Vagus nerve stimulation does not alter brainstem nuclei morphology in patients with refractory epilepsy.

OBJECTIVE: To describe morphological characteristics of the brainstem nuclei in response to chronic vagus nerve stimulation (VNS) in patients with refractory epilepsy. BACKGROUND: VNS is a treatment option for individuals with medically refractory epilepsy. While treatment with VNS may achieve up to 50% seizure reduction and is protective against sudden unexpected death in epilepsy (SUDEP), its mechanism of action is not fully understood. Long-term structural and cellular changes in response to VNS have rarely been addressed in humans. METHODS: Four autopsy cases with history of chronic epilepsy treated with VNS (VNS+) and 4 age- and sex-matched chronic epilepsy-related death cases without VNS (VNS-) were included. Detailed clinical and postmortem data were obtained. Serial horizontal sections of the brainstem were prepared and stained with hematoxylin, eosin, and luxol fast blue (HE/LFB). Three regions of interest (ROIs) were delineated, including nucleus tractus solitarius (NTS), locus coeruleus (LC), and the rostral pontine group of raphe nuclei (rRN). Immunohistochemistry studies were performed using antibodies to GFAP, NeuN, HLA-DR, and IBA-1. Immunolabeling index was analyzed. RESULTS: Three of the 4 VNS+ patients and all 4 control (VNS-) patients died of SUDEP. There was no laterality difference in the NeuN, GFAP, HLA-DR and IBA-1 expression in LC and NTS of VNS+ patients. Similarly, there was no difference in the rRN, LC, and NTS between the VNS+ and VNS- groups. CONCLUSION: This study represents the first histopathological study of the long-term effects of VNS therapy in the human brain. There was no difference observed in the neuronal cell number, degree of astrocytosis, and neuroinflammation in the main brainstem vagal afferent nuclei after prolonged VNS treatment in patients with refractory epilepsy.

Direct visualization and characterization of the human zona incerta and surrounding structures.

The zona incerta (ZI) is a small gray matter region of the deep brain first identified in the 19th century, yet direct in vivo visualization and characterization has remained elusive. Noninvasive detection of the ZI and surrounding region could be critical to further our understanding of this widely connected but poorly understood deep brain region and could contribute to the development and optimization of neuromodulatory therapies. We demonstrate that high resolution (submillimetric) longitudinal (T1) relaxometry measurements at high magnetic field strength (7 T) can be used to delineate the ZI from surrounding white matter structures, specifically the fasciculus cerebellothalamicus, fields of Forel (fasciculus lenticularis, fasciculus thalamicus, and field H), and medial lemniscus. Using this approach, we successfully derived in vivo estimates of the size, shape, location, and tissue characteristics of substructures in the ZI region, confirming observations only previously possible through histological evaluation that this region is not just a space between structures but contains distinct morphological entities that should be considered separately. Our findings pave the way for increasingly detailed in vivo study and provide a structural foundation for precise functional and neuromodulatory investigation.

Seizure Freedom in Temporal Plus Epilepsy Surgery Following Stereo-Electroencephalography.

BACKGROUND: "Temporal plus" epilepsy (TPE) is a term that is used when the epileptogenic zone (EZ) extends beyond the boundaries of the temporal lobe. Stereotactic electroencephalography (SEEG) has been essential to identify additional EZs in adjacent structures that might be part of the temporal lobe/limbic network. OBJECTIVE: We present a small case series of temporal plus cases successfully identified by SEEG who were seizure-free after resective surgery. METHODS: We conducted a retrospective analysis of 156 patients who underwent SEEG in 5 years. Six cases had TPE and underwent anterior temporal lobectomy (ATL) with additional extra-temporal resections. RESULTS: Five cases had a focus on the right hemisphere and one on the left. Three cases were non-lesional and three were lesional. Mean follow-up time since surgery was 2.9 years (SD ± 1.8). Three patients had subdural electrodes investigation prior or in addition to SEEG. All patients underwent standard ATL and additional extra-temporal resections during the same procedure or at a later date. All patients were seizure-free at their last follow-up appointment (Engel Ia = 3; Engel Ib = 2; Engel Ic = 1). Pathology was nonspecific/gliosis for all six cases. CONCLUSION: TPE might explain some of the failures in temporal lobe epilepsy surgery. We present a small case series of six patients in whom SEEG successfully identified this phenomenon and surgery proved effective.

Paresthesia-Free Spinal Nerve Root Stimulation for the Treatment of Chronic Neuropathic Pain.

OBJECTIVE: Stimulation of the dorsal spinal roots, or spinal nerve root stimulation (SNRS), is a neuromodulation modality that can target pain within specific dermatomal distributions. The use of paresthesia-free stimulation has been described with conventional dorsal column spinal cord stimulation, although has yet to be described for SNRS. This objective of this study was to investigate the efficacy of paresthesia-free high-frequency (1000-1200 Hz) SNRS in the treatment of intractable, dermatomal neuropathic pain. MATERIALS AND METHODS: A retrospective chart review was performed on 14 patients implanted with SNRS in varying distributions: Ten patients initially received tonic stimulation and crossed over to a paresthesia-free paradigm and four patients received only paresthesia-free stimulation. The primary outcome was reduction in pain severity (visual analog scale [VAS]), measured at baseline and follow-up to 24 months with paresthesia-free stimulation. RESULTS: All 14 patients who received paresthesia-free stimulation had significant improvement in pain severity at a mean follow-up of 1.39 ± 0.15 years (VAS 7.46 at baseline vs. 3.25 at most recent follow-up, p < 0.001). Ten patients were initially treated with tonic stimulation and crossed over to paresthesia-free stimulation after a mean of 61.7 months. Baseline pain in these crossover patients was significantly improved at last follow-up with tonic stimulation (VAS 7.65 at baseline vs. 2.83 at 48 months, p < 0.001), although all patients developed uncomfortable paresthesias. There was no significant difference in pain severity between patients receiving tonic and paresthesia-free stimulation. CONCLUSIONS: We present real-world outcomes of patients with intractable dermatomal neuropathic pain treated with paresthesia-free, high-frequency SNRS. We demonstrate its effectiveness in providing pain reduction at a level comparable to tonic SNRS up to 24 months follow-up, without producing uncomfortable paresthesias.

An assessment of KIR channel function in human cerebral arteries.

In the rodent cerebral circulation, inward rectifying K+ (KIR) channels set resting tone and the distance over which electrical phenomena spread along the arterial wall. The present study sought to translate these observations into human cerebral arteries obtained from resected brain tissue. Computational modeling and a conduction assay first defined the impact of KIR channels on electrical communication; patch-clamp electrophysiology, quantitative PCR, and immunohistochemistry then characterized KIR2.x channel expression/activity. In keeping with rodent observations, computer modeling highlighted that KIR blockade should constrict cerebral arteries and attenuate electrical communication if functionally expressed. Surprisingly, Ba2+ (a KIR channel inhibitor) had no effect on human cerebral arterial tone or intercellular conduction. In alignment with these observations, immunohistochemistry and patch-clamp electrophysiology revealed minimal KIR channel expression/activity in both smooth muscle and endothelial cells. This absence may be reflective of chronic stress as dysphormic neurons, leukocyte infiltrate, and glial fibrillary acidic protein expression was notable in the epileptic cortex. In closing, KIR2.x channel expression is limited in human cerebral arteries from patients with epilepsy and thus has little impact on resting tone or the spread of vasomotor responses. NEW & NOTEWORTHY KIR2.x channels are expressed in rodent cerebral arterial smooth muscle and endothelial cells. As they are critical to setting membrane potential and the distance signals conduct, we sought to translate this work into humans. Surprisingly, KIR2.x channel activity/expression was limited in human cerebral arteries, a paucity tied to chronic brain stress in the epileptic cortex. Without substantive expression, KIR2.x channels were unable to govern arterial tone or conduction.

A framework for evaluating correspondence between brain images using anatomical fiducials.

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point-based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.

Quantification of local geometric distortion in structural magnetic resonance images: Application to ultra-high fields.

