Using pre-surgical suspicion to guide insula implantation strategy.

Rationale: Insular epilepsy can be a challenging diagnosis due to overlapping semiology and scalp EEG findings with frontal, temporal, and parietal lobe epilepsies. Stereotactic electroencephalography (sEEG) provides an opportunity to better localize seizure onset. The possibility of improved localization is balanced by implantation risk in this vascularly rich anatomic region. We review both safety and pre-implantation factors involved in insular electrode placement across four years at an academic medical center. Methods: Presurgical data, operative reports, and invasive EEG summaries were retrospectively reviewed for patients undergoing invasive epilepsy monitoring on the insula from 2016 through 2019. EEG reports were reviewed to record the presence of insula ictal and interictal involvement. We recorded which presurgical findings suggested insular involvement (insula lesion on MRI, insula changes on PET/SPECT/scalp EEG, characteristic semiology, or history of failed anterior temporal lobectomy). The likelihood of pre-sEEG insular onset was categorized as low suspicion if no presurgical findings were present ("rule out"), moderate suspicion if one finding was present, and high suspicion if two or more findings were present. Results: 76 patients received 189 insular electrodes as part of their implantation strategy for 79 surgical cases. Seven patients (8.9%) had insular ictal onset. One clinically significant complication (left hemiparesis) occurred in a patient with moderate suspicion for insular onset. There were 38 low suspicion cases, 36 moderate suspicion cases, and 5 high suspicion cases for pre-sEEG insula ictal onset. Two low suspicion (5.3%), three moderate suspicion (8.6%), and two high suspicion (40%) cases had insular ictal onset. Conclusions: The insula can safely receive sEEG. Having two or more presurgical factors indicating insular onset is a strong, albeit incomplete, predictor of insular seizure onset. Using pre-implantation clinical findings can offer clinicians predictive value for targeting the insula during invasive EEG monitoring.

Infraclavicular de novo placement of a responsive neurostimulator for a patient with eloquent glioma-associated epilepsy: illustrative case.

BACKGROUND: The authors present a 50-year-old female with high-grade glioma involving the motor cortex as the cause of her drug-resistant epilepsy (DRE). Responsive neurostimulation (RNS) was chosen for epilepsy treatment. Due to concerns regarding the generator impeding the regular imaging surveillance required for treatment and monitoring of her glioma, surgeons placed the internal pulse generator (IPG) within an infraclavicular chest pocket. OBSERVATIONS: Implantation of the RNS device and IPG within the infraclavicular pocket was uneventful. However, both subdural and depth electrodes were used and connected to the IPG, and subdural electrodes are considerably shorter than depth electrodes (37 vs 44 cm). The shorter strip leads presumably generated significant tension, leading to fracture of the leads. Therefore, surgery was repeated using only depth electrodes for more length and less tension. The device has good-quality electrocorticography signals that continue to be used for device programming. The seizure burden was reduced, and quality of life improved for the patient. LESSONS: The RNS system with infraclavicular IPG placement reduced the seizure burden and improved the quality of life of a patient with glioma-associated epilepsy. Surgeons may consider the infraclavicular location as an alternative site for implantation for RNS candidates who require recurrent intracranial magnetic resonance imaging.

Source-sink connectivity: a novel interictal EEG marker for seizure localization.

Over 15 million epilepsy patients worldwide have drug-resistant epilepsy. Successful surgery is a standard of care treatment but can only be achieved through complete resection or disconnection of the epileptogenic zone, the brain region(s) where seizures originate. Surgical success rates vary between 20% and 80%, because no clinically validated biological markers of the epileptogenic zone exist. Localizing the epileptogenic zone is a costly and time-consuming process, which often requires days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity on individual channels occurring immediately before seizures or spikes that occur interictally (i.e. between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in epileptogenic zone localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. IEEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aimed to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the epileptogenic zone. We hypothesized that when a patient is not clinically seizing, it is because the epileptogenic zone is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighbouring nodes ('sources') and the inhibited nodes themselves ('sinks'). Specifically, patient-specific dynamical network models were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics. We validated the algorithm in a retrospective analysis of 65 patients. The source-sink metrics identified epileptogenic regions with 73% accuracy and clinicians agreed with the algorithm in 93% of seizure-free patients. The algorithm was further validated by using the metrics of the annotated epileptogenic zone to predict surgical outcomes. The source-sink metrics predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians' predictions (surgical success rate of this dataset). In failed outcomes, we identified brain regions with high metrics that were untreated. When compared with high frequency oscillations, the most commonly proposed interictal iEEG feature for epileptogenic zone localization, source-sink metrics outperformed in predictive power (by a factor of 1.2), suggesting they may be an interictal iEEG fingerprint of the epileptogenic zone.

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 25.5 months (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.

sEEG for expansion of a surgical epilepsy program: Safety and efficacy in 152 consecutive cases.

OBJECTIVE: Stereoelectroencephalography (sEEG) is an intracranial encephalography method of expanding use. The need for increased epilepsy surgery access has led to the consideration of sEEG adoption by new or expanding surgical epilepsy programs. Data regarding safety and efficacy are uncommon outside of high-volume, well-established centers, which may be less applicable to newer or low-volume centers. The objective of this study was to add to the sEEG outcomes in the literature from the perspective of a rapidly expanding center. METHODS: A retrospective chart review of consecutive sEEG cases from January 2016 to December 2019 was performed. Data extraction included demographic data, surgical data, and outcome data, which pertinently examined surgical method, progression to therapeutic procedure, clinically significant adverse events, and Engel outcomes. RESULTS: One hundred and fifty-two sEEG procedures were performed on 131 patients. Procedures averaged 10.5 electrodes for a total of 1603 electrodes. The majority (84%) of patients progressed to a therapeutic procedure. Six clinically significant complications occurred: three retained electrodes, two hemorrhages, and one failure to complete investigation. Only one complication resulted in a permanent deficit. Engel 1 outcome was achieved in 63.3% of patients reaching one-year follow-up after a curative procedure. SIGNIFICANCE: New or expanding epilepsy surgery centers can appropriately consider the use of sEEG. The complication rate is low and the majority of patients progress to therapeutic surgery. Procedural safety, progression to therapeutic intervention, and Engel outcomes are comparable to cohorts from long-established epilepsy surgery programs.

Cardiology perspective on seizure-related bradyarrhythmias and SUDEP: A survey study.

OBJECTIVE: To determine cardiologist knowledge of and experience with seizure-related bradyarrhythmias and sudden unexpected death in epilepsy (SUDEP). BACKGROUND: Autonomic changes related to acute seizures are common and can occur during the ictal or postictal period. Two concerning changes in these periods are significant bradycardia and asystole. Postictal asystole has been investigated as a potential mechanism for SUDEP. METHODS: A 27-question survey delivered to cardiologists and cardiology fellows assessed demographics, personal experience, and training involving SUDEP and seizure-related bradycardia and asystole. Following IRB approval, a list of US cardiology fellowships was constructed using the AAMC public website. Surveys were distributed by email to all programs whose program director or coordinator's email was readily available on their website. They were asked to forward the survey to both cardiology fellows and practicing cardiologists. RESULTS: Fifty one surveys were completed: 23 from fellows and 28 from practicing cardiologists. Forty nine were from academic centers. Twenty four respondents (47%) reported being consulted for ictal bradycardia or asystole. Nine and 13 recommended treatment for ictal bradycardia or ictal asystole, respectively. Nineteen respondents (37%) reported being consulted for postictal bradycardia or asystole. Eight recommended treatment for postictal bradycardia or asystole, respectively. Treatment recommendations included medical management and/or pacemaker. None reported a substantial knowledge of SUDEP. The most common response interrogating SUDEP awareness (63%) was "no knowledge of SUDEP". Formal SUDEP education was not reported by any participant with only one reporting formal didactics regarding seizure-related arrhythmias. DISCUSSION: Our results suggest ictal bradyarrhythmias are less commonly known to cardiologists, with SUDEP awareness being far less. Formal education to cardiologists on these two topics could prove beneficial at the intersection of cardiology and care for patients with epilepsy.

A prospective multicenter study of laser ablation for drug resistant epilepsy - One year outcomes.

