Medically Refractory Epilepsy Research Articles

145 Encoding Brain Dynamics: Neuropsychological Test Scores as Predictors of iEEG Spectral Features in Epilepsy

INTRODUCTION: Intracranial EEG is a valuable tool for investigating the neural mechanisms underlying medically refractory epilepsy (MRE). Despite the advances made in understanding the condition, there is a lack of research exploring the relationship between iEEG data and neuropsychological test performance in MRE patients. METHODS: We performed a retrospective analysis of resting-state iEEG data from 70 MRE patients, extracting spectral features from 4.4 million 10-second time windows across 5201 electrodes. Using MATLAB and FieldTrip toolbox, we processed the data and used two brain atlases for probabilistic electrode assignment. Neuropsychological test scores were corrected for demographic factors. Relationships between preoperative neuropsychological test scores and spectral features were explored using nested hierarchical generalized linear mixed effects (GLME) models, focusing on the hippocampus. RESULTS: We found significant associations between neuropsychological tests and hippocampal power spectral densities (PSDs). Rey Auditory verbal learning test (RAVLT) recognition correct and short-term retention percentages were significantly associated with relative power (RP) in the beta-range (p < 0.05, FDR-corrected). The Boston naming test and Trail Making Test (TMT)-A finishing time showed significant associations with high-beta/low-gamma PSD (p < 0.05, FDR-corrected). TMT-B errors are positively correlated with delta/theta RP (p < 0.05, FDR-corrected). CONCLUSIONS: Our study provides novel insights into the relationship between iEEG spectral features and neuropsychological test performance in MRE patients. The findings suggest that the heterogeneity in spectral features may explain relevant cognitive performance, highlighting the biological basis and circuits of neuropsychological testing.

Surveying neurologist perspectives and knowledge of epilepsy surgery to identify barriers to surgery referral.

Epilepsy surgery is an effective means of treating medically refractory epilepsy (MRE), but it remains underused. We aimed to analyze the perspectives and knowledge of referring neurologists in the New York metropolitan area, who serve a large epilepsy population. We adapted a previous Canadian survey by Roberts etal. (2015), adding questions regarding demographic descriptors, insurance coverage, training and practice details, and perceived social barriers for patients. We surveyed neurologists directly affiliated with Montefiore Medical Center and those referring to Montefiore's Comprehensive Epilepsy Center. Participants had 10 weeks to fill out an online Qualtrics survey with weekly reminders. Of 117 neurologists contacted, 51 eligible neurologists completed the survey (63.8% Montefiore, 35.0% referring group). A high proportion of the results were from epilepsy-trained individuals (41.2%) and neurologists who graduated residency ≤19 years ago (80.4%). 80.4% of respondents felt that epilepsy surgery is safe, but only 56.9% would refer a patient for surgical workup after two failed trials of anti-seizure medications. Epileptologists and providers with a larger volume of epilepsy patients and electroencephalogram readings had better knowledge of the epilepsy surgery workup guidelines. When asked to rank social barriers to patients receiving surgery, participants were most concerned about lack of social support, financial insecurity, and a patient's dual role as a caregiver. Our study suggests continued reluctance of neurologists regarding epilepsy surgery, and deficiencies in the knowledge and adherence to the recommended guidelines. In the context of prior studies, these results showed improved understanding of the definition of MRE (80.4%) and an increased likelihood to refer eligible patients as early as possible (78.4%) in line with current consensus recommendations. The finding that epilepsy-trained and more epilepsy/electroencephalogram-facing neurologists showed better understanding of the guidelines suggests that increased education efforts should be targeted at non-epileptologists. Our study asked New York City doctors about their approach to epilepsy surgery. Many do not consider it as early as they could in treatment plans. The doctors with extra epilepsy training were better at knowing when to consider surgery.

The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment.

Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume. High-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses. Glioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells. High-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.

Predictors of clinically significant anhedonia in refractory epilepsy

Background: Anhedonia, the inability to feel pleasure or motivation for reward, is a core feature of depression in epilepsy, but can occur independent from depression. It is reported in over a third of people with epilepsy and has a significant impact on quality of life. Objectives: This study determined whether specific features of medication refractory epilepsy are predictive of anhedonia. Design: We assessed 267 patients with medication refractory epilepsy for anhedonia, primarily using the clinically validated Snaith-Hamilton Pleasure Scale (SHAPS) scale. Methods: Patients with clinically significant anhedonia were compared with those without for key demographics, epilepsy characteristics and medication using a logistic regression analysis. Results: We found that seizure frequency (p < 0.01) but not duration of epilepsy was significantly associated with anhedonia. We also found that benzodiazepine use was significantly associated (p = 0.01) with anhedonia, and levetiracetam/brivaracetam and sodium valproate were significantly negatively associated with anhedonia (0.01 and 0.03 respectively). Conclusion: High seizure burden in medication refractory epilepsy is significantly associated with anhedonia. Specific antiseizure medications are also associated with the development of anhedonia, but it is unclear whether their use is causative or influenced by the presence of anhedonia.

Robotic-Assisted Stereoelectroencephalography: A Systematic Review and Meta-Analysis of Safety, Outcomes, and Precision in Refractory Epilepsy Patients.

Robotic assistance in stereoelectroencephalography (SEEG) holds promising potential for enhancing accuracy, efficiency, and safety during electrode placement and surgical procedures. This systematic review and meta-analysis, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration, delves into the latest advancements and implications of robotic systems in SEEG, while meticulously evaluating outcomes and safety measures. Among 855 patients suffering from medication-refractory epilepsy who underwent SEEG in 29 studies, averaging 24.6 years in age, the most prevalent robots employed were robotic surgical assistant (ROSA) (450 patients), Neuromate (207), Sinovation (140), and ISys1 (58). A total of 8,184 electrodes were successfully implanted, with an average operative time of 157.2 minutes per procedure and 15.1 minutes per electrode, resulting in an overall mean operative time of 157.7 minutes across all studies. Notably, the mean target point error (TPE) stood at 2.13 mm, the mean entry point error (EPE) at 1.48 mm, and postoperative complications occurred in 7.69% of robotically assisted (RA) SEEG cases (60), with 85% of these complications being asymptomatic. This comprehensive analysis underscores the safety and efficacy of RA-SEEG in patients with medication-refractory epilepsy, characterized by low complication rates, reduced operative time, and precise electrode placement, supporting its widespread adoption in clinical practice, with no discernible differences noted among the various robotic systems.

Hemispherectomy Outcome Prediction Scale: a validity study.

Hemispherectomy is highly effective for patients with medically refractory epilepsy (MRE) arising from a single hemisphere. Recently, the Hemispherectomy Outcome Prediction Scale (HOPS) was developed as a prediction tool for seizure freedom after hemispherectomy. The authors' goal was to perform a validation study to determine the generalizability of the HOPS score. The authors present an observational, retrospective, 20-year, single-institution, two-surgeon experience using the lateral peri-insular hemispherectomy approach to validate the HOPS score. Variables used to derive the HOPS score included seizure onset age, semiology, PET hypometabolism, seizure substrate, and history of prior epilepsy resection. Multivariable logistic regression, multiple imputation, and Bayesian analyses were used to determine validity. The authors' cohort comprised 60 patients; 55% of patients were male and 78% were Caucasian. The median age at first hemispherectomy surgery was 72 months. At 1 year postoperatively, 80% of patients had Engel class I outcomes, analogous to most contemporary series. All patients who experienced seizure recurrence after hemispherectomy did so within the first 2 years postoperatively. Sixteen (27%) and 10 (17%) patients had contralateral MRI findings and hypometabolism on PET, respectively. Both a multivariable logistic regression model using HOPS score variables (model p = 0.2588) and a revised model that included contralateral MRI findings (model p = 0.4715) were not statistically significant in this cohort. Bayesian analysis also did not validate the HOPS score. While seizure outcome prediction tools may be helpful for counseling patients about postoperative outcomes, rigorous validity and reliability testing are required. Prospective, standardized, and longitudinal evaluation of patients undergoing hemispherectomy are needed.

Pediatric vagal nerve stimulator explantation: A comprehensive literature review and tertiary care experience.

Patients with medically-refractory epilepsy who undergo vagal nerve stimulator (VNS) implantation to reduce seizure burden sometimes require device removal. Complete explantation refers to the removal of both the generator and vagal nerve leads, and is uncommonly performed by otolaryngologists due to the perceived risk associated with lead removal. This comprehensive literature review and case series studies safety outcomes among pediatric patients undergoing complete VNS explantation. Literature review and tertiary care case series. PubMed, Embase, Web of Science, and Google Scholar were searched to identify all articles involving VNS explantation prior to January 2023. A retrospective review of pediatric patients undergoing complete VNS explantation from 2009 to 2023at our tertiary center was also conducted. After screening, 36 articles were retained involving 399 patients (139 confirmed children) who underwent complete VNS explantation. 26 patients (6.5%) experienced 1+ peri/post-operative complications. These included temporary VF paresis or dysphonia (n=14; 3.6%), permanent vocal fold (VF) paralysis/paresis (n=6; 1.5%), internal jugular vein injury (n=4; 1.0%), temporary dysphagia (n=2; 0.50%), and cable-bowstring phenomenon (n=1; 0.25%). Data from our tertiary care center revealed eight patients (6M: 2F) with a mean age of 11.4±6.2 years. Devices were removed for clinical ineffectiveness (n=2), infection (n=2), lead failures (n=2), and increased lead impedance (n=2). Mean total length of implantation was 44.4±40.3 months. Mean follow-up was 44.8±35.2 months. No complications were identified. Complete VNS device removal in pediatric patients is technically feasible with low reported complications. Working alongside neurosurgery, otolaryngologists offer unique expertise in dissection along the vagus nerve and may thus add value to the practice of VNS surgery.

Postoperative seizure freedom after vagus nerve stimulator placement in children 6 years of age and younger.

Food and Drug Administration (FDA) approval for vagus nerve stimulator (VNS) implantation is limited to patients older than 4 years of age with medically refractory partial-onset seizures. In younger children with severe generalized epilepsy, however, VNS implantation remains off-label. In this study, the authors followed up on their previously reported cohort to review the longer-term safety and efficacy of VNS placement in children younger than 6 years with generalized medically refractory epilepsy (MRE), providing the largest cohort with > 2 years of follow-up to date in this age group. This was a retrospective observational cohort study of patients younger than 6 years of age with generalized MRE who underwent VNS implantation at a single institution between 2010 and 2020. Inclusion criteria encompassed failure of more than two antiepileptic drugs alone or in combination, neurologist referral for vagus nerve stimulation, informed consent with knowledge of the off-label status in young children, and > 1 year of follow-up. Outcome measures included seizure reduction rate ≥ 50% and postoperative morbidity defined nominally. Statistical analysis was conducted with Stata/SE. Forty-five patients were included: 11 patients younger than 4 years of age and 34 between 4 and 6 years of age. There were no intraoperative complications. Perioperative complications within 1 year occurred in 11% (n = 5) of the patients and included two wound infections, a mild cough, hyperactivity, hoarseness, and 1 patient with persistent surgical site pain. A seizure reduction ≥ 50% was observed in 36.4% (n = 4) of the patients younger than 4 years of age at the 6-month and 1-, 2-, and 5-year follow-ups. In the 4- to 6-year-old cohort, this was observed in 32.4% (n = 11) of the patients at 6 months, 41.2% (n = 14) at 1 year, 38.2% (n = 13) at 2 years, and 41.2% (n = 14) at 5 years. VNS implantation for patients younger than 4 years of age with generalized onset MRE has not been approved by the FDA. This retrospective study establishes feasibility, illustrates an acceptable safety profile in children younger than 6 years, and demonstrates efficacy comparable to that reported in older patients.

Stereoelectroencephalography followed by combined electrode removal and MRI-guided laser interstitial thermal therapy or open resection: a single-center series in pediatric patients with medically refractory epilepsy.