Ultra-high field magnetic resonance imaging (MRI) provides superior visualization of brain structures compared to lower fields, but images may be prone to severe geometric inhomogeneity. We propose to quantify local geometric distortion at ultra-high fields in in vivo datasets of human subjects scanned at both ultra-high field and lower fields. By using the displacement field derived from nonlinear image registration between images of the same subject, focal areas of spatial uncertainty are quantified. Through group and subject-specific analysis, we were able to identify regions systematically affected by geometric distortion at air-tissue interfaces prone to magnetic susceptibility, where the gradient coil non-linearity occurs in the occipital and suboccipital regions, as well as with distance from image isocenter. The derived displacement maps, quantified in millimeters, can be used to prospectively evaluate subject-specific local spatial uncertainty that should be taken into account in neuroimaging studies, and also for clinical applications like stereotactic neurosurgery where accuracy is critical. Validation with manual fiducial displacement demonstrated excellent correlation and agreement. Our results point to the need for site-specific calibration of geometric inhomogeneity. Our methodology provides a framework to permit prospective evaluation of the effect of MRI sequences, distortion correction techniques, and scanner hardware/software upgrades on geometric distortion.

Novel connectivity map normalization procedure for improved quantitative investigation of structural thalamic connectivity in temporal lobe epilepsy patients.

BACKGROUND: Connectivity studies targeting the thalamus have revealed patterns of atrophy and deafferentiation in temporal lobe epilepsy (TLE). The thalamus can be parcellated using probabilistic tractography to demonstrate regions of cortical connectivity; however, sensitivity to smaller or less connected regions is low. PURPOSE/HYPOTHESIS: To investigate thalamic structural connectivity in a wider range of cortical and limbic structures in TLE patients using a novel connectivity map normalization procedure. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: Patients (N = 23) with medication-resistant TLE and 34 healthy age-matched controls. FIELD STRENGTH/SEQUENCE: For T1 and diffusion weighting a spoiled gradient sequence was used (41 gradient directions [b = 1000]). For T2 mapping balanced steady-state free precession was used. Images were acquired at 3T. ASSESSMENT: Probabilistic tractography and a novel normalization procedure allowed comparison of groups with respect to thalamic connected volume, quantitative MRI, and diffusion tensor imaging (DTI) metrics. STATISTICAL TESTS: Independent samples t-test, Cohen's d, and Mann-Whitney tests. RESULTS: Following normalization, significant differences in thalamic connected volumes were found in left TLE vs. controls bilaterally within the posterior parahippocampal gyrus (L: P = 0.007, confidence interval [CI]: [173.306,1044.41], effect size [ES] = 1.072; R: P = 0.017, CI: [98.677,947.653], ES = 0.945), and contralaterally in the anterior temporal neocortex (P = 0.01, CI: (-2348.09, -333.719), ES = -1.021). This procedure revealed differences in thalamic connected volumes, where previously published procedures could not, and provided a basis for exploratory analysis of quantitative MRI and DTI metrics. DATA CONCLUSION: The novel connectivity map normalization scheme proposed here successfully allowed comparison between a wider range of cortical and limbic structures. Multiple volumetric and quantitative MRI and DTI-related differences between TLE patients and controls were revealed following normalization. With validation from a larger cohort, thalamo-temporal connection aberrancies may become useful biomarkers of disease states and probabilistic tractography as a procedure for identification of thalamic targets in modulatory therapies for TLE. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1529-1539.

Intracranial Electroencephalographic Monitoring: From Subdural to Depth Electrodes.

At the London Health Sciences Centre Epilepsy Program, stereotactically implanted depth electrodes have largely replaced subdural electrodes in the presurgical investigation of patients with drug-resistant epilepsy over the past 4 years. The rationale for this paradigm shift was more experience with, and improved surgical techniques for, stereoelectroencephalography, a possible lower-risk profile for depth electrodes, better patient tolerability, shorter operative time, as well as increased recognition of potential surgical targets that are not accessible to subdural electrodes.

Investigation of hippocampal substructures in focal temporal lobe epilepsy with and without hippocampal sclerosis at 7T.