OBJECTIVE: To report one-year seizure outcomes, procedural data, and quality of life scores following laser interstitial thermal therapy (LITT) of epileptogenic foci. METHODS: Data from an ongoing prospective, multi-center registry were assessed. Procedural information, Engel seizure outcomes, and quality of life (QoL) scores were analyzed. A responder analysis was performed to better understand potential clinical characteristics that could influence seizure outcome. RESULTS: Sixty patients have been enrolled into LAANTERN (Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System) specifically for epilepsy treatment, of which 42 reached one year follow up. Engel I outcome was achieved in 64.3 % at one year follow up. Patients with mesial temporal lobe epilepsy (MTLE) comprised 56.7 % of this cohort of multiple epilepsy types. Other significant etiologies included focal cortical dysplasia, hypothalamic hamartoma, cavernoma, heterotopias, and tuberous sclerosis. Median length of stay was 32.7 h. At discharge, head pain score averaged 1.4 ± 2.1 on a scale from 1 to 10. Five adverse events were reported, one categorized as serious. Seizure worry and social functioning scores improved significantly in quality of life measures. SIGNIFICANCE: Surgical treatment with LITT for epileptic foci is a safe and effective treatment option for people with drug resistant epilepsy. Our multicenter prospective seizure outcomes continue to expand published LITT experience in MTLE as well as non-MTLE epilepsies. The minimally invasive nature allows for short hospitalizations with minimal reported pain and discomfort.

A Randomized, Double-Blinded, Placebo-Controlled, Cross Over Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine.

INTRODUCTION: Daily oral beta-adrenoreceptor antagonist has been shown to be effective in preventing migraine headaches. Timolol 0.5% ophthalmic solution is a non-selective beta-adrenoreceptor antagonist, where the primary use is for glaucoma. There have been case reports that timolol is effective in aborting or improving an acute migraine headache. The objective of this study was to assess the efficacy (decrease of ≥ 50% in pain scale at 120 minutes) of timolol 0.5% ophthalmic solution compared to placebo in acute treatment of migraine headache. METHODS: We performed a randomized, double-blind, crossover, placebo-controlled, study. Study entry criteria required subjects to have one to eight migraine episodes per month. The primary outcome was comparison of the change in a visual analog pain scale (VAS) at 120 minutes after taking the study medication. Study subjects were given a pain scale with a range of 1 (no pain) to 10 (most severe pain) to complete after onset of migraine but before administration of study drops and 120 minutes after administration of study drops. Improvement was defined as a ≥ 50% decrease in pain scale. RESULTS: Nineteen subjects completed the study and were used for analysis. The primary outcome changes in pain scale, 120 minutes after dose, showed a similar decrease for placebo and drug with a slightly wider 95% CI for placebo. Six subjects in each arm experienced a ≥ 50% decrease in pain scale. CONCLUSION: These results support that timolol 0.5% ophthalmic solution is not an efficacious treatment for acute migraine headache.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".

Laser Ablation of Abnormal Neurological Tissue Using Robotic Neuroblate System (LAANTERN): Procedural Safety and Hospitalization.

BACKGROUND: Stereotactic laser ablation (SLA) has demonstrated potential utility for a spectrum of difficult to treat neurosurgical pathologies in multiple small and/or retrospective single-institutional series. Here, we present the safety profile of SLA of intracranial lesions from the Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN; Monteris Medical) multi-institutional, international prospective observational registry. OBJECTIVE: To determine the procedural safety of SLA for intracranial lesions. METHODS: Prospective procedural safety and hospitalization data from the first 100 treated LAANTERN patients was collected and analyzed. RESULTS: Mean age and baseline Karnofsky Performance Status (KPS) were 51(± 17) yr and 83(± 15), respectively. In total, 81.2% of patients had undergone prior surgical or radiation treatment. Most patients had a single lesion (79%) ablated through 1 burr hole (1.2 ± 0.7 per patient), immediately following a lesion biopsy. In total, >90% of the lesion was ablated in 72% of treated lesions. Average total procedural time was 188.2 ± 69.6 min, and average blood loss was 17.7 ± 55.6 ccs. The average length of intensive care unit (ICU) and hospital stays before discharge were 38.1 ± 62.7 h and 61.1 ± 87.2 h, respectively. There were 5 adverse events (AEs) attributable to SLA (5/100; 5%). After the procedure, 84.8% of patients were discharged home. There was 1 mortality within 30 d of the procedure (1/100; 1%), which was not attributable to SLA. CONCLUSION: SLA is a safe, minimally invasive procedure with favorable postprocedural ICU and hospital utilization profiles.

Patterns of Clinical Use of Stereotactic Laser Ablation: Analysis of a Multicenter Prospective Registry.

