Britton, Jeffrey W.

OBJECTIVE Surgical site infection (SSI) is a rare but significant complication after vagus nerve stimulator (VNS) placement. Treatment options range from antibiotic therapy alone to hardware removal. The optimal therapeutic strategy remains open to debate. Therefore, the authors conducted this retrospective multicenter analysis to provide insight into the optimal management of VNS-related SSI (VNS-SSI). METHODS Under institutional review board approval and utilizing an institutional database with 641 patients who had undergone 808 VNS-related placement surgeries and 31 patients who had undergone VNS-related hardware removal surgeries, the authors retrospectively analyzed VNS-SSI. RESULTS Sixteen cases of VNS-SSI were identified; 12 of them had undergone the original VNS placement procedure at the authors’ institutions. Thus, the incidence of VNS-SSI was calculated as 1.5%. The mean (± standard deviation) time from the most recent VNS-related surgeries to infection was 42 (± 27) days. Methicillin-sensitive staphylococcus was the usual causative bacteria (58%). Initial treatments included antibiotics with or without nonsurgical procedures (n = 6), nonremoval open surgeries for irrigation (n = 3), generator removal (n = 3), and total or near-total removal of hardware (n = 4). Although 2 patients were successfully treated with antibiotics alone or combined with generator removal, removal of both the generator and leads was eventually required in 14 patients. Mild swallowing difficulties and hoarseness occurred in 2 patients with eventual resolution. CONCLUSIONS Removal of the VNS including electrode leads combined with antibiotic administration is the definitive treatment but has a risk of causing dysphagia. If the surgeon finds dense scarring around the vagus nerve, the prudent approach is to snip the electrode close to the nerve as opposed to attempting to unwind the lead completely.

Abstract Seizures are a well‐recognized and often prominent manifestation of autoimmune encephalitic syndromes. Progress in detection of pathogenic neural autoantibodies has led to increased awareness of autoimmune causes of seizures. Clinical studies of patients with these autoantibodies have improved our understanding of the seizure characteristics, treatments, and seizure prognosis in these disorders. The International League Against Epilepsy (ILAE) Autoimmunity and Inflammation Taskforce proposes conceptual definitions for two main diagnostic entities: (a) acute symptomatic seizures secondary to autoimmune encephalitis, and (b) autoimmune‐associated epilepsy, the latter of which suggests an enduring predisposition to seizures. Such a distinction is relevant when discussing the pathophysiology, treatment, prognosis, and social consequences of these disorders. We discuss the role of biomarkers in the application of these conceptual definitions and illustrate their use in patients cared for by members of the task force.

Introduction: Nonconvulsive seizures (NCSs) are common in critically ill adult patients with acute neurologic conditions. However, the effect of NCSs on patient outcome remains unclear. In this study, we aimed to determine the effect of NCSs on short-term outcome and to assess the clinical and EEG factors associated with NCSs. Methods: We retrospectively identified 219 adult patients from the EEG reporting system who underwent continuous EEG (cEEG) monitoring between January 2018 and June 2018. Patients with anoxic brain injury were excluded from the study. Clinical, laboratory, and EEG data were reviewed to determine potentially predictive factors of NCSs. The impact of NCSs on in-hospital mortality, length of stay, and disability on discharge was measured; an modified Rankin scale of three or greater was considered disabled. Results: Of the 219 patients included in our study, a total of 14% (n = 31) had NCSs on continuous EEG, of which 42% (n = 13) had their first seizure discharge recorded during the first hour of continuous EEG monitoring. The presence of clinical seizures before continuous EEG (odds ratio = 1.787; 95% confidence interval = 1.197–2.667, P = 0.0045), history of epilepsy (odds ratio = 1.508; 95% confidence interval = 1.027–2.215, P = 0.035), and comatose state (29 vs. 16%; P = 0.0006) were associated with NCSs. Among EEG characteristics, the presence of interictal epileptiform discharges (P < 0.0001), lateralized rhythmic delta activity (P = 0.02), and lateralized periodic discharges (P < 0.0001) were associated with NCSs. Nonconvulsive seizures were significantly associated with longer in-hospital stay (23.68 ± 24.84 vs. 17.14 ± 20.52; P = 0.036) and disability on discharge (87% [n = 27] vs. 13% [n = 4], P = 0.02). However, there was no significant association between NCS and in-hospital mortality (9.6% [n = 3] vs. 10.6% [n = 20]; P = 0.1). Conclusions: Nonconvulsive seizures are associated with longer in-hospital stay and disability on discharge but not with in-hospital mortality in adult patients.

ObjectiveDrug‐resistant seizures are common in patients with leucine‐rich, glioma‐inactivated 1 (LGI1)‐IgG associated and contactin‐associated protein‐like 2 (CASPR2)‐IgG associated encephalitis. We performed the first randomized double‐blind placebo‐controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency.MethodsOur enrollment goal was 30 LGI1/CASPR2‐IgG–seropositive adult patients with ≥2 seizures per week. Patients were randomized to receive IVIG (0.5g/kg day 1, 1g/kg day 2, 0.6g/kg weeks 3 and 5) or volume‐matched intravenous normal saline. Following the blinded phase, the nonresponders in the placebo group received IVIG. The primary clinical outcome was 50% reduction in seizure frequency from baseline to 5 weeks.ResultsAfter enrollment of 17 patients (LGI1‐IgG, 14; CASPR2‐IgG, 3) over 34 months, the study was terminated due to slow enrollment. Six of 8 patients in the IVIG group were responders, compared to 2 of 9 in the placebo group (p = 0.044, odds ratio = 10.5, 95% confidence interval = 1.1–98.9). For the LGI1‐IgG seropositive subgroup, 6 of 8 patients in the IVIG group were responders, compared to zero of 6 in the placebo group. Two LGI1‐IgG–seropositive patients receiving IVIG, but none receiving placebo, were seizure‐free at the end of the blinded phase. Four of the 6 patients entering the open‐label IVIG arm reported ≥50% reduction in seizure frequency. There were no correlations with LGI1/CASPR2‐IgG1–4 subclasses.InterpretationSuperiority of IVIG to placebo reached statistical significance for the primary endpoint for all patients and the subset with LGI1‐IgG. These results have to be interpreted with the caveat that the study did not reach its originally selected sample size. ANN NEUROL 2020;87:313–323

AbstractObjectiveTo evaluate the presence of tau deposition and pathologic features of chronic traumatic encephalopathy (CTE) in young adult patients treated with focal cortical resections for drug‐resistant epilepsy.MethodsSixty consecutive patients who had undergone surgical treatment for drug‐resistant focal epilepsy between 18 and 45 years of age were identified (2010‐2017). Medical records were reviewed to determine clinical factors, including history of head trauma, age at seizure onset, age at surgical resection, seizure type(s) and frequency, imaging findings, and surgical outcome. All formalin‐fixed, paraffin‐embedded blocks from the surgical specimens from each subject were sectioned and stained with hematoxylin and eosin and antibodies to tau (Thermo Fisher Scientific Clone AT8), and examined blindly for tau pathology, including lesions characteristic of CTE.ResultsThe median age at resection was 29.5 years (range = 19‐45). A history of head trauma was reported in 19 patients. Although none of the patients had pathological findings characteristic of CTE, 23 patients (38%) demonstrated tau‐immunoreactive lesions, including neurites, neurofibrillary pretangles, neurofibrillary tangles, subpial tau, and/or glial tau. In 4 of the 23 patients (7% of the cohort; 17% of those with tau pathology), substantial tau burden was identified. Three of these 4 patients had no significant history of head trauma; 1 patient had multiple sports‐related concussions. No specific clinical factors correlated with the presence of tau pathology.SignificanceTau‐immunoreactive lesions were found in 38% of 60 patients who underwent a focal cortical resection for drug‐resistant focal epilepsy. Diagnostic features of CTE were not detected in any patient; however, the pathological evaluation for CTE was limited to a surgical specimen. The prominent and excessive tau deposition in 23 patients (38%) is abnormal in this age group and warrants further investigation.

Objective: After-hours EEG is increasingly used in hospital patients. Although the detection of seizures and interictal epileptiform discharges has been shown to be higher with prolonged EEG (pEEG) than routine-duration EEG, the relative value for particular indications can inform utilization. Method: The Mayo EEG Report System was queried for after-hours emergent routine EEG (ErEEG) and pEEG performed between January 2015 and June 2015. Total 296 after-hours ErEEG were identified, of which 140 converted into pEEG were included in the study for direct comparison of two modalities. Indications were categorized as: mental status changes, recent seizures rule out continued nonconvulsive seizures, spells, and prognosis after anoxic brain injury. Categorical data were analyzed using the McNemar and Fisher exact tests; a P value of 0.05 was considered significant. Result: Prolonged EEG was superior to ErEEG for detection of interictal epileptiform discharges (61 vs. 48/140, P = 0.004) and seizures (29 vs. 17/140, P = 0.012). Seizure detection was greater for pEEG than ErEEG for the indication of evaluating for subclinical seizures after recent observed clinical seizures (14/41 [34.1%] versus 4/41 [9.8%], P = 0.002). There was no significant difference between modalities for seizure detection in patients undergoing evaluation of spells or mental status changes without previous observed seizures. Detection of seizures on pEEG was higher for recordings greater than 24 hours (8/46, 17%, P = 0.014) and 48 hours (19/26, 73%, P < 0.001) than recordings less than 24 hours (2/68, 3%). Seizure detection was higher with pEEG in comatose patients than ErEEG (17/51, 33% vs. 12/89, 13%; P = 0.009). Conclusions: Increased value was demonstrated for pEEG over ErEEG in patients undergoing evaluation after observed recent clinical seizures and for coma. No significant difference was found between ErEEG and pEEG for seizure detection in the relatively small subgroups of patients with mental status changes other than coma and without preceding seizure or spells.

AbstractObjectiveTo assess the frequency and characteristics of interictal and postictal headaches (using International Classification of Headache Disorders, 3rd edition criteria) in a population of patients with epilepsy admitted to the Mayo Clinic Rochester epilepsy monitoring unit and assess their localizing value.MethodsThis was a cross‐sectional study. Participants were voluntarily recruited upon admission to the epilepsy monitoring unit. Two separate questionnaires were then administered. The first was to assess the presence and character of headaches experienced in the past 12 months. The second was to assess characteristics of postictal headaches experienced during their admission including localization.ResultsOne‐hundred and twenty subjects (77%) met inclusion criteria and completed the initial questionnaire. Mean age was 38.1 years (range 18‐82), and 67 (55.8%) were female. Interictal headaches were reported in 97 of 120 (81%) subjects, and these met ICHD3 criteria for migraine in 48 (50%). Postictal headaches were reported by 75 of 120 (63%) subjects on the initial admission questionnaire, representing migraine in 38 (51%). Thirty‐nine (32%) subjects completed the secondary questionnaire related to postictal headaches experienced during admission, of which nine (23%) met criteria for migraine. There was no seizure lateralizing or localizing value noted based on postictal headache localization.SignificanceMigraine was frequent in this cohort and appears to be the dominant interictal and postictal headache type in patients with epilepsy. In this study, the first to assess incident postictal headache in the setting of an ictal EEG, headache localization was of no seizure localizing value. Few patients were being actively treated; suggesting headache management is often overlooked in the epilepsy population.

AbstractObjectiveTo rigorously compare automated atlas‐based and manual tracing hippocampal segmentation for accuracy, repeatability, and clinical acceptability given a relevant range of imaging abnormalities in clinical epilepsy.MethodsForty‐nine patients with hippocampal asymmetry were identified from our institutional radiology database, including two patients with significant anatomic deformations. Manual hippocampal tracing was performed by experienced technologists on 3T MPRAGE images, measuring hippocampal volume up to the tectal plate, excluding the hippocampal tail. The same images were processed using NeuroQuant and FreeSurfer software. Ten subjects underwent repeated manual hippocampal tracings by two additional technologists blinded to previous results to evaluate consistency. Ten patients with two clinical MRI studies had volume measurements repeated using NeuroQuant and FreeSurfer.ResultsFreeSurfer raw volumes were significantly lower than NeuroQuant (P < 0.001, right and left), and hippocampal asymmetry estimates were lower for both automatic methods than manual tracing (P < 0.0001). Differences remained significant after scaling volumes to age, gender, and scanner matched normative percentiles. Volume reproducibility was fair (0.4–0.59) for manual tracing, and excellent (>0.75) for both automated methods. Asymmetry index reproducibility was excellent (>0.75) for manual tracing and FreeSurfer segmentation and fair (0.4–0.59) for NeuroQuant segmentation. Both automatic segmentation methods failed on the two cases with anatomic deformations. Segmentation errors were visually identified in 25 NeuroQuant and 27 FreeSurfer segmentations, and nine (18%) NeuroQuant and six (12%) FreeSurfer errors were judged clinically significant.InterpretationAutomated hippocampal volumes are more reproducible than hand‐traced hippocampal volumes. However, these methods fail in some cases, and significant segmentation errors can occur.

Abstract BACKGROUND AND IMPORTANCE Temporal lobe encephaloceles are increasingly recognized as a potential cause of medically refractory epilepsy and surgical treatment has proven effective. Resection of the encephalocele and associated cortex is often sufficient to provide seizure control. However, it is difficult to determine the extent of adjacent temporal lobe that should be resected. We present a case report and our technique of a tailored inferior temporal pole resection. CLINICAL PRESENTATION A 32-yr-old man with an 11-yr history of medically refractory epilepsy. Prolonged electroencephalography (EEG) revealed frequent left and rare right frontotemporal sharp waves. Numerous seizures were captured with EEG, all of which originated from the left temporal region. Statistical parametric mapping (SPM) subtraction ictal–interictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) demonstrated ictal hyperperfusion in the anterior left temporal lobe. MRI showed 2 encephaloceles in the left anterior temporal lobe with the accompanying bony defects in the floor of the middle cranial fossa apparent on the computed tomography scan. The patient underwent left temporal craniotomy with intraoperative electrocorticography, resection of the encephaloceles, and a tailored inferior temporal lobectomy (IFTL) and repair of the middle fossa defects. At 7 mo follow up he reported seizure-freedom since surgery. CONCLUSION Resection of temporal encephalocele and adjacent cortex is safe and effective procedure for select patients with medically refractory epilepsy. This video demonstrates our technique which provides a more standardized approach to the resection.

OBJECTIVEAlmost 30% of the patients with suspected temporal lobe epilepsy (TLE) have normal results on MRI. Success rates for resection of MRI-negative TLE are less favorable, ranging from 36% to 76%. Herein the authors describe the impact of intraoperative electrocorticography (ECoG) augmented by opioid activation and its effect on postoperative seizure outcome.METHODSAdult and pediatric patients with medically resistant MRI-negative TLE who underwent standardized ECoG at the time of their elective anterior temporal lobectomy (ATL) with amygdalohippocampectomy between 1990 and 2016 were included in this study. Seizure recurrence comprised the primary outcome of interest and was assessed using Kaplan-Meier and multivariable Cox regression analysis plots based on distribution of interictal epileptiform discharges (IEDs) recorded on scalp electroencephalography, baseline and opioid-induced IEDs on ECoG, and extent of resection.RESULTSOf the 1144 ATLs performed at the authors’ institution between 1990 and 2016, 127 (11.1%) patients (81 females) with MRI-negative TLE were eligible for this study. Patients with complete resection of tissue generating IED recorded on intraoperative ECoG were less likely to have seizure recurrence compared to those with incomplete resection on univariate analysis (p < 0.05). No difference was found in seizure recurrence between patients with bilateral independent IEDs and unilateral IEDs (p = 0.15), presence or absence of opioid-induced epileptiform activation (p = 0.61), or completeness of resection of tissue with opioid-induced IEDs on intraoperative ECoG (p = 0.41).CONCLUSIONSThe authors found that incomplete resection of IED-generating tissue on intraoperative ECoG was associated with an increased chance of seizure recurrence. However, they found that induction of epileptiform activity with intraoperative opioid activation did not provide useful intraoperative data predictive of improving operative results for temporal lobectomy in MRI-negative epilepsy.