Is preserved consciousness during seizures associated with quality of life among patients with drug-resistant epilepsy?

Drug-resistant epilepsy is associated with reduced quality of life (QoL) due to a myriad of disease-related and psychosocial factors. Although consciousness during seizures is a core feature of seizure classification, its impact on QoL in people with epilepsy (PWE) is not well understood. This study aimed to address this gap by comparing QoL between PWE with focal aware (FA) versus impaired awareness (FIA) seizures. Sixty-nine adults with epilepsy completed the Quality of Life in Epilepsy-31 (QoLIE-31) inventory as part of their pre-surgical neuropsychological evaluation (FA: n = 26, FIA: n = 43). There was no group difference in seizure burden as defined by the proportion of comorbid focal to bilateral tonic-clonic seizures (FA:65.4 %; FIA: 79.1 %). People with FA seizures reported lower overall QoL than people with FIA seizures; sub-scale analyses revealed that seizure worry drives this effect. There was no difference in QoL between people with motor and non-motor FA seizures. Results suggest that FA seizures are burdensome on the QoL of PWE. FA seizures may contribute to seizure worry due to preserved awareness of aversive peri-ictal phenomenon. Findings suggest that clinical efforts should continue to be made to optimize seizure control in people with breakthrough FA seizures. Prospective longitudinal monitoring of QoL in trials of consciousness-targeting neurostimulation therapy is needed to determine if QoL changes as a function of improved peri-ictal consciousness following treatment.

Musicogenic epilepsy: Expanding the spectrum of glutamic acid decarboxylase 65 neurological autoimmunity.

The objective of this study was to describe serological association of musicogenic epilepsy and to evaluate clinical features and outcomes of seropositive cases. Through retrospective chart review, musicogenic epilepsy patients were identified. Among 16 musicogenic epilepsy patients, nine underwent autoantibody evaluations and all had high-titer glutamic acid decarboxylase 65-immunoglobulin G (GAD65-IgG; >20 nmol·L-1 , serum, normal ≤ .02 nmol·L-1 , eight women). Median GAD65-IgG serum titer was 294 nmol·L-1 (20.3-3005 nmol·L-1 ), and median cerebrospinal fluid titer (n = 4) was 14.7 nmol·L-1 . All patients had temporal lobe epilepsy, and bitemporal epileptiform abnormalities were common. Right temporal lobe seizures were most frequently captured when seizures were induced by music on electroencephalogram (3/4; 75%). Intravenous (IV) methylprednisolone and/or IV Ig (IVIG) was utilized in four patients, with one having greater than 50% reduction. Rituximab (n = 2) and mycophenolate (n = 1) were ineffective. Two patients underwent right temporal lobe resections but continued to have seizures. Vagus nerve stimulation was effective at reducing seizures in one patient by 50%, and an additional patient was seizure-free by avoiding provoking music. Right temporal lobe epilepsy was more common among patients with musicogenic epilepsy when compared to nonmusicogenic GAD65 epilepsies (n = 71, 89% vs. 47%, p = .03). GAD65-IgG should be tested in patients with musicogenic epilepsy, given implications for management and screening for comorbid autoimmune conditions.

Injection of prophylactic lorazepam versus antiseizure drugs on the localization value of ictal SPECT studies and treatment-emergent adverse events: A single-center prospective study.

OBJECTIVE: We aimed to examine the impact of resumption of home antiseizure drugs alone (ASD-) compared with adjunct administration of scheduled intravenous (IV) lorazepam 2 mg every 6 h (ASD+) following ictal single-photon emission computed tomography (SPECT) injection on the localization value of SPECT studies and treatment-emergent adverse events (TEAEs). METHODS: We conducted a prospective study at Mayo Clinic inpatient epilepsy monitoring unit (EMU) between January 2018 and May 2020 in Jacksonville, Florida. The ASD- and ASD+ groups were compared for concordance of SPECT studies with the epilepsy surgical conference (ESC) consensus or intracranial electroencephalography (icEEG) findings as reference. Treatment-emergent adverse events, obtained from surveys at 24 h and one week postictal SPECT injection, were also compared between both groups. RESULTS: Twenty-two consecutive patients with temporal (eight patients, 36%) and extratemporal (14 patients, 64%) epilepsy were included: 12 ASD+ and 10 ASD-. The two groups were well matched with regard to clinical and ictal SPECT injection characteristics including the occurrence of seizure between ictal and interictal SPECT injections. The localization value of SPECT studies was similar in the two groups. Patients in the ASD+ group reported higher rates of dizziness and excessive sedation at 24 h (p-value = 0.008). Fourteen patients (64%) underwent icEEG monitoring. For the entire cohort, the localization concordance of SPECT analysis by statistical parametric mapping (SPM) was superior to raw ictal SPECT (p-value = 0.003) and subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM; p-value = 0.021). Eventually, seven patients (31.8%) underwent resective brain surgery of whom four (57.1%) became seizure-free (median follow-up = 22 months). CONCLUSIONS: Our findings suggest that resuming home ASDs without the addition of scheduled IV lorazepam following inpatient ictal SPECT injection is equally efficacious for seizure onset zone (SOZ) localization on SPECT studies, especially SPM. This approach is also associated with fewer transient TEAEs and lower financial cost with no difference in preventing seizure between ictal and interictal SPECT injections.

Potential differences between monolingual and bilingual patients in approach and outcome after awake brain surgery.

INTRODUCTION: 20.8% of the United States population and 67% of the European population speak two or more languages. Intraoperative different languages, mapping, and localization are crucial. This investigation aims to address three questions between BL and ML patients: (1) Are there differences in complications (i.e. seizures) and DECS techniques during intra-operative brain mapping? (2) Is EOR different? and (3) Are there differences in the recovery pattern post-surgery? METHODS: Data from 56 patients that underwent left-sided awake craniotomy for tumors infiltrating possible dominant hemisphere language areas from September 2016 to June 2019 were identified and analyzed in this study; 14 BL and 42 ML control patients. Patient demographics, education level, and the age of language acquisition were documented and evaluated. fMRI was performed on all participants. RESULTS: 0 (0%) BL and 3 (7%) ML experienced intraoperative seizures (P = 0.73). BL patients received a higher direct DECS current in comparison to the ML patients (average = 4.7, 3.8, respectively, P = 0.03). The extent of resection was higher in ML patients in comparison to the BL patients (80.9 vs. 64.8, respectively, P = 0.04). The post-operative KPS scores were higher in BL patients in comparison to ML patients (84.3, 77.4, respectively, P = 0.03). BL showed lower drop in post-operative KPS in comparison to ML patients (- 4.3, - 8.7, respectively, P = 0.03). CONCLUSION: We show that BL patients have a lower incidence of intra-operative seizures, lower EOR, higher post-operative KPS and tolerate higher DECS current, in comparison to ML patients.

Ezio Sciamanna: The Italian contribution to the origin of cortical stimulation mapping in humans.

Influenced by Ferrier's 1873 publication documenting his initial experience with cortical stimulation mapping (CSM) across several species, 19th-century experiments applying electric current to exposed human brain soon followed. Bartholow is commonly credited with the first report of CSM in a conscious human in 1874. What is not well established is that prominent Italian neurologist, Ezio Sciamanna, localized sensorimotor function in a human demonstration of CSM shortly thereafter in 1882. Sciamanna was in the vanguard of functional localization of brain function through direct stimulation of human gray matter. Unlike Bartholow, who has been canonized in the annals of CSM, Sciamanna has remained relatively obscure, despite the fact that his case may represent a better example of true subdural CSM than his better known contemporary.

Proceedings of the Eighth International Workshop on Advances in Electrocorticography.

Excerpted proceedings of the Eighth International Workshop on Advances in Electrocorticography (ECoG), which convened October 15-16, 2015 in Chicago, IL, are presented. The workshop series has become the foremost gathering to present current basic and clinical research in subdural brain signal recording and analysis.