Stereoelectroencephalography (SEEG) and MRI-guided laser interstitial thermal therapy (MRgLITT) have emerged as safe, effective, and less invasive alternatives to subdural grid placement and open resection, respectively, for the localization and treatment of medically refractory epilepsy (MRE) in children. Reported pediatric experience combining these complementary techniques is limited, with traditional workflows separating electrode removal and ablation/resection. The authors describe the largest reported series of pediatric epilepsy patients who underwent MRgLITT following SEEG contrasted with a cohort that underwent craniotomy following SEEG, combining ablation/resection with electrode explantation as standard practice. The medical records of all patients with MRE who had undergone SEEG followed by MRgLITT or open resection/disconnection at Boston Children's Hospital between November 2015 and December 2020 were retrospectively reviewed. Primary outcome variables included surgical complication rates, length of hospital stay following treatment, and Engel classification at the last follow-up. Of 74 SEEG patients, 27 (median age 12.1 years, 63% female) underwent MRgLITT and 47 (median age 12.1 years, 49% female) underwent craniotomy. Seventy patients (95%) underwent SEEG followed by combined electrode removal and treatment. Eight MRgLITT cases (30%) and no open cases targeted the insula (p < 0.001). Complication rates did not differ, although trends toward more subdural/epidural hematomas, infarcts, and permanent unanticipated neurological deficits were evident following craniotomy, whereas a trend toward more temporary unanticipated neurological deficits was seen following MRgLITT. The median duration of hospitalization after treatment was 3 and 5 days for MRgLITT and open cases, respectively (p = 0.078). Seizure outcomes were similar between the cohorts, with 74% of MRgLITT and craniotomy patients attaining Engel class I or II outcomes (p = 0.386) at the last follow-up (median 1.1 and 1.9 years, respectively). MRgLITT and open resection following SEEG can both effectively treat MRE in pediatric patients and generally can be performed in a two-surgery workflow during a single hospitalization. In appropriately selected patients, MRgLITT tended to be associated with shorter hospitalizations and fewer complications following treatment and may be best suited for focal deep-seated targets associated with relatively challenging open surgical approaches.

Trans-Interhemispheric Stereoelectroencephalography Depth Electrode Placement for Mesial Frontal Lobe Explorations in Medically Refractory Epilepsy: A Technical Note and Case Series.

Stereoelectroencephalography (SEEG) is an established and safe methodology for extra-operative invasive monitoring in patients with medical refractory epilepsy. SEEG has several advantages such as the ability to record deep cortical structures, mapping the epileptogenic zone in a three-dimensional manner, and analyze bihemispheric regions without the need for bilateral craniotomies. In patients with bilateral hemispheric hypotheses, especially the mesial surface of frontal lobes, bilateral lead placement is compulsory to further define and localize the epileptogenic zone. In this particular cohort of patients, bilateral monitoring may be accomplished from a single entry point using trans-interhemispheric placement of the electrodes. The use of trans-interhemispheric monitoring offers several advantages including sparing the need for additional leads. To test the hypothesis that, given the lack of the falx as a limiting structure in the ventral and mesial frontal lobe regions, trans-interhemispheric SEEG placement is feasible and a potential benefit for the SEEG method. We report on 6 patients who underwent bilateral monitoring using trans-interhemispheric SEEG lead placement and discuss the operative technique. Six patients underwent trans-interhemispheric monitoring, with a median of 3 leads per patient (19 total). Trajectory error was minimal (<0.3 mm), and operating room time was comparable with that in previous reports. All leads were placed without adverse events, mislocalization, electrode hemorrhages, or any other complications. All patients had successful localization of the epileptogenic zone. Trans-interhemispheric SEEG to monitor the mesial wall of frontal lobe regions is technically feasible. No adverse events were observed, suggesting a favorable safety profile.

DeepEZ: A Graph Convolutional Network for Automated Epileptogenic Zone Localization From Resting-State fMRI Connectivity.

Epileptogenic zone (EZ) localization is a crucial step during diagnostic work up and therapeutic planning in medication refractory epilepsy. In this paper, we present the first deep learning approach to localize the EZ based on resting-state fMRI (rs-fMRI) data. Our network, called DeepEZ, uses a cascade of graph convolutions that emphasize signal propagation along expected anatomical pathways. We also integrate domain-specific information, such as an asymmetry term on the predicted EZ and a learned subject-specific bias to mitigate environmental confounds. We validate DeepEZ on rs-fMRI collected from 14 patients with focal epilepsy at the University of Wisconsin Madison. Using cross validation, we demonstrate that DeepEZ achieves consistently high EZ localization performance (Accuracy: 0.88 ± 0.03; AUC: 0.73 ± 0.03) that far outstripped any of the baseline methods. This performance is notable given the variability in EZ locations and scanner type across the cohort. Our results highlight the promise of using DeepEZ as an accurate and noninvasive therapeutic planning tool for medication refractory epilepsy. While prior work in EZ localization focused on identifying localized aberrant signatures, there is growing evidence that epileptic seizures affect inter-regional connectivity in the brain. DeepEZ allows clinicians to harness this information from noninvasive imaging that can easily be integrated into the existing clinical workflow.

Decision-making in stereotactic epilepsy surgery.

Surgery can cure or significantly improve both the frequency and the intensity of seizures in patients with medication-refractory epilepsy. The set of diagnostic and therapeutic interventions involved in the path from initial consultation to definitive surgery is complex and includes a multidisciplinary team of neurologists, neurosurgeons, neuroradiologists, and neuropsychologists, supported by a very large epilepsy-dedicated clinical architecture. In recent years, new practices and technologies have emerged that dramatically expand the scope of interventions performed. Stereoelectroencephalography has become widely adopted for seizure localization; stereotactic laser ablation has enabled more focal, less invasive, and less destructive interventions; and new brain stimulation devices have unlocked treatment of eloquent foci and multifocal onset etiologies. This article articulates and illustrates the full framework for how epilepsy patients are considered for surgical intervention, with particular attention given to stereotactic approaches.

SAMCOR: A robust and precise co-registration algorithm for brain CT and MR imaging

ObjectiveCurrent methods for co-registration of computed tomography (CT) and magnetic resonance (MR) brain imaging employ optimization-based cost functions of advanced statistical metrics to align datasets (e.g. mutual information, MI). Yet the inherent differences between these modalities still lead to occasional failures of registration. To address these limitations, we developed a novel approached termed sequence adaptive multimodal co-registration (SAMCOR), which is robust to intensity, feature, and scanner-based differences. MethodsSAMCOR was validated using 152 CT and MRI datasets from subjects implanted with intracranial electrodes for evaluation of medically-refractory epilepsy. Alignment outcomes were compared against five current open-source co-registration algorithms and a widely used commercial neurosurgical navigation system and classified as aligned/not-aligned relative to manually co-registered datasets. ResultsSAMCOR was the only method to align all 152 datasets (100%), while success rates for existing algorithms ranged from 3% to 82%. Given the time-intensive nature of manual verification, we further developed a metric to automatically quantify co-registration accuracy using Dice Similarity Coefficients (DSC). We applied a binary classification analysis to evaluate this DSC metric performance against traditional mutual information (MI) metrics for predicting alignment outcomes. The DSC metric demonstrated significantly higher positive and negative predictive values (0.93 and 0.97, respectively) than MI (0.79 and 0.87, respectively). The DSC classifier accuracy was 94.7% (vs 83.2% for MI). ConclusionsOur novel approaches for CT-MRI co-registration and quantitative alignment outcome analysis demonstrate significant advancements of the state-of-the-art for intermodal image co-registration with clinical relevance in patients with implanted intracranial devices.