PURPOSE: To provide a more detailed investigation of hippocampal subfields using 7T magnetic resonance imaging (MRI) for the identification of hippocampal sclerosis in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Patients (n = 13) with drug-resistant TLE previously identified by conventional imaging as having hippocampal sclerosis (HS) or not (nine without HS, four HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( R2*) were studied between the two groups. In addition, qualitative assessment at 7T and clinical outcomes were correlated with measured subfield changes. RESULTS: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 (P = 0.001) and CA4+DG (P < 0.001). Volumetry also uncovered subfield atrophy in 33% of patients without HS, which had not been detected using conventional imaging. R2* was significantly lower in the CA4+DG subfields (P = 0.001) and the whole hippocampus (P = 0.029) of HS patients compared to controls but not significantly lower than the group without HS (P = 0.077, P = 0.109). No correlation was found between quantitative volumetry and qualitative assessment as well as surgical outcomes (Sub, P = 0.495, P = 0.567, P = 0.528; CA1, P = 0.104 ± 0.171, P = 0.273, P = 0.554; CA2+CA3, P = 0.517, P = 0.952, P = 0.130 ± 0.256; CA4+DG, P = 0.052 ± 0.173, P = 0.212, P = 0.124 ± 0.204; WholeHipp, P = 0.187, P = 0.132 ± 0.197, P = 0.628). CONCLUSION: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T is capable of identifying characteristic patterns of hippocampal atrophy in HS patients; however, difficulty remains in using imaging to identify hippocampal pathologies in cases without HS. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1359-1370.

Cervical Spinal Cord and Dorsal Nerve Root Stimulation for Neuropathic Upper Limb Pain.

BACKGROUND: Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain in the lower limbs. Upper limb pain comprises a significant proportion of neuropathic pain patients, but is often difficult to target specifically and consistently with paresthesias. We hypothesized that the use of dorsal nerve root stimulation (DNRS), as an option along with SCS, would help us better relieve pain in these patients. METHODS: All 35 patients trialed with spinal stimulation for upper limb pain between July 1, 2011, and October 31, 2013, were included. We performed permanent implantation in 23/35 patients based on a visual analogue scale pain score decrease of ≥50% during trial stimulation. RESULTS: Both the SCS and DNRS groups had significant improvements in average visual analogue scale pain scores at 12 months compared with baseline, and the majority of patients in both groups obtained ≥50% pain relief. The majority of patients in both groups were able to reduce their opioid use, and on average had improvements in Short Form-36 quality of life scores. Complication rates did not differ significantly between the two groups. CONCLUSIONS: Treatment with SCS or DNRS provides meaningful long-term relief of chronic neuropathic pain in the upper limbs.

In vivo MRI signatures of hippocampal subfield pathology in intractable epilepsy.

OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo. EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG. PRINCIPAL OBSERVATIONS: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy. CONCLUSION: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology.

Magnetic resonance imaging and histology correlation in the neocortex in temporal lobe epilepsy.

OBJECTIVE: To investigate the histopathological correlates of quantitative relaxometry and diffusion tensor imaging (DTI) and to determine their efficacy in epileptogenic lesion detection for preoperative evaluation of focal epilepsy. METHODS: We correlated quantitative relaxometry and DTI with histological features of neuronal density and morphology in 55 regions of the temporal lobe neocortex, selected from 13 patients who underwent epilepsy surgery. We made use of a validated nonrigid image registration protocol to obtain accurate correspondences between in vivo magnetic resonance imaging and histology images. RESULTS: We found T1 to be a predictor of neuronal density in the neocortical gray matter (GM) using linear mixed effects models with random effects for subjects. Fractional anisotropy (FA) was a predictor of neuronal density of large-caliber neurons only (pyramidal cells, layers 3 and 5). Comparing multivariate to univariate mixed effects models with nested variables demonstrated that employing T1 and FA together provided a significantly better fit than T1 or FA alone in predicting density of large-caliber neurons. Correlations with clinical variables revealed significant positive correlations between neuronal density and age (rs = 0.726, pfwe = 0.021). This study is the first to relate in vivo T1 and FA values to the proportion of neurons in GM. INTERPRETATION: Our results suggest that quantitative T1 mapping and DTI may have a role in preoperative evaluation of focal epilepsy and can be extended to identify GM pathology in a variety of neurological disorders.

Timing of early and late seizure recurrence after temporal lobe epilepsy surgery.