BACKGROUND: Stereotactic laser ablation (SLA), also termed laser interstitial thermal therapy, is a minimally invasive procedure that is increasingly used in neurosurgery. We wished to examine how and whether SLA is changing the landscape of treatment options for neurosurgical patients. METHODS: Patients undergoing stereotactic laser ablation were prospectively enrolled in the Laser Ablation of Abnormal Neurological Tissue (LAANTERN) registry. Data from the first 100 enrolled patients are presented here. RESULTS: Clinical indications for SLA include treatment of primary intracranial tumors (48%; 81% being high-grade gliomas [HGGs]), brain metastases (BMs, 34%), epilepsy (16%), and other (2%). For HGGs, SLA was equally likely used for newly diagnosed (45%) or previously treated/recurrent lesions (55%, P = 0.54). By contrast, SLA was predominantly used as treatment for BMs in which radiation therapy/radiosurgery had failed (91%), with only 9% of SLAs performed as initial treatment for newly diagnosed lesions (P < 0.001). Of all SLAs performed, 45% of the procedures were in lieu of surgical resection, with 43% performed because the lesion was not accessible by conventional neurosurgical techniques. CONCLUSION: HGGs and BMs are the leading indications for SLA in the LAANTERN study. For HGGs, SLA is equally used in the presenting or previously treated/recurrent setting. For BMs, SLA is typically used in the recurrent setting. SLAs are equally likely to be performed for difficult-to-access lesions or in lieu of conventional open surgery.

Unexpected Aphasia following Right Temporal Lobectomy as Treatment of Recurrent Super-Refractory Status Epilepticus.

BACKGROUND: Super-refractory status epilepticus (SRSE) is a critical neurological condition with a high mortality rate. There are only limited data to direct the treatment in SRSE, and surgery has been reported to successfully stop SRSE. We present a case of recurrent SRSE treated with urgent right temporal lobectomy in a right-handed woman which potentially saved her life but resulted in crossed sensory aphasia. CASE DESCRIPTION: A 61-year-old woman with a recent episode of prolonged focal SRSE due to right frontotemporal meningioma and hyperkalemia was admitted for recurrence of seizures that evolved to SRSE despite aggressive treatment with multiple fosphenytoin antiepileptic drugs (AEDs) and anesthetics. The patient underwent a right temporal lobectomy to remove the encephalomalacic and gliotic tissue around the meningioma that had been resected during a previous admission. Postoperatively the patient had a protracted course with modest improvement after stepwise reduction in her AEDs; however, her recovery unveiled a severe crossed aphasia. CONCLUSION: Resective surgery is an effective treatment option in the treatment of SRSE, although the recovery period can be protracted. Crossed aphasia after right temporal lobectomy should be considered in patients where it is not possible to complete a presurgical evaluation of higher cortical functions.

Postictal ammonia as a biomarker for electrographic convulsive seizures: A prospective study.

OBJECTIVE: Transient hyperammonemia (THA) was reported to follow generalized convulsions without sufficient evidence to confirm the epileptic nature of those events. We aimed to determine if postictal THA can differentiate between different types of events as confirmed electroencephalographically using video-electroencephalography (vEEG) monitoring. METHODS: In our prospective cohort, we screened all consented adults (>18 years) admitted to the epilepsy monitoring unit. Ammonia was checked at baseline, within 60 min of the event (for all patients) and 24 h after event (whenever possible). Patients were grouped into generalized convulsive seizures (GCS), psychogenic nonepileptic seizures with convulsions (PNES-C), or focal seizures (FS) based on vEEG. Data were analyzed using descriptive statistics and parametric/nonparametric methods. RESULTS: Of 78 patients enrolled, 13 had GCS, 8 had FS, and 9 had PNES-C. The groups were different with regard to gender (p = 0.04) and baseline ammonia (p = 0.02), but not age. The change in ammonia postictally from baseline was significantly different among the three groups (p = 0.004). The area under the receiver operator characteristic (ROC) curve for postictal ammonia to distinguish GCS from other groups was 0.88 (95% confidence interval [CI] 0.69-0.96) suggesting ammonia to be a good test differentiating epileptic GCS from other events. An ammonia level of ≥80 µmol/L correctly classified 80% of our patients (sensitivity 53.9%, specificity 100%). SIGNIFICANCE: Our results provide objective evidence for the association between THA and GCS seizures utilizing vEEG monitoring, and a basis for future studies to determine the role of postictal ammonia as an inexpensive diagnostic test to diagnose GCS.

Temporal lobe epilepsy in patients with nonlesional MRI and normal memory: an SEEG study.

OBJECT: Temporal lobe epilepsy (TLE) in the absence of MRI abnormalities and memory deficits is often presumed to have an extramesial or even extratemporal source. In this paper the authors report the results of a comprehensive stereoelectroencephalography (SEEG) analysis in patients with TLE with normal MRI images and memory scores. METHODS: Eighteen patients with medically refractory epilepsy who also had unremarkable MR images and normal verbal and visual memory scores on neuropsychological testing were included in the study. All patients had seizure semiology and video electroencephalography (EEG) findings suggestive of TLE. A standardized SEEG investigation was performed for each patient with electrodes implanted into the mesial and lateral temporal lobe, temporal tip, posterior temporal neocortex, orbitomesiobasal frontal lobe, posterior cingulate gyrus, and insula. This information was used to plan subsequent surgical management. RESULTS: Interictal SEEG abnormalities were observed in the mesial temporal structures in 17 patients (94%) and in the temporal tip in 6 (33%). Seizure onset was exclusively from mesial structures in 13 (72%), exclusively from lateral temporal cortex and/or temporal tip structures in 2 (11%), and independently from mesial and neocortical foci in 3 (17%). No seizure activity was observed arising from any extratemporal location. All patients underwent surgical intervention targeting the temporal lobe and tailored to the SEEG findings, and all experienced significant improvement in seizure frequency with a postoperative follow-up observation period of at least 1 year. CONCLUSIONS: This study demonstrates 3 important findings: 1) normal memory does not preclude mesial temporal seizure onset; 2) onset of seizures exclusively from mesial temporal structures without early neocortical involvement is common, even in the absence of memory deficits; and 3) extratemporal seizure onset is rare when video EEG and semiology are consistent with focal TLE.

Mesial temporal lobe epilepsy: a distinct electroclinical subtype of temporal lobe epilepsy.

Mesial temporal lobe epilepsy is a common subtype of temporal lobe epilepsy. Its most common cause is hippocampal sclerosis, which contributes to its distinct electroclinical phenotype that is seen commonly in the epilepsy monitoring unit setting. The common electrophysiological data show anterior temporal interictal sharp waves as well as rhythmic theta activity in the same localization. While the electrophysiological data can at times be misleading, its stereotyped and characteristic semiology can often allow for accurate diagnosis on its own. As patients with mesial temporal lobe epilepsy often fail medical therapy, surgical therapy can be considered. Early accurate diagnosis in these patients is essential for optimal care.

The feasibility and impact of midnight routine blood draws on laboratory orders and processing time.

OBJECTIVES: To evaluate the feasibility of midnight routine blood draws and assess their impact on test result availability and stat laboratory orders. METHODS: We changed the timing of routine blood draws from early morning to midnight on five inpatient wards during the period November 16 to 30, 2011. RESULTS: For the entire institution, of all orders placed each day, laboratory test orders placed from 4:00 to 8:00 am decreased from 55% to 39%, and those placed from 12:00 to 4:00 am increased from 12% to 30%. Stat orders per day decreased during the intervention period (301 ± 53 vs 344 ± 55, P = .04). Morning specimens were more likely to be available by 9:00am (78.1% vs 58.9%, P < .001), and their turnaround time improved by 25.8 minutes (158 vs 184 minutes, P < .001). Patient survey revealed potential preference for midnight blood draws. CONCLUSIONS: Midnight is a feasible alternative for the timing of routine blood draws. Redesigning inflow of laboratory orders improved efficiency of laboratory processing and reduced stat orders.

A case report of a Wada test after dominant hemisphere multiple hippocampal transections: Pathophysiology of confusion after amobarbital injection.

Dialepsis is defined as a predominant alteration of consciousness with preservation of motor tone and the ability to perform movements. While dialepsis is a common feature of both focal and generalized epilepsies, its precise symptomatogenic zone and pathogenesis remain undefined. This case report describes a patient who underwent intracarotid amobarbital procedures before and after dominant hemisphere multiple hippocampal transections. From our observations, we propose a possible pathogenesis for the generation of dialeptic seizures.