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.

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.

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.

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.

Sensory profile alterations in patients with insular epilepsy surgery: Preliminary findings.

The insular cortex is now well-established as a potential site of epileptogenesis in patients with drug-resistant epilepsy, and its resection has been associated with good outcomes in terms of seizure control. However, given the role of the insula in sensory processing and in visceral information integration, it remains unclear whether insular cortex epilepsy and its surgery are associated with disturbances in sensory information processing and visceral sensation processes as experienced in daily life. In the present study, we examined such sensory disturbances in a group of patients (n = 17) who underwent epilepsy surgery involving a resection of the insula and compared them to a lesion-control group of patients with temporal epilepsy surgery (n = 22) and a healthy control group (n = 29) matched for age, gender, and education. Participants were assessed on the self-report "Adolescent/Adult Sensory Profile" questionnaire at least four months after surgery. Our series of one-way analyses of variance (ANOVAs) revealed that insular and temporal resections in patients with drug-refractory epilepsy were associated with a low "sensation seeking" behavior reflecting a lack of engagement with sensory inputs from the environment. Furthermore, insular resections were associated with impairments in the "active behavioral responses" for the gustatory/olfactory modalities. These preliminary findings suggest that insular resections may be associated with mild to moderate alterations in sensory processing.

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.

Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system.

Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4+ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.

The effects of insular and mesiotemporal lesions on affective information processing: Preliminary evidence from patients with epilepsy surgery.

Depressive symptoms and anxiety are common complaints in patients who have had epilepsy surgery. Recent studies have reported disturbances in emotional memory, facial and vocal emotion recognition, and affective learning after temporal lobe and/or insular resection for drug-resistant seizures, suggesting that these regions may be involved in emotional processes underlying psychological symptoms. The insula is a core component of the salience network and is thought to be involved in processing emotions such as disgust, and the role of mesial temporal lobe structures in affective processing is well established. However, to our knowledge, no study has yet investigated whether attentional processing of affective information is altered when these structures are resected as part of an epilepsy surgery. The present study examined the interference control capacity and attentional biases for emotional information in adult patients with epilepsy who underwent temporal lobe resections including the amygdala and hippocampus (n = 15) and/or partial or complete insular resections (n = 16). Patients were tested on an Emotional Stroop test and on a Dot-Probe task using fearful and disgusting pictures and were compared with a healthy control group (n = 30) matched for age, gender, and education. Repeated-measures analyses of variances revealed a significant effect of emotional words on color naming speed in the Emotional Stroop task among insular patients, which was not observed in the other groups. By contrast, the groups did not differ on Dot-Probe task performance. These preliminary findings suggest that insular damage may alter emotional interference control.

Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy.

PURPOSE: Our purpose was to determine the role of CHRNA4 and CHRNB2 in insular epilepsy. METHOD: We identified two patients with drug-resistant predominantly sleep-related hypermotor seizures, one harboring a heterozygous missense variant (c.77C>T; p. Thr26Met) in the CHRNB2 gene and the other a heterozygous missense variant (c.1079G>A; p. Arg360Gln) in the CHRNA4 gene. The patients underwent electrophysiological and neuroimaging studies, and we performed functional characterization of the p. Thr26Met (c.77C>T) in the CHRNB2 gene. RESULTS: We localized the epileptic foci to the left insula in the first case (now seizure-free following epilepsy surgery) and to both insulae in the second case. Based on tools predicting the possible impact of amino acid substitutions on the structure and function of proteins (sorting intolerant from tolerant and PolyPhen-2), variants identified in this report could be deleterious. Functional expression in human cell lines of α4ß2 (wild-type), α4ß2-Thr26Met (homozygote), and α4ß2/ß2-Thr26Met (heterozygote) nicotinic acetylcholine receptors revealed that the mutant subunit led to significantly higher whole-cell nicotinic currents. This feature was observed in both homo- and heterozygous conditions and was not accompanied by major alterations of the current reversal potential or the shape of the concentration-response relation. CONCLUSIONS: This study suggests that variants in CHRNB2 and CHRNA4, initially linked to autosomal dominant nocturnal frontal lobe epilepsy, are also found in patients with predominantly sleep-related insular epilepsy. Although the reported variants should be considered of unknown clinical significance for the moment, identification of additional similar cases and further functional studies could eventually strengthen this association.

Utility of magnetic source imaging in nonlesional focal epilepsy: a prospective study.