Imaging in medically refractory epilepsy at 3 Tesla: a 13-year tertiary adult epilepsy center experience

ObjectivesMRI negative epilepsy has evolved through increased usage of 3 T and insights from surgically correlated studies. The goal of this study is to describe dedicated 3 T epilepsy MRI findings in medically refractory epilepsy (MRE) patients at a tertiary epilepsy center to familiarize radiologists with an updated spectrum and frequency of potential imaging findings in the adult MRE population.MethodsIncluded were all patients with MRE admitted to the epilepsy monitoring unit who were discussed at weekly interdisciplinary imaging conferences at Toronto Western Hospital with MRI studies (3 T with dedicated epilepsy protocol) performed between January 2008 and January 2021. Lesion characterization was performed by two readers based on most likely imaging diagnosis in consensus. Lobes involved per case were recorded.ResultsA total of 738 patients (386 female; mean age 35 years, range 15–77) were included. A total of 262 patients (35.5%) were MRI negative. The most common imaging finding was mesial temporal sclerosis, seen in 132 patients (17.9%), followed by encephalomalacia and gliosis, either posttraumatic, postoperative, postischemic, or postinfectious in nature, in 79 patients (10.7%). The most common lobar involvement (either partially or uniquely) was temporal (341 cases, 58.6%). MRE patients not candidates for surgical resection were included in the study, as were newly described pathologies from surgically correlated studies revealing findings seen retrospectively on reported MRI negative exams (isolated enlargement of the amygdala, temporal pole white matter abnormality, temporal encephalocele).ConclusionThis study provides an updated description of the spectrum of 3 T MRI findings in adult MRE patients from a tertiary epilepsy center.

Dose-dependent seizure control with MEK inhibitor therapy for progressive glioma in a child with neurofibromatosis type 1

BackgroundLow-grade gliomas (LGGs) occurring in children can result in many different neurologic complications, including seizures. MEK inhibitors are increasingly being used to treat LGG, but their effect on associated neurologic symptoms has not been established.ResultsHere, we report a patient with neurofibromatosis type 1 (NF1), medically refractory epilepsy (MRE), and an extensive optic pathway glioma (OPG) who developed dose-dependent seizure control while being treated with selumetinib. Seizure frequency rebounded after dose reduction for cardiac toxicity, then improved, and finally ceased after restarting full dosing, allowing confidence in the cause of improvement.ConclusionSelumetinib may have promise in epilepsy management in other children with NF1 or LGG.

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.

Characterizing Complications of Intracranial Responsive Neurostimulation Devices for Epilepsy Through a Retrospective Analysis of the Federal MAUDE Database

ObjectivesResponsive neurostimulation is an innovative modality in the treatment of medication-refractory epilepsy for patients who are not suitable candidates for surgical intervention. While being a potentially life-changing treatment option for many individuals with epilepsy, little is known about the system's complications aside from its performance in initial clinical trials. Therefore, the goal of this study was to characterize all reported complications of the RNS system made to the Food & Drug Administration since its approval. Materials and MethodsThe Manufacturer and User Facility Device Experience (MAUDE) database was queried for entries reported under “implanted brain stimulator for epilepsy” through the dates of November 1, 2013, to March 1, 2020. After correction of duplicate entries, each was sorted into complication types based on the entries' narrative descriptions. ResultsThe searched yielded 241 unique complication events. The most common complications were attributed to infections (40%) and lead breaks (12%). Other reported complications included poor wound healing (10%) and intrinsic device failure (7%). Focal neurological deficits were found in 2%. Over half (67%) of the reported complications required return to the operating room for revision or explant. The remainder of the adverse events were self-resolved or treated with either medication or software adjustment. ConclusionsFuture research endeavors should attempt to optimize the implantable device for preventing infections. The data of complications provided by this review will also aid physicians in providing the most accurate informed consent for patients when deciding to undergo implantation with the responsive neurostimulation system.

High b-value diffusion tractography: Abnormal axonal network organization associated with medication-refractory epilepsy

Diffusion magnetic resonance imaging (dMRI) tractography has played a critical role in characterizing patterns of aberrant brain network reorganization among patients with epilepsy. However, the accuracy of dMRI tractography is hampered by the complex biophysical properties of white matter tissue. High b-value diffusion imaging overcomes this limitation by better isolating axonal pathways. In this study, we introduce tractography derived from fiber ball imaging (FBI), a high b-value approach which excludes non-axonal signals, to identify atypical neuronal networks in patients with epilepsy. Specifically, we compared network properties obtained from multiple diffusion tractography approaches (diffusion tensor imaging, diffusion kurtosis imaging, FBI) in order to assess the pathophysiological relevance of network rearrangement in medication-responsive vs. medication-refractory adults with focal epilepsy. We show that drug-resistant epilepsy is associated with increased global network segregation detected by FBI-based tractography. We propose exploring FBI as a clinically feasible alternative to quantify topological changes that could be used to track disease progression and inform on clinical outcomes.

