Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis.

Background: Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0-2) at last follow-up. Results: A total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = <0.0001). Older age at SE (OR = 1.384[1.046-1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362-1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069-0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168-2.404], p = 0.0060) and immediate termination of SE (OR = 3.736 [1.323-10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0-2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified. Conclusion: Our findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.

Magnetic resonance-guided laser interstitial thermal therapy for drug-resistant epilepsy: A systematic review and individual participant data meta-analysis.

Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a popular minimally invasive alternative to open resective surgery for drug-resistant epilepsy (DRE). We sought to perform a systematic review and individual participant data meta-analysis to identify independent predictors of seizure outcome and complications following MRgLITT for DRE. Eleven databases were searched from January 1, 2010 to February 6, 2021 using the terms "MR-guided ablation therapy" and "epilepsy". Multivariable mixed-effects Cox and logistic regression identified predictors of time to seizure recurrence, seizure freedom, operative complications, and postoperative neurological deficits. From 8705 citations, 46 studies reporting on 450 MRgLITT DRE patients (mean age = 29.5 ± 18.1 years, 49.6% female) were included. Median postoperative seizure freedom and follow-up duration were 15.5 and 19.0 months, respectively. Overall, 240 (57.8%) of 415 patients (excluding palliative corpus callosotomy) were seizure-free at last follow-up. Generalized seizure semiology (hazard ratio [HR] = 1.78, p = .020) and nonlesional magnetic resonance imaging (MRI) findings (HR = 1.50, p = .032) independently predicted shorter time to seizure recurrence. Cerebral cavernous malformation (CCM; odds ratio [OR] = 7.97, p < .001) and mesial temporal sclerosis/atrophy (MTS/A; OR = 2.21, p = .011) were independently associated with greater odds of seizure freedom at last follow-up. Operative complications occurred in 28 (8.5%) of 330 patients and were independently associated with extratemporal ablations (OR = 5.40, p = .012) and nonlesional MRI studies (OR = 3.25, p = .017). Postoperative neurological deficits were observed in 53 (15.1%) of 352 patients and were independently predicted by hypothalamic hamartoma etiology (OR = 5.93, p = .006) and invasive electroencephalographic monitoring (OR = 4.83, p = .003). Overall, MRgLITT is particularly effective in treating patients with well-circumscribed lesional DRE, such as CCM and MTS/A, but less effective in nonlesional cases or lesional cases with a more diffuse epileptogenic network associated with generalized seizures. This study identifies independent predictors of seizure freedom and complications following MRgLITT that may help further guide patient selection.

Predictors of outcomes after surgery for medically intractable insular epilepsy: A systematic review and individual participant data meta-analysis.

Insular epilepsy (IE) is an increasingly recognized cause of drug-resistant epilepsy amenable to surgery. However, concerns of suboptimal seizure control and permanent neurological morbidity hamper widespread adoption of surgery for IE. We performed a systematic review and individual participant data meta-analysis to determine the efficacy and safety profile of surgery for IE and identify predictors of outcomes. Of 2483 unique citations, 24 retrospective studies reporting on 312 participants were eligible for inclusion. The median follow-up duration was 2.58 years (range, 0-17 years), and 206 (66.7%) patients were seizure-free at last follow-up. Younger age at surgery (≤18 years; HR = 1.70, 95% CI = 1.09-2.66, P = .022) and invasive EEG monitoring (HR = 1.97, 95% CI = 1.04-3.74, P = .039) were significantly associated with shorter time to seizure recurrence. Performing MR-guided laser ablation or radiofrequency ablation instead of open resection (OR = 2.05, 95% CI = 1.08-3.89, P = .028) was independently associated with suboptimal or poor seizure outcome (Engel II-IV) at last follow-up. Postoperative neurological complications occurred in 42.5% of patients, most commonly motor deficits (29.9%). Permanent neurological complications occurred in 7.8% of surgeries, including 5% and 1.4% rate of permanent motor deficits and dysphasia, respectively. Resection of the frontal operculum was independently associated with greater odds of motor deficits (OR = 2.75, 95% CI = 1.46-5.15, P = .002). Dominant-hemisphere resections were independently associated with dysphasia (OR = 13.09, 95% CI = 2.22-77.14, P = .005) albeit none of the observed language deficits were permanent. Surgery for IE is associated with a good efficacy/safety profile. Most patients experience seizure freedom, and neurological deficits are predominantly transient. Pediatric patients and those requiring invasive monitoring or undergoing stereotactic ablation procedures experience lower rates of seizure freedom. Transgression of the frontal operculum should be avoided if it is not deemed part of the epileptogenic zone. Well-selected candidates undergoing dominant-hemisphere resection are more likely to exhibit transient language deficits; however, the risk of permanent deficit is very low.

