Surgical complications of vagus nerve stimulation surgery: A 14-years single-center experience.

Introduction: Vagus nerve stimulation (VNS) is the most frequently used neuromodulation treatment for Drug-Resistant Epilepsy (DRE) patients. Complications of VNS surgery include surgical site infection and unilateral vocal cord paresis. Complication rates vary across studies. Research question: What is the safety profile of VNS related surgeries? Materials and methods: Retrospective cohort study using patient files of DRE-patients who had undergone primary implantation of a VNS-system, replacement of the VNS pulse generator, replacement of the lead, replacement of both pulse generator and lead, or VNS removal surgery in the Maastricht UMC+. Multiple Imputation was used for missing data. Univariable and multivariable logistic regression analysis were performed to analyze possible risk factors, in case of a small sample size, an independent-samples t-test and Fisher's exact test or Pearson's X2-test were used. The complication rate was calculated as percentage. Results: This study included a total of 606 VNS surgical procedures, leading to 67 complications of which 3 permanent complications. Complication rate after primary implantation was 13.4%; 2,5% for pulse generator replacement; 21.4% for lead revision and 27.3% for complete VNS removal. No statistically significant results were found when analyzing the results of adults and children <18 years separately. Discussion and conclusion: Complication rates of VNS-related surgeries in our own institutional series are low and comparable to previously reported series. VNS surgery is a relatively safe procedure. The complication rate differs per type of surgery and mean surgery duration was longer for patients with complications after lead revision surgery compared to patients without complications.

Antibodies Contributing to Focal Epilepsy Signs and Symptoms Score.

OBJECTIVE: Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology, and to create a score to preselect patients requiring testing. METHODS: In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic. RESULTS: We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2-18). Twenty patients (3.4%) had AES, of whom 3 had anti-leucine-rich glioma inactivated 1, 3 had anti-contactin-associated protein-like 2, 1 had anti-N-methyl-D-aspartate receptor, and 13 had anti-glutamic acid decarboxylase 65 (enzyme-linked immunosorbent assay concentrations >10,000IU/ml). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% confidence interval [CI] = 19.6-3332.2, p < 0.0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1-56.6, p = 0.0005), behavioral changes (OR 12.3, 95% CI = 3.2-49.9, p = 0.0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1-56.6, p = 0.0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4-382.7, p = 0.009), and speech problems (OR = 9.6, 95% CI = 2.0-46.7, p = 0.005). The internally validated C statistic was 0.95, and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥ 2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%. INTERPRETATION: Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing. ANN NEUROL 2021;89:698-710.

Combining Gamma With Alpha and Beta Power Modulation for Enhanced Cortical Mapping in Patients With Focal Epilepsy.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55-200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8-12 Hz) and beta (15-25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22-48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient's degree of attention to the stimulus. We show that diagnostic ability can be increased by 3-5% by combining gamma and alpha and by 7.5-11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.

Assessing the effectiveness of perioperative s-ketamine on new-onset headache after resective epilepsy surgery (ESPAIN-trial): protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Effective treatment of new-onset headache after craniotomy, especially anterior temporal lobectomy (ATL) and amygdalohippocampectomy for drug-resistant temporal lobe epilepsy, is a challenge. The current practice, acetaminophen combined with opioids is often reported by patients as insufficient and sometimes accompanied by opioid-related adverse effects. Based on expert opinion, anaesthesiologists therefore frequently consider s-ketamine as add-on therapy. This randomised parallel group design trial compares s-ketamine with a placebo as add on medication to a multimodal pain approach. METHODS AND ANALYSIS: In total 62 adult participants, undergoing ATL for drug resistant epilepsy under general anaesthesia, will be randomised to either receive a 0.25 mg/kg bolus followed by a continuous infusion of 0.1 mg/kg/hour of s-ketamine or placebo (0.9% NaCl) starting before incision and continued for 48 hours as an addition to acetaminophen and opioids administered in a patient-controlled analgesia pump. The primary outcome measure is the cumulative postoperative opioid consumption. Patient recruitment started August 2018 and will end in 2021. Secondary outcome measures are postoperative pain intensity scores, psychological parameters, length of hospital stay and adverse events and will be reassessed at 3 and 6 months after surgery, with a baseline measurement preoperatively. All data are collected by researchers who are blinded to the treatment. The data will be analysed by multivariable linear mixed-effects regression. ETHICS AND DISSEMINATION: Ethical approval has been given by the local medical ethical committee (NL61666.068.17). This study will be conducted in accordance with the Dutch Medical Research Involving Human Subjects Act and the Declaration of Helsinki. The results of this trial will be publicly disclosed and submitted for publication in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NTR6480.

Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis.

OBJECTIVE: This nationwide cohort study evaluates seizure responses to immunotherapy and antiepileptic drugs (AEDs) in patients with anti-leucine-rich glioma-inactivated 1 (LGI1), anti-NMDA receptor (NMDAR), and anti-gamma-aminobutyric-acid B receptor (GABABR) encephalitis. METHODS: Anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis patients with new-onset seizures were included. Medical information about disease course, AEDs and immunotherapies used, effects, and side effects were collected. Outcome measures were (1) seizure freedom while using AEDs or immunotherapy, (2) days to seizure freedom from start of AEDs or immunotherapy, and (3) side effects. RESULTS: Of 153 patients with autoimmune encephalitis (AIE) (53 LGI1, 75 NMDAR, 25 GABABR), 72% (n = 110) had epileptic seizures, and 89% reached seizure freedom. At least 53% achieved seizure freedom shortly after immunotherapy, and 14% achieved seizure freedom while using only AEDs (p < 0.0001). This effect was similar in all types (p = 0.0001; p = 0.0005; p = 0.013, respectively). Median time to seizure freedom from AEDs start was 59 days (interquartile range [IQR] 27-160), and 28 days from start of immunotherapy (IQR 9-71, p < 0.0001). Side effects were psychotic behavior and suicidal thoughts by the use of levetiracetam, and rash by the use of carbamazepine. Carbamazepine was more effective than levetiracetam in reducing seizures in anti-LGI1 encephalitis (p = 0.031). Only 1 patient, of 86 surviving patients, developed epilepsy after resolved encephalitis. CONCLUSION: Epilepsy after resolved encephalitis was rare in our cohort of patients with AIE treated with immunotherapy. In addition, seizure freedom is achieved faster and more frequently after immunotherapy. Therefore, AEDs should be considered as add-on treatment, and similar to treatment of other encephalitis symptoms, immunotherapy is crucial.

Single-Cell Recordings to Target the Anterior Nucleus of the Thalamus in Deep Brain Stimulation for Patients with Refractory Epilepsy.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising treatment for patients with refractory epilepsy. However, therapy response varies and precise positioning of the DBS lead is potentially essential for maximizing therapeutic efficacy. We investigate if single-cell recordings acquired by microelectrode recordings can aid targeting of the ANT during surgery and hypothesize that the neuronal firing properties of the target region relate to clinical outcome. We prospectively included 10 refractory epilepsy patients and performed microelectrode recordings under general anesthesia to identify the change in neuronal signals when approaching and transecting the ANT. The neuronal firing properties of the target region, anatomical locations of microelectrode recordings and active contact positions of the DBS lead along the recorded trajectory were compared between responders and nonresponders to DBS. We obtained 19 sets of recordings from 10 patients (five responders and five nonresponders). Amongst the 403 neurons detected, 365 (90.6%) were classified as bursty. Entry into the ANT was characterized by an increase in firing rate while exit of the ANT was characterized by a decrease in firing rate. Comparing the trajectories of responders to nonresponders, we found differences neither in the neuronal firing properties themselves nor in their locations relative to the position of the active contact. Single-cell firing rate acquired by microelectrode recordings under general anesthesia can thus aid targeting of the ANT during surgery, but is not related to clinical outcome in DBS for patients with refractory epilepsy.

Acute Hospital Admissions Because of Health Care-Related Adverse Events: A Retrospective Study of 5 Specialist Departments.

BACKGROUND: Health care-related adverse events (HCRAEs), which should not be confused with (blameworthy) medical errors, are common; they can lead to hospital admissions and can have grave consequences. Although they are sometimes potentially preventable, information is lacking on HCRAEs leading to admission to different departments. AIM: This study aimed to gain insight into the incidence, type, severity, and preventability of HCRAEs (including adverse drug events) leading to hospitalization to the departments of internal medicine, surgery, orthopedics, neurology, and neurosurgery. Further, we explore if there are differences regarding these HCRAEs between these departments. METHODS: We retrospectively evaluated the medical records of all patients admitted through the emergency department (ED) in a 6-month period to the departments of internal medicine, surgery, orthopedics, neurology, and neurosurgery. All patients admitted because of HCRAEs were included. RESULTS: More than one-fifth (21.8%; range 12.0%-47.8%) of all admissions to the 5 departments were due to a HCRAE. Half (49.9%) of these HCRAEs were medication-related and 30.5% were procedure-related. In 6.5% of patients, the HCRAE led to permanent disability and another 4.4% of patients died during hospitalization. HCRAEs treated by internists and neurologists were usually medication-related, whereas HCRAEs treated by surgeons, orthopedic surgeons, and neurosurgeons were usually procedure-related. CONCLUSION: Hospital admissions to different departments are often caused by HCRAEs, which sometimes lead to permanent disability or even death. Gaining insight into similarities and differences in HCRAEs occurring in different specialties is a starting point for improving clinical outcomes.

Endothelial activation in lacunar stroke subtypes.

BACKGROUND AND PURPOSE: Lacunar stroke (LS) can be subtyped according to the absence (isolated lacunar infarct [ILA]) or presence of concomitant white matter lesions (WML) and/or asymptomatic lacunar infarcts. Endothelial activation is thought to play a pivotal role in the subtype with WML and/or asymptomatic lacunar infarcts. The aim of this study was to evaluate whether endothelial activation is associated with WML and/or asymptomatic lacunar infarcts in LS patients. Here, we determined levels of circulating blood markers of endothelial function in LS patients. METHODS: In 149 patients, all of whom had brain-MRI, levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA-PAI-1 complex, von Willebrand factor, tissue factor, thrombomodulin, and coagulation factor VIII were determined. Levels of blood markers were related to subtypes of LS and adjusted for age, gender, and vascular risk factors. RESULTS: In subtypes of LS, tPA activity was increased in patients with WML (0.79 IU/mL vs 0.44 IU/mL for ILA; P=0.02) and PAI-1-antigen levels were lowest in patients with WML (27.5 ng/mL vs 44.0 ng/mL for ILA; P=0.02). The association between WML and PAI-1 remained significant after multivariable analysis (OR, 0.99; 95% CI, 0.98-1.00 per ng/mL change of PAI-1; P=0.04). CONCLUSIONS: We found further evidence for the hypothesis of endothelial activation in the subtype of LS caused by a diffuse small vessel vasculopathy, as we found higher levels of tPA in patients with concomitant extensive WML than in those with ILA. Second, low levels of PAI-1 were associated with WML. We postulate that differences in activity of components of the fibrinolytic system might contribute to WML development.