Compassion, communication, and the perception of control: a mixed methods study to investigate patients’ perspectives on clinical practices for alleviating distress and promoting empowerment during awake craniotomies

Purpose To inquire into clinical practices perceived to mitigate patients’ intraoperative distress during awake craniotomies. Methods This mixed-methods study involved administration of Amsterdam Preoperative Anxiety and Information Scale and PTSD Checklist prior to the awake craniotomy to evaluate anxiety and information-seeking related to the procedure and symptoms of PTSD. Generalized Anxiety Disorder Scale and Depression Module of the Patient Health Questionnaire were administered before and after the procedure to evaluate generalized anxiety and depression. Patient interviews were conducted 2-weeks postprocedure and included a novel set of patient experience scales to assess patients’ recollection of intraoperative pain, overall distress, anxiety, distress due to noise, perception of empowerment, perception of being well-prepared, overall satisfaction with anaesthesia management, and overall satisfaction with the procedure. Qualitative data were analysed using conventional content analysis. Results Participants (n = 14) had undergone an awake craniotomy for tissue resection due to primary brain tumours or medically-refractory focal epilepsy. Validated self-report questionnaires demonstrated reduced levels of generalized anxiety (pre mean = 8.66; SD = 6.41; post mean= 4.36; SD = 4.24) following the awake craniotomy. Postprocedure interviews revealed very high satisfaction with the awake craniotomy and anaesthesia management and minimal levels of intraoperative pain, anxiety, and distress. The most stressful aspects of the procedure included global recognition of medical diagnosis, anxiety provoked by unfamiliar sights, sounds, and sensations, a perception of a lack of information or misinformation, and long periods of immobility. Important factors in alleviating intraoperative distress included the medical team’s ability to promote patient perceptions of control, establish compassionate relationships, address unfamiliar intraoperative sensations, and deliver effective anaesthesia management. Conclusion Compassion, communication, and patient perception of control were critical in mitigating intraoperative distress. Clinical practice recommendations with implications for all clinicians involved in patient care during awake craniotomies are provided. Use of these interventions and strategies to reduce distress are important to holistic patient care and patient experiences of care and may improve the likelihood of optimal brain mapping procedures to improve clinical outcomes during awake craniotomies.

Human organ donor-derived vagus nerve biopsies allow for well-preserved ultrastructure and high-resolution mapping of myelinated and unmyelinated fibers

The vagus nerve provides motor, sensory, and autonomic innervation of multiple organs, and electrical vagus nerve stimulation (VNS) provides an adjunctive treatment option for e.g. medication-refractory epilepsy and treatment-resistant depression. The mechanisms of action for VNS are not known, and high-resolution anatomical mapping of the human vagus nerve is needed to better understand its functional organization. Electron microscopy (EM) is required for the detection of both myelinated and unmyelinated axons, but access to well-preserved human vagus nerves for ultrastructural studies is sparse. Intact human vagus nerve samples were procured intra-operatively from deceased organ donors, and tissues were immediately immersion fixed and processed for EM. Ultrastructural studies of cervical and sub-diaphragmatic vagus nerve segments showed excellent preservation of the lamellated wall of myelin sheaths, and the axolemma of myelinated and unmyelinated fibers were intact. Microtubules, neurofilaments, and mitochondria were readily identified in the axoplasm, and the ultrastructural integrity of Schwann cell nuclei, Remak bundles, and basal lamina was also well preserved. Digital segmentation of myelinated and unmyelinated axons allowed for determination of fiber size and myelination. We propose a novel source of human vagus nerve tissues for detailed ultrastructural studies and mapping to support efforts to refine neuromodulation strategies, including VNS.