MCAM+ brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4+ T lymphocytes.

The trafficking of autoreactive leucocytes across the blood-brain barrier endothelium is a hallmark of multiple sclerosis pathogenesis. Although the blood-brain barrier endothelium represents one of the main CNS borders to interact with the infiltrating leucocytes, its exact contribution to neuroinflammation remains understudied. Here, we show that Mcam identifies inflammatory brain endothelial cells with pro-migratory transcriptomic signature during experimental autoimmune encephalomyelitis. In addition, MCAM was preferentially upregulated on blood-brain barrier endothelial cells in multiple sclerosis lesions in situ and at experimental autoimmune encephalomyelitis disease onset by molecular MRI. In vitro and in vivo, we demonstrate that MCAM on blood-brain barrier endothelial cells contributes to experimental autoimmune encephalomyelitis development by promoting the cellular trafficking of TH1 and TH17 lymphocytes across the blood-brain barrier. Last, we showcase ST14 as an immune ligand to brain endothelial MCAM, enriched on CD4+ T lymphocytes that cross the blood-brain barrier in vitro, in vivo and in multiple sclerosis lesions as detected by flow cytometry on rapid autopsy derived brain tissue from multiple sclerosis patients. Collectively, our findings reveal that MCAM is at the centre of a pathological pathway used by brain endothelial cells to recruit pathogenic CD4+ T lymphocyte from circulation early during neuroinflammation. The therapeutic targeting of this mechanism is a promising avenue to treat multiple sclerosis.

Acute Effects of High-Frequency Insular Stimulation on Interictal Epileptiform Discharge Rates in Patients with Refractory Epilepsy.

Rationale: Deep brain stimulation (DBS) of several sites, such as the thalamus, has been shown to reduce seizure frequency and interictal epileptiform activity in patients with refractory epilepsy. Recent findings have demonstrated that the insula is part of the 'rich club' of highly connected brain regions. This pilot study investigated short-term effects of high-frequency (HF) insular DBS on interictal epileptiform discharge (IED) rate in patients with refractory epilepsy. Methods: Six patients with drug-resistant epilepsy undergoing an intracranial electroencephalographic study received two sets of 10 min continuous 150 Hz HF-DBS of the insula. For each patient, epileptiform activity was analyzed for a total of 80 min, starting 20 min prior to stimulation set 1 (S1), and ending 20 min after stimulation set 2 (S2). All IEDs were identified and classified according to their anatomic localization by a board-certified epileptologist. The IED rate during the 20 min preceding S1 served as a baseline for comparison with IED rate during S1, S2 and post-stimulation periods. Results: HF-DBS of the anterior insula (aINS) was performed in a patient with an aINS epileptic focus (patient 1). HF-DBS of the posterior insula (pINS) was performed in two patients with a pINS epileptic focus (patients 2 and 4), in one patient with an aINS focus (patient 3), and in two non-insular patients (patients 5 and 6). The total IED (irrespective of their location) rate significantly decreased (p < 0.01) in two patients (patients 1 and 2) during the stimulation period, whereas it significantly increased (p < 0.01) in one patient (patient 6); there was no change in the other three patients. Looking at subsets of spike localization, HF-DBS of the aINS significantly reduced aINS and orbitofrontal IEDs in patient 1 (p < 0.01), while HF-DBS of the pINS had an effect on pINS IEDs (p < 0.01) in both patients with a pINS focus; there was no significant effect of HF-DBS of the insula on IEDs in temporal or other frontal regions. Conclusion: Short-term HF-DBS of the insula had heterogeneous effects on the IED rate. Further work is required to examine factors underlying these heterogeneous effects, such as stimulation frequency, location of IEDs and subregions of the insula stimulated.

CLMP Promotes Leukocyte Migration Across Brain Barriers in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), peripheral immune cells use various cell trafficking molecules to infiltrate the CNS where they cause damage.The objective of this study was to investigate the involvement of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the CNS of patients with MS. METHODS: Expression of CLMP was measured in primary cultures of human brain endothelial cells (HBECs) and human meningeal endothelial cells (HMECs), postmortem brain samples, and peripheral blood mononuclear cells (PBMCs) from patients with MS and controls by RNA sequencing, quantitative PCR, immunohistochemistry, and flow cytometry. In vitro migration assays using HBECs and HMECs were performed to evaluate the function of CLMP. RESULTS: Using bulk RNA sequencing of primary cultures of human brain and meningeal endothelial cells (ECs), we have identified CLMP as a new potential cell trafficking molecule upregulated in inflammatory conditions. We first confirmed the upregulation of CLMP at the protein level on TNFα-activated and IFNγ-activated primary cultures of human brain and meningeal ECs. In autopsy brain specimens from patients with MS, we demonstrated an overexpression of endothelial CLMP in active MS lesions when compared with normal control brain tissue. Flow cytometry of human PBMCs demonstrated an increased frequency of CLMP+ B lymphocytes and monocytes in patients with MS, when compared with that in healthy controls. The use of a blocking antibody against CLMP reduced the migration of immune cells across the human brain and meningeal ECs in vitro. Finally, we found CLMP+ immune cell infiltrates in the perivascular area of parenchymal lesions and in the meninges of patients with MS. DISCUSSION: Collectively, our data demonstrate that CLMP is an adhesion molecule used by immune cells to access the CNS during neuroinflammatory disorders such as MS. CLMP could represent a target for a new treatment of neuroinflammatory conditions.

Déjà-vu evoked by electrical stimulation of the insula.

OBJECTIVE: Déjà-vu is a mental phenomenon commonly experienced during temporal lobe seizures and can be evoked by electrical stimulation of the temporal lobe. We analyzed reproducible déjà-vu experiences evoked by stimulating the insula in two patients with pharmacoresistant temporal lobe epilepsy. METHODS: We reviewed video-electroencephalography (EEG) recordings from extraoperative electrical cortical stimulation sessions. In addition, we performed the directed transfer function (DTF) effective connectivity measure of monopolar signals in Patient 1. To highlight elective changes due to each stimulation, we subtracted pre-stimulation DTF matrices from early poststimulation matrices. This analysis was performed for both non-inducing-déjàvu stimulation (control matrix) and déjà-vu-inducing stimulation (active matrix). Finally, the control matrix was subtracted from the active matrix. RESULTS: Comparison of effective connectivity during control stimulation versus déjà-vu-inducing stimulation revealed a reversal of connectivity levels in three main regions: the contralateral inferior insula (the ipsilateral insula could not be analyzed), bilateral mesiotemporal regions and the ipsilateral superior frontal gyrus. The drivers of evoked déjà-vu were the mesiotemporal regions (mainly ipsilateral) and the ipsilateral superior frontal gyrus. SIGNIFICANCE: Although our findings are possibly anecdotal, the insula may (in rare instances) remotely generate unexpected déjà-vu. If confirmed by further studies, this might change the assessment strategy for possible causes of anterior temporal lobectomy failure.

Insular Involvement in Cases of Epilepsy Surgery Failure.

