chronic SDH or patients that cannot tolerate anesthesia, these techniques are not optimal for patients with acute SDH or chronic SDH with septations. Burr hole SDH evacuation under conscious sedation or general anesthesia is an analogous technique; however, it requires basic surgical equipment and operating room staff, with a focus on a closed system with burr hole followed by rapid drain placement to avoid introduction of air into the subdural space, or multiple burr holes with extensive irrigation to reduce pneumocephalus and continue SDH evacuation via drain for several days. Acute SDH associated with significant mass effect and cerebral edema requires aggressive decompression via craniotomy with clot evacuation and frequently a craniectomy. Chronic SDHs that fail conservative management and progress clinically or radiographically are addressed with craniotomy with or without membranectomy. Surgical SDH management is variable depending on its characteristics and etiology, patient's functional status, comorbidities, goals of care, institutional preferences, and availability of specialized surgical equipment and adjunct therapies. Rapid access to surgical suites and trained staff to address surgical hemorrhages in a timely manner, with appropriate post-operative care by a specialized team including neurosurgeons and neurointensivists, is of paramount importance for successful patient outcomes. Here, we review various aspects of surgical SDH management.

Management of Subdural Hematomas: Part I. Medical Management of Subdural Hematomas.

PURPOSE OF REVIEW: Subdural hematomas (SDH) represent common neurosurgical problem associated with significant morbidity, mortality, and high recurrence rates. SDH incidence increases with age; numbers of patients affected by SDH continue to rise with our aging population and increasing number of people taking antiplatelet agents or anticoagulation. Medical and surgical SDH management remains a subject of investigation. RECENT FINDINGS: Initial management of patients with concern for altered mental status with or without trauma starts with Emergency Neurological Life Support (ENLS) guidelines, with a focus on maintaining ICP < 22 mmHg, CPP > 60 mmHg, MAP 80-110 mmHg, and PaO2 > 60 mmHg, followed by rapid sequence intubation if necessary, and expedited acquisition of imaging to identify a space-occupying lesion. Patients are administered anti-seizure medications, and their antiplatelet medications or anticoagulation may be reversed if neurosurgical interventions are anticipated, or until hemorrhage is stabilized on imaging. Medical SDH care focuses on (a) management of intracranial hypertension; (b) maintenance of adequate cerebral perfusion; (c) seizure prevention and treatment; (d) maintenance of normothermia, eucarbia, euglycemia, and euvolemia; and (e) early initiation of enteral feeding, mobilization, and physical therapy. Post-operatively, SDH patients require ICU level care and are co-managed by neurointensivists with expertise in treating increased intracranial pressure, seizures, and status epilepticus, as well as medical complications of critical illness. Here, we review various aspects of medical management with a brief overview of pertinent literature and clinical trials for patients diagnosed with SDH.