Proceedings of the Seventh International Workshop on Advances in Electrocorticography.

The Seventh International Workshop on Advances in Electrocorticography (ECoG) convened in Washington, DC, on November 13-14, 2014. Electrocorticography-based research continues to proliferate widely across basic science and clinical disciplines. The 2014 workshop highlighted advances in neurolinguistics, brain-computer interface, functional mapping, and seizure termination facilitated by advances in the recording and analysis of the ECoG signal. The following proceedings document summarizes the content of this successful multidisciplinary gathering.

Proceedings of the Fifth International Workshop on Advances in Electrocorticography.

The Fifth International Workshop on Advances in Electrocorticography convened in San Diego, CA, on November 7-8, 2013. Advancements in methodology, implementation, and commercialization across both research and in the interval year since the last workshop were the focus of the gathering. Electrocorticography (ECoG) is now firmly established as a preferred signal source for advanced research in functional, cognitive, and neuroprosthetic domains. Published output in ECoG fields has increased tenfold in the past decade. These proceedings attempt to summarize the state of the art.

Neural populations in the language network differ in the size of their temporal receptive windows.

Despite long knowing what brain areas support language comprehension, our knowledge of the neural computations that these frontal and temporal regions implement remains limited. One important unresolved question concerns functional differences among the neural populations that comprise the language network. Here we leveraged the high spatiotemporal resolution of human intracranial recordings (n = 22) to examine responses to sentences and linguistically degraded conditions. We discovered three response profiles that differ in their temporal dynamics. These profiles appear to reflect different temporal receptive windows, with average windows of about 1, 4 and 6 words, respectively. Neural populations exhibiting these profiles are interleaved across the language network, which suggests that all language regions have direct access to distinct, multiscale representations of linguistic input-a property that may be critical for the efficiency and robustness of language processing.

Graded decisions in the human brain.

Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e., concluding in all-or-none choices), or whether the underlying representations are graded, remains unclear. To answer this question, we recorded intracranial neural signals directly from the brain while human subjects made perceptual decisions. The recordings revealed that broadband gamma activity reflecting each individual's decision-making process, ramped up gradually while being graded by the accumulated decision evidence. Crucially, this grading effect persisted throughout the decision process without ever reaching a definite bound at the time of choice. This effect was most prominent in the parietal cortex, a brain region traditionally implicated in decision-making. These results provide neural evidence for a graded decision process in humans and an analog framework for flexible choice behavior.

Proceedings of the Fourth International Workshop on Advances in Electrocorticography.

The Fourth International Workshop on Advances in Electrocorticography (ECoG) convened in New Orleans, LA, on October 11-12, 2012. The proceedings of the workshop serves as an accurate record of the most contemporary clinical and experimental work on brain surface recording and represents the insights of a unique multidisciplinary ensemble of expert clinicians and scientists. Presentations covered a broad range of topics, including innovations in passive functional mapping, increased understanding of pathologic high-frequency oscillations, evolving sensor technologies, a human trial of ECoG-driven brain-machine interface, as well as fresh insights into brain electrical stimulation.

Passive functional mapping of receptive language cortex during general anesthesia using electrocorticography.

OBJECTIVE: To investigate the feasibility of passive functional mapping in the receptive language cortex during general anesthesia using electrocorticographic (ECoG) signals. METHODS: We used subdurally placed ECoG grids to record cortical responses to speech stimuli during awake and anesthesia conditions. We identified the cortical areas with significant responses to the stimuli using the spectro-temporal consistency of the brain signal in the broadband gamma (BBG) frequency band (70-170 Hz). RESULTS: We found that ECoG BBG responses during general anesthesia effectively identify cortical regions associated with receptive language function. Our analyses demonstrated that the ability to identify receptive language cortex varies across different states and depths of anesthesia. We confirmed these results by comparing them to receptive language areas identified during the awake condition. Quantification of these results demonstrated an average sensitivity and specificity of passive language mapping during general anesthesia to be 49±7.7% and 100%, respectively. CONCLUSION: Our results demonstrate that mapping receptive language cortex in patients during general anesthesia is feasible. SIGNIFICANCE: Our proposed protocol could greatly expand the population of patients that can benefit from passive language mapping techniques, and could eliminate the risks associated with electrocortical stimulation during an awake craniotomy.