BACKGROUND: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. METHODS: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary care centers (2004-2020). Included patients were adults who had undergone epilepsy surgeries with recurrence of seizures post-operatively and who were subsequently determined to have an insular epileptogenic focus. Clinical, electrophysiological, neuroimaging, and surgical data were synthesized. RESULTS: We present 14 patients who demonstrated insular epileptic activity post-surgery-failure as detected by intracranial EEG, MEG, or seizure improvement after insular resection. Seven patients had manifestations evoking possible insular involvement prior to their first surgery. Most patients (8/14) had initial surgeries targeting the temporal lobe. Seizure recurrence ranged from the immediate post-operative period to one year. The main modality used to determine insular involvement was MEG (8/14). Nine patients underwent re-operations that included insular resection; seven achieved a favorable post-operative outcome (Engel I or II). CONCLUSIONS: Our series suggests that lowering the threshold for suspecting insular epilepsy may be necessary to improve epilepsy surgery outcomes. Detecting insular epilepsy post-surgery-failure may allow for re-operations which may lead to good outcomes.

DICAM promotes TH17 lymphocyte trafficking across the blood-brain barrier during autoimmune neuroinflammation.

The migration of circulating leukocytes into the central nervous system (CNS) is a key driver of multiple sclerosis (MS) pathogenesis. The monoclonal antibody natalizumab proved that pharmaceutically obstructing this process is an effective therapeutic approach for treating relapsing-remitting MS (RRMS). Unfortunately, the clinical efficacy of natalizumab is somewhat offset by its incapacity to control the progressive forms of MS (PMS) and by life-threatening side effects in RRMS rising from the expression of its molecular target, very late antigen 4 (VLA4), on most immune cells and consequent impairment of CNS immunosurveillance. Here, we identified dual immunoglobulin domain containing cell adhesion molecule (DICAM) as a cell trafficking molecule preferentially expressed by T helper 17 (TH17)­polarized CD4+ T lymphocytes. We found that DICAM expression on circulating CD4+ T cells was increased in patients with active RRMS and PMS disease courses, and expression of DICAM ligands was increased on the blood-brain barrier endothelium upon inflammation and in MS lesions. Last, we demonstrated that pharmaceutically neutralizing DICAM reduced murine and human TH17 cell trafficking across the blood-brain barrier in vitro and in vivo, and alleviated disease symptoms in four distinct murine autoimmune encephalomyelitis models, including relapsing-remitting and progressive disease models. Collectively, our data highlight DICAM as a candidate therapeutic target to impede the migration of disease-inducing leukocytes into the CNS in both RRMS and PMS and suggest that blocking DICAM with a monoclonal antibody may be a promising therapeutic approach.

Déjà-vu evoked by electrical stimulation of the insula: Stimulation-induced insular déjà-vu.

OBJECTIVE: Déjà-vu is a mental phenomenon commonly experienced during temporal lobe seizures and can be evoked by electrical stimulation of the temporal lobe. We analyzed reproducible déjà-vu experiences evoked by stimulating the insula in two patients with pharmacoresistant temporal lobe epilepsy. METHODS: We reviewed video-electroencephalography (EEG) recordings from extraoperative electrical cortical stimulation sessions. In addition, we performed the directed transfer function (DTF) effective connectivity measure of monopolar signals in Patient 1. To highlight elective changes due to each stimulation, we subtracted pre-stimulation DTF matrices from early poststimulation matrices. This analysis was performed for both non-inducing-déjàvu stimulation (control matrix) and déjà-vu-inducing stimulation (active matrix). Finally, the control matrix was subtracted from the active matrix. RESULTS: Comparison of effective connectivity during control stimulation versus déjà-vu-inducing stimulation revealed a reversal of connectivity levels in three main regions: the contralateral inferior insula (the ipsilateral insula could not be analyzed), bilateral mesiotemporal regions and the ipsilateral superior frontal gyrus. The drivers of evoked déjà-vu were the mesiotemporal regions (mainly ipsilateral) and the ipsilateral superior frontal gyrus. SIGNIFICANCE: Although our findings are possibly anecdotal, the insula may (in rare instances) remotely generate unexpected déjà-vu. If confirmed by further studies, this might change the assessment strategy for possible causes of anterior temporal lobectomy failure.

Superparamagnetic iron oxide nanoparticles-based detection of neuronal activity.

Precise detection of brain regions harboring heightened electrical activity plays a central role in the understanding and treatment of diseases such as epilepsy. Superparamagnetic iron oxide nanoparticles (SPIONs) react to magnetic fields by aggregating and represent interesting candidates as new sensors for neuronal magnetic activity. We hypothesized that SPIONs in aqueous solution close to active brain tissue would aggregate proportionally to neuronal activity. We tested this hypothesis using an in vitro model of rat brain slice with different levels of activity. Aggregation was assessed with dynamic light scattering (DLS) and magnetic resonance imaging (MRI). We found that increasing brain slice activity was associated with higher levels of aggregation as measured by DLS and MRI, suggesting that the magnetic fields from neuronal tissue could induce aggregation in nearby SPIONs in solution. MRI signal change induced by SPIONs aggregation could serve as a powerful new tool for detection of brain electrical activity.

Multispectral intraoperative imaging for the detection of the hemodynamic response to interictal epileptiform discharges.

Interictal epileptiform discharges (IEDs) are brief neuronal discharges occurring between seizures in patients with epilepsy. The characterization of the hemodynamic response function (HRF) specific to IEDs could increase the accuracy of other functional imaging techniques to localize epileptiform activity, including functional near-infrared spectroscopy and functional magnetic resonance imaging. This study evaluated the possibility of using an intraoperative multispectral imaging system combined with electrocorticography (ECoG) to measure the average HRF associated with IEDs in eight patients. Inter-patient variability of the HRF is illustrated in terms of oxygenated hemoglobin peak latency, oxygenated hemoglobin increase/decrease following IEDs, and signal-to-noise ratio. A sub-region was identified using an unsupervised clustering algorithm in three patients that corresponded to the most active area identified by ECoG.

Safety of an operculoinsulectomy in the language-dominant hemisphere for refractory epilepsy.

BACKGROUND: Operculoinsular cortectomy is increasingly recognized as a therapeutic avenue for perisylvian refractory epilepsy. However, most neurosurgeons are reluctant to perform this type of procedure because of feared neurological complications, especially in the language-dominant hemisphere, as the insula is involved in speech and language processes. The goal of this retrospective study is to quantify the incidence and types of speech and language deficits associated with operculoinsulectomies in the dominant hemisphere for language, and to identify factors associated with these complications. METHODS: Clinical, imaging, and surgical data of all patients who had an operculoinsulectomy for refractory epilepsy at our center between 1998 and 2018 were reviewed. Language lateralization was determined by functional magnetic resonance imaging (fMRI) and/or Wada test. Speech and language assessments were carried out by neurosurgeons, neurologists, neuropsychologists and/or speech language pathologists, before surgery, during the first week after surgery, and at least 6 months after surgery. RESULTS: Amongst 44 operculoinsulectomies, 13 were performed in the language-dominant hemisphere. 46% of these patients presented with transient aphasia post-surgery. However, a few months later, the patients' performances on language assessments were not statistically different from before surgery, thus suggesting a complete recovery of speech and language functions. CONCLUSION: Temporary aphasias after operculoinsulectomy for refractory epilepsy in the language-dominant hemisphere are frequent, but eventually subside. Potential mechanisms underlying this recovery are discussed.

Heart Rate Variability in Insulo-Opercular Epilepsy.

BACKGROUND: We aimed to evaluate heart rate variability (HRV) changes in insulo-opercular epilepsy (IOE) and after insulo-opercular surgery. METHODS: We analyzed 5-min resting HRV of IOE patients before and after surgery. Patients' SUDEP-7 risk inventory scores were also calculated. Results were compared with age- and sex-matched patients with temporal lobe epilepsy (TLE) and healthy individuals. RESULTS: There were no differences in HRV measurements between IOE, TLE, and healthy control groups (and within each IOE group and TLE group) in preoperative and postoperative periods. In IOE patients, the SUDEP-7 score was positively correlated with pNN50 (percentage of successive RR intervals that differ by more than 50 ms) (p = 0.008) and RMSSD (root mean square of successive RR interval differences) (p = 0.019). We stratified IOE patients into those whose preoperative RMSSD values were below (Group 1a = 7) versus above (Group 1b = 9) a cut-off threshold of 31 ms (median value of a healthy population from a previous study). In group 1a, all HRV values significantly increased after surgery. In group 1b, time-domain parameters significantly decreased postoperatively. CONCLUSIONS: Our results suggest that in IOE, HRV may be either decreased in parasympathetic tone or increased globally in both sympathetic and parasympathetic tones. We found no evidence that insulo-opercular surgeries lead to major autonomic dysfunction when a good seizure outcome is reached. The increase in parasympathetic tone observed preoperatively may be of clinical concern, as it was positively correlated with the SUDEP-7 score.