PURPOSE: Seizure recurrence after epilepsy surgery has been classified as either early or late depending on the recurrence time after operation. However, time of recurrence is variable and has been arbitrarily defined in the literature. We established a mathematical model for discriminating patients with early or late seizure recurrence, and examined differences between these two groups. METHODS: A historical cohort of 247 consecutive patients treated surgically for temporal lobe epilepsy was identified. In patients who recurred, postoperative time until seizure recurrence was examined using an receiver-operating characteristic (ROC) curve to determine the best cutoff for predicting long-term prognosis, dividing patients in those with early and those with late seizure recurrence. We then compared the groups in terms of a number of clinical, electrophysiologic, and radiologic variables. KEY FINDINGS: Seizures recurred in 107 patients (48.9%). The ROC curve demonstrated that 6 months was the ideal time for predicting long-term surgical outcome with best accuracy, (area under the curve [AUC] = 0.761; sensitivity = 78.8%; specificity = 72.1%). We observed that patients with seizure recurrence during the first 6 months started having seizures at younger age (odds ratio [OR] = 6.03; 95% confidence interval [CI] = 1.06-11.01; p = 0.018), had a worse outcome (OR = 6.85; 95% CI = 2.54-18.52; p = 0.001), needed a higher number of antiepileptic medications (OR = 2.07; 95% CI = 1.16-9.34; p = 0.013), and more frequently had repeat surgery (OR = 9.59; 95% CI = 1.18-77.88; p = 0.021). Patients with late relapse more frequently had seizures associated with trigger events (OR = 9.61; 95% CI = 3.52-26.31; p < 0.01). SIGNIFICANCE: Patients with early or late recurrence of seizures have different characteristics that might reflect diversity in the epileptogenic zone and epileptogenicity itself. These disparities might help explain variable patterns of seizure recurrence after epilepsy surgery.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

OBJECTIVE: In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. METHODS: We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. RESULTS: SEEG was performed in 155 cases during this period. 11 (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs. 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. SIGNIFICANCE: We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger datasets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Involvement of the posterior cingulate gyrus in temporal lobe epilepsy: A study using stereo-EEG.

OBJECTIVE: To analyze the involvement of the posterior cingulate gyrus (PCG) during mesial temporal lobe seizures (MTLS). METHODS: We retrospectively reviewed the stereo-EEG (SEEG) recordings of patients with MTLS performed in our institution from February 2013 to December 2020. Only patients who had electrode implantation in the PCG were included. Patients with lesions that could potentially alter the seizure spread pathways were excluded. We assessed the propagation patterns of MTLS with respect to the different structures sampled. RESULTS: Nine of 97 patients who had at least one seizure originating in the mesial temporal region met the inclusion criteria. A total of 174 seizures were analyzed. The PCG was the first site of propagation in most of the cases (8/9 patients and 77.5% of seizures, and 7/8 patients and 65.6% of seizures after excluding an outlier patient). The fastest propagation times were towards the contralateral mesial temporal region and ipsilateral PCG. Seven patients underwent standard anterior temporal lobectomy and, of these, all but one were Engel 1 at last follow up. CONCLUSION: We found the PCG to be the first propagation site of MTLS in this group of patients. These results outline the relevance of the PCG in SEEG planning strategies. Further investigations are needed to corroborate whether fast propagation to the PCG predicts a good surgical outcome.

Long-term safety of spinal cord stimulation systems in a prospective, global registry of patients with chronic pain.

Aim: The availability of long-term (>2 years) safety outcomes of spinal cord stimulation (SCS) remains limited. We evaluated safety in a global SCS registry for chronic pain. Methods: Participants were prospectively enrolled globally at 79 implanting centers and followed out to 3 years after device implantation. Results: Of 1881 participants enrolled, 1289 received a permanent SCS implant (1776 completed trial). The annualized rate of device explant was 3.5% (all causes), and 1.1% due to inadequate pain relief. Total incidence of device explantation >3 years was 7.6% (n = 98). Of these, 32 subjects (2.5%) indicated inadequate pain relief as cause for removal. Implant site infection (11 events) was the most common device-related serious adverse event (<1%). Conclusion: This prospective, global, real-world study demonstrates a high-level of safety for SCS with low rate of explant/serious adverse events. Clinical Trial Registration: NCT01719055 (ClinicalTrials.gov).

A prospective controlled study on the impact of anterior temporal lobectomy on dream content.

OBJECTIVE: Changes of dream ability and content in patients with brain lesions have been addressed in only about 100 case reports. All of these reports lack data regarding prelesional baseline dream content. Therefore, it was the objective of this study to prospectively assess dream content before and after anterior temporal lobectomy. METHODS: Using the Hall and Van de Castle system, 30 dreams before and 21 dreams after anterior temporal lobectomy for drug-resistant epilepsy were analyzed. Fifty-five dreams before and 60 dreams after stereoelectroencephalography served as controls. RESULTS: After anterior temporal lobectomy, patients had significantly less physical aggression in their dreams than preoperatively (p < 0.01, Cohen's h statistic). Dream content of patients undergoing stereoelectroencephalography showed no significant changes. CONCLUSIONS: Within the default dream network, the temporal lobe may account for aggressive dream content. Impact of general anesthesia on dream content, as a possible confounder, was ruled out.

Extraoperative electrical stimulation mapping in epilepsy presurgical evaluation: a proposal and review of the literature.

BACKGROUND: Electrical stimulation mapping (ESM) is an important tool for the localization of the seizure onset zone (SOZ) in patients with medically resistant epilepsy (MRE). ESM is the gold standard for the identification of eloquent cortex in epilepsy surgery candidates. However, there is no standard protocol outlining how to perform ESM, to obtain the most useful information possible. The objective of this study, after reviewing the literature concerning ESM, is to propose a unifying technique to validate reliable data across different centers. METHODS: In this manuscript we summarize this technique from its origin to present, and review protocols used in other centers. We also describe a protocol that has been used in our institution, which utilizes depth electrodes. RESULTS: The most common type of ESM uses a "close-loop" system, bipolar and high frequency stimulation (50 Hz). We propose to use a pulse width of 300 µs, current spanning 1-6 mA in depth electrodes and 1-11 mA in subdural-grids. Stimulation time of 5 s maximum and at least 10 s break in between the stimulations. CONCLUSIONS: ESM is a useful tool for understanding eloquent cortex as well as the epilepsy network, although there is no clear consensus regarding how it should be performed.

Long-Term Experience with Occipital and Supraorbital Nerve Stimulation for the Various Headache Disorders-A Retrospective Institutional Case Series of 96 Patients.

OBJECTIVE: We have provided long-term data on clinically meaningful pain alleviation for drug-refractory headache disorders using occipital (ONS) and supraorbital nerve stimulation (SONS). METHODS: We performed a retrospective review of 96 patients with migraine, cervicogenic headache, cluster headache, neuropathic pain of the scalp, tension-type headache, and new daily persistent headache who had undergone ONS (61.5%), SONS (11.5%), or combined ONS plus SONS (27.1%) trial implantation and definitive implantation from 2007 to 2017. Changes in pain perception over time were monitored using the visual analog scale (VAS) for pain. RESULTS: The cohort consisted of 60.4% women and 39.6% men, with a mean age of 46.9 ± 11.5 years and pain duration of 14 ± 14.1 years. Of the 96 patients, 65 (67.7%) were treatment responders to a trial (≥30% amelioration in the average or maximum VAS score for pain and/or number of headache days) that had lasted 22.5 ± 8.8 days. The reduction in their average VAS score for pain was to 37% ± 24.4% of baseline compared with 99.1% ± 24.1% of baseline for those without a response (P < 0.01). Of the 56 patients who had undergone implantation and had long-term follow-up data available for ≤10 years, 32 (57.1%) reported a ≥50% reduction in their average VAS score for pain. Four patients (6.5%) had requested hardware explantation. Stage II complications included 1 infection (1.6%) and 6 electrode dislocations (9.7%). The study limitations included the retrospective nature, lack of controls receiving placebo intervention, and randomization. CONCLUSIONS: After careful patient selection according to a positive response to a trial of ONS and/or SONS, clinically meaningful long-term benefit was achieved in 57.1% of our patients with various chronic headache conditions.