Intraoperative electrocorticography during laser-interstitial thermal therapy predicts seizure outcome in mesial temporal lobe epilepsy.

OBJECTIVE: Magnetic resonance-guided laser interstitial thermal therapy (MRLiTT) for treating temporal lobe epilepsy has recently gained popularity. We aimed to investigate the predictive value of pre-and post-MRLiTT epileptiform discharges (EDs) on intraoperative electrocorticography (iECoG) in seizure outcomes for patients with mesial temporal lobe epilepsy (mTLE). METHODS: We conducted a pilot, prospective single-center cohort study on seven consecutive patients with mTLE that underwent MRLiTT. Pre- and post-MRLiTT iECoG was performed using a 1x8 contact depth electrode along the same trajectory used for the laser catheter. RESULTS: The responders had a robust reduction in ED frequency compared to pre-MRLiTT iECoG (86% vs 13%, p < 0.01). Clinical characteristics, including risk factors for epilepsy, duration of epilepsy, presence of mesial temporal lobe sclerosis, prior intracranial monitoring, the absolute frequency of pre- or post-MRLiTT EDs, and ablation volume were not significantly associated with responder status. CONCLUSIONS: This is the first demonstration that intraoperative reduction in EDs during mesial temporal lobe MRLiTT may potentially predict seizure outcomes and may serve as an intraoperative biomarker for satisfactory ablation. However, larger prospective studies are needed to confirm our findings and evaluate the utility of iECoG during MRLiTT. SIGNIFICANCE: iECoG during mesial temporal lobe MRLiTT may help assess seizure outcomes.

Cenobamate in Generalized Epilepsy and Combined Generalized and Focal Epilepsy.

Background and Objectives: Cenobamate (CNB) is a United States Food and Drug Administration-approved antiseizure medication (ASM) for focal-onset seizures; however, its potential clinical effectiveness as a broad-spectrum ASM is not established. CNB has a proposed dual mechanism of action with preferential blockade of persistent sodium currents and positive allosteric modulation of the γ-aminobutyric acid-A (GABA-A) receptor. We evaluated the efficacy of CNB in drug refractory patients with genetic generalized epilepsies (GGE) or combined generalized and focal epilepsies (CGFE), including developmental and epileptic encephalopathies. Methods: We performed a retrospective review and identified the following: cohort 1 (n = 4) with GGE, of which 2 patients had idiopathic generalized epilepsy, and cohort 2 with CGFE (n = 9), of which 4 patients had Lennox-Gastaut syndrome and 1 had Dravet syndrome. Results: In cohort 1, all 3 patients with frequent generalized tonic-clonic seizures (GTCs) had a greater than 50% reduction in GTCs. In cohort 2, reduction in both generalized and focal-onset seizures was noted. In these groups together, the mean reduction of all seizure types was 58%, and ≥50% responder rate was 70% (SD = ±34.16, median = 50%). No worsening of generalized-onset seizures occurred in either cohort. Seventy-seven percent of patients experienced side effects, warranting a modification of treatment managed by slower titration, dose reduction of CNB, or discontinuing other ASMs. Discussion: In our retrospective case series, CNB seems to be an effective ASM for patients with drug-resistant GGE and CGFE. The ongoing CNB trial assessing effectiveness for primary GTCs will provide more data on generalized-onset seizures. Classification of Evidence: This study provides Class IV evidence that CNB in generalized epilepsy and combined generalized and focal epilepsy reduces seizure frequency.

Decoding covert spatial attention using electrocorticographic (ECoG) signals in humans.

This study shows that electrocorticographic (ECoG) signals recorded from the surface of the brain provide detailed information about shifting of visual attention and its directional orientation in humans. ECoG allows for the identification of the cortical areas and time periods that hold the most information about covert attentional shifts. Our results suggest a transient distributed fronto-parietal mechanism for orienting of attention that is represented by different physiological processes. This neural mechanism encodes not only whether or not a subject shifts their attention to a location, but also the locus of attention. This work contributes to our understanding of the electrophysiological representation of attention in humans. It may also eventually lead to brain-computer interfaces (BCIs) that optimize user interaction with their surroundings or that allow people to communicate choices simply by shifting attention to them.

Proceedings of the Third International Workshop on Advances in Electrocorticography.

The Third International Workshop on Advances in Electrocorticography (ECoG) was convened in Washington, DC, on November 10-11, 2011. As in prior meetings, a true multidisciplinary fusion of clinicians, scientists, and engineers from many disciplines gathered to summarize contemporary experiences in brain surface recordings. The proceedings of this meeting serve as evidence of a very robust and transformative field but will yet again require revision to incorporate the advances that the following year will surely bring.

A neural population selective for song in human auditory cortex.

How is music represented in the brain? While neuroimaging has revealed some spatial segregation between responses to music versus other sounds, little is known about the neural code for music itself. To address this question, we developed a method to infer canonical response components of human auditory cortex using intracranial responses to natural sounds, and further used the superior coverage of fMRI to map their spatial distribution. The inferred components replicated many prior findings, including distinct neural selectivity for speech and music, but also revealed a novel component that responded nearly exclusively to music with singing. Song selectivity was not explainable by standard acoustic features, was located near speech- and music-selective responses, and was also evident in individual electrodes. These results suggest that representations of music are fractionated into subpopulations selective for different types of music, one of which is specialized for the analysis of song.

Proceedings of the Second International Workshop on Advances in Electrocorticography.

The Second International Workshop on Advances in Electrocorticography (ECoG) was convened in San Diego, CA, USA, on November 11-12, 2010. Between this meeting and the inaugural 2009 event, a much clearer picture has been emerging of cortical ECoG physiology and its relationship to local field potentials and single-cell recordings. Innovations in material engineering are advancing the goal of a stable long-term recording interface. Continued evolution of ECoG-driven brain-computer interface technology is determining innovation in neuroprosthetics. Improvements in instrumentation and statistical methodologies continue to elucidate ECoG correlates of normal human function as well as the ictal state. This proceedings document summarizes the current status of this rapidly evolving field.

Edge-enhancing gradient echo with multi-image co-registration and averaging (EDGE-MICRA) for targeting thalamic centromedian and parafascicular nuclei.

BACKGROUND AND PURPOSE: Deep brain stimulation of the thalamus is an effective treatment for multiple neurological disorders. The centromedian and parafascicular nuclei are recently emerging targets for multiple conditions, such as epilepsy and Tourette syndrome; however, their limited visibility on conventional magnetic resonance imaging sequences has been a major obstacle. The goal of this study was to demonstrate the feasibility of a high-resolution and high-contrast targeting sequence for centromedian-parafascicular deep brain stimulation using a recently described magnetic resonance imaging sequence, three-dimensional edge-enhancing gradient echo. METHODS: The three-dimensional edge-enhancing gradient echo sequence was performed on a normal volunteer for a total of six acquisitions. Multi-image co-registration and averaging was performed by first co-registering each of the six scans and then averaging to produce an edge-enhancing gradient echo-multi-image co-registration and averaging scan. The averaging was also performed for two, three, four and five scans to assess the change in the signal-to-noise ratio and identify the ideal balance of image quality and scan time. RESULTS: The edge-enhancing gradient echo-multi-image co-registration and averaging scan allowed clear boundary delineation of the centromedian and parafascicular nuclei. The signal-to-noise ratio increased as a function of increasing scan number, but the added gain was small beyond four scans for the imaging parameters used in this study. CONCLUSIONS: The recently described three-dimensional edge-enhancing gradient echo sequence provides an easily implementable approach, using widely available magnetic resonance imaging technology without complex post-processing techniques, to delineate centromedian and parafascicular nuclei for deep brain stimulation targeting.