Structural Connectivity Alterations in Operculo-Insular Epilepsy.

Operculo-insular epilepsy (OIE) is an under-recognized condition that can mimic temporal and extratemporal epilepsies. Previous studies have revealed structural connectivity changes in the epileptic network of focal epilepsy. However, most reports use the debated streamline-count to quantify 'connectivity strength' and rely on standard tracking algorithms. We propose a sophisticated cutting-edge method that is robust to crossing fibers, optimizes cortical coverage, and assigns an accurate microstructure-reflecting quantitative conectivity marker, namely the COMMIT (Convex Optimization Modeling for Microstructure Informed Tractography)-weight. Using our pipeline, we report the connectivity alterations in OIE. COMMIT-weighted matrices were created in all participants (nine patients with OIE, eight patients with temporal lobe epilepsy (TLE), and 22 healthy controls (HC)). In the OIE group, widespread increases in 'connectivity strength' were observed bilaterally. In OIE patients, 'hyperconnections' were observed between the insula and the pregenual cingulate gyrus (OIE group vs. HC group) and between insular subregions (OIE vs. TLE). Graph theoretic analyses revealed higher connectivity within insular subregions of OIE patients (OIE vs. TLE). We reveal, for the first time, the structural connectivity distribution in OIE. The observed pattern of connectivity in OIE likely reflects a diffuse epileptic network incorporating insular-connected regions and may represent a structural signature and diagnostic biomarker.

Deep Brain Stimulation of the Posterior Insula in Chronic Pain: A Theoretical Framework.

INTRODUCTION: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. METHODS: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. RESULTS: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. CONCLUSION: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.

Decreased self-reported appetite following insular cortex resection in patients with epilepsy.

Entrenched deep within the Sylvian fissure, the insula has long been considered one of the least understood regions of the human brain, in part due to its restricted accessibility. However, recent evidence suggests that the insula plays a key role in gustation, interoception, cognitive and emotional processes, and likely integrates these different functions to contribute to the homeostatic control of food intake. In the past decade, our team has identified the insula as a potential site of epileptogenicity, which can be successfully treated by microsurgical resection. While most surgeries are successful in controlling insular epileptic seizures and lead to few postoperative deficits, the subtle changes that may occur in food-related experiences are still unknown. Using a self-report questionnaire, the present study sought to fill this gap by assessing changes in appetite in patients who underwent unilateral partial or complete insular resections (n = 17) as part of their epilepsy surgery. We compared them to a group of patients who underwent temporal lobe epilepsy surgery (n = 22) as a lesion-control group. A majority (59%) of the insular patients reported an alteration in appetite, with most of these changes being characterized by a persistent reduction. Such changes were rarely reported following temporal lobectomy (14%). While they significantly differed in terms of appetite changes, both groups were similar when examining post-surgical changes in weight, diet, exercise and eating habits. Insular patients with altered appetite also showed behavioral signs of dysfunctional interoceptive and gustatory functions, corroborating the idea that these systems play a role in the regulation of feeding behaviours. This research pushes our understanding of the mechanisms underlying food intake and could lead to avenues for the treatment of eating disorders.

Psychological status after insulo-opercular resection in patients with epilepsy: Depression, anxiety, and quality of life.

Insular epilepsy is increasingly recognized in epilepsy surgery centers. Recent studies suggest that resection of an epileptogenic zone that involves the insula as a treatment for drug-resistant seizures is associated with good outcomes in terms of seizure control. However, despite the existing evidence of a role of the insula in emotions and affective information processing, the long-term psychological outcome of patients undergoing these surgeries remain poorly documented. A group of 27 adults (18 women) who underwent an insulo-opercular resection (in combination with a part of the temporal lobe in 10, and of the frontal lobe in 5) as part of epilepsy surgery at our center between 2004 and 2019 completed psychometric questionnaires to assess depression (Beck Depression Inventory - 2nd edition; BDI-II), anxiety (State-Trait Anxiety Inventory, Trait Version; STAI-T), and quality of life (Patient Weighted Quality of Life In Epilepsy; QOLIE-10-P). Scores were compared to those of patients who had standard temporal lobe epilepsy (TLE) surgery with similar socio-demographic and disease characteristics. Seizure control after insular epilepsy surgery was comparable to that observed after TLE surgery, with a majority of patients reporting being seizure free (insular: 63.0%; temporal: 63.2%) or having rare disabling seizures (insular: 7.4%; temporal: 18.4%) at the time of questionnaire completion. Statistical comparisons revealed no significant group difference on scores of depression, anxiety, or quality of life. Hemisphere or extent of insular resection had no significant effect on the studied variables. In the total sample, employment status and seizure control, but not location of surgery, significantly predicted quality of life. Self-reported long-term psychological status after insulo-opercular resection as part of epilepsy surgery thus appears to be similar to that observed after TLE surgery, which is commonly performed in epilepsy surgery centers.

Feasibility of implantable iron oxide nanoparticles in detecting brain activity-proof of concept in a rat model.

BACKGROUND: Precise detection of zones of increased brain activity is a crucial aspect in the delineation of the cortical region responsible for epilepsy (epileptic focus). When possible, removal of this area can lead to improved control of epilepsy or even its cure. This study explores a new method of detection of electrical brain activity based on the surgical implantation of iron oxide superparamagnetic nanoparticles (SPIONs). By their magnetic nature, SPIONs tend to aggregate in the presence of magnetic fields. This study aims to demonstrate if brain's magnetic fields could change the aggregation status of SPIONs in a rat model. METHODS: Plastic containers (capsules) containing SPIONs in aqueous suspension were implanted over the cortex of either rats rendered epileptic or naive rats (sham). A model of focal epilepsy using cortical penicillin injection was used for the epileptic rats. Capsules not implanted in rats served as control. Using magnetic resonance imaging (MRI), the aggregation status of SPIONs contained in the capsules was assessed via measurement of the T2 relaxivity time of the solutions. RESULTS: Eight Rats were used for the experiments, with 4 rats in each group (epileptic and sham). One Rat in the sham group died immediately after surgery and 3 rats failed to demonstrate the expected behavior after intervention (2 rats in epileptic group with limited observable seizures and 1 rat in the sham group having repeated seizures). T2 of the control capsules were significantly lower than those implanted in rats (146 ms vs 7.6 ms, p < 0.001), suggesting a higher degree of SPIONs aggregation in the implanted capsules. No significant difference in T2 could be demonstrated between epileptic and sham rats. CONCLUSIONS: SPIONs implanted over the cortex of active brain showed an increased aggregation status, confirming their potential as a new marker for brain activity. One of the main advantages of SPIONs is that their aggregation status can be measured at a distance with MRI, taking advantage of its high spatial resolution and imaging capacities. The current model was suboptimal to confirm if epileptic activity can be differentiated from normal brain activity using SPIONs.

Facial palsy after temporal lobectomy for epilepsy: illustrative cases.

BACKGROUND: Facial palsy is a rare, unexpected complication of temporal lobectomy (TL) for intractable epilepsy. Even without direct manipulation, the facial nerve fibers may be at risk of injury during supratentorial surgery, including TL. OBSERVATIONS: The authors presented two cases of facial palsy after unremarkable TL. In the first case, the palsy appeared in a delayed fashion and completely resolved within weeks. In the second case, facial nerve dysfunction was observed immediately after surgery, followed by progressive recovery over 2 years. The second patient had a dehiscence of the roof of the petrous bone overlying the geniculate ganglion, which put the facial nerve at risk of bipolar coagulation thermal injury. LESSONS: Two major mechanisms could explain the loss of facial nerve function after TL: surgery-related indirect inflammation of the nerve resulting in herpesvirus reactivation and delayed dysfunction (Bell's palsy) or indirect thermal damage to the geniculate ganglion through a dehiscent petrous roof.