OBJECTIVE: For patients with nonlesional refractory focal epilepsy (NLRFE), localization of the epileptogenic zone may be more arduous than for other types of epilepsy and frequently requires information from multiple noninvasive presurgical modalities and intracranial EEG (icEEG). In this prospective, blinded study, the authors assessed the clinical added value of magnetic source imaging (MSI) in the presurgical evaluation of patients with NLRFE. METHODS: This study prospectively included 57 consecutive patients with NLRFE who were considered for epilepsy surgery. All patients underwent noninvasive presurgical evaluation and then MSI. To determine the surgical plan, discussion of the results of the presurgical evaluation was first undertaken while discussion participants were blinded to the MSI results. MSI results were then presented. MSI influence on the initial management plan was assessed. RESULTS: MSI results influenced patient management in 32 patients. MSI results led to the following changes in surgical strategy in 14 patients (25%): allowing direct surgery in 6 patients through facilitating the detection of subtle cortical dysplasia in 4 patients and providing additional concordant diagnostic information to other presurgical workup in another 2 patients; rejection of surgery in 3 patients originally deemed surgical candidates; change of plan from direct surgery to icEEG in 2 patients; and allowing icEEG in 3 patients deemed not surgical candidates. MSI results led to changed electrode locations and contact numbers in another 18 patients. Epilepsy surgery was performed in 26 patients influenced by MSI results and good surgical outcome was achieved in 21 patients. CONCLUSIONS: This prospective, blinded study showed that information provided by MSI allows more informed icEEG planning and surgical outcome in a significant percentage of patients with NLRFE and should be included in the presurgical workup in those patients.

The clinical impact of integration of magnetoencephalography in the presurgical workup for refractory nonlesional epilepsy.

OBJECTIVE: For patients with nonlesional refractory focal epilepsy (NLRFE), localization of the epileptogenic zone is more arduous, and intracranial electroencephalography (EEG) (icEEG) is frequently required. Planning for icEEG is dependent on combined data from multiple noninvasive modalities. We report the negative impact of lack of integration of magnetoencephalography (MEG) in the presurgical workup in NLRFE. METHODS: Observational MEG case series involving 31 consecutive patients with NLRFE in an academic epilepsy center. For various reasons, MEG data were not analyzed in a timely manner to be included in the decision-making process. The presumed impact of MEG was assessed retrospectively. RESULTS: Magnetoencephalography would have changed the initial management in 21/31 (68%) had MEG results been available by reducing the number of intracranial electrodes, modifying their position, allowing for direct surgery, canceling the intracranial study, or providing enough evidence to justify one. Good surgical outcome was achieved in 11 out of 17 patients who proceeded to epilepsy surgery. Nine out of eleven had MEG clusters corresponding to the resection area, and MEG findings would have allowed for direct surgery (avoiding icEEG) in 2/11. Six patients had poor outcome including three patients where MEG would have significantly changed the outcome by modifying the resection margin. Magnetoencephalography provided superior information in 3 patients where inadequate coverage precluded accurate mapping of the epileptogenic zone. CONCLUSION: In this single center retrospective study, MEG would have changed patient management, icEEG planning, and surgical outcome in a significant percentage of patients with NLRFE and should be considered in the presurgical workup in those patients.

Precuneal epilepsy: Clinical features and surgical outcome.

OBJECTIVE: The precuneus is a complex and highly connected structure located in the medial portion of the superior parietal lobule. The clinical presentation of precuneal epilepsy is poorly characterized, mostly because these patients have seldom been distinguished from those with other types of parietal lobe epilepsy. The present study aims to improve the understanding of precuneal epilepsy by detailing its clinical features and surgical outcomes. METHODS: Six previously unreported cases of drug-resistant precuneal epilepsy investigated between 2002 and 2014 were retrospectively studied. Seizure focus was confirmed by presence of a lesion, intracranial monitoring, or post-operative seizure control when applicable. RESULTS: Seizures arising from the precuneus have heterogeneous presentations, including body movement sensation, visual auras, eye movements, vestibular manifestations, and complex motor behaviors. Two patients with an anterior precuneus lesion described body movement sensations whereas two others with a posterior precuneus lesion experienced visual symptoms. Two of the five patients who underwent epilepsy surgery achieved good seizure control (Engel IA). One patient underwent gamma knife surgery with an Engel IV outcome. Surgical complications included contralateral visual field impairment, limb hypoesthesia and hemispatial neglect. One patient developed late-onset epilepsia partialis continua from a Rolandic subdural grid-related contusion. SIGNIFICANCE: In absence of a clear precuneal epileptogenic lesion, recognition of a precuneal focus is challenging. Magnetoencephalography may sometimes localize the generator but invasive EEG remains in well-selected cases necessary to identify the seizure focus. Surgical failures may be explained by the widespread connectivity of the precuneus with distant and adjacent structures. Different ictal manifestations of precuneal epilepsy in this series provide a clinical correlate to the described functional subdivisions of the precuneus.

Magnetoencephalographic signatures of insular epileptic spikes based on functional connectivity.

Failure to recognize insular cortex seizures has recently been identified as a cause of epilepsy surgeries targeting the temporal, parietal, or frontal lobe. Such failures are partly due to the fact that current noninvasive localization techniques fare poorly in recognizing insular epileptic foci. Our group recently demonstrated that magnetoencephalography (MEG) is sensitive to epileptiform spikes generated by the insula. In this study, we assessed the potential of distributed source imaging and functional connectivity analyses to distinguish insular networks underlying the generation of spikes. Nineteen patients with operculo-insular epilepsy were investigated. Each patient underwent MEG as well as T1-weighted magnetic resonance imaging (MRI) as part of their standard presurgical evaluation. Cortical sources of MEG spikes were reconstructed with the maximum entropy on the mean algorithm, and their time courses served to analyze source functional connectivity. The results indicate that the anterior and posterior subregions of the insula have specific patterns of functional connectivity mainly involving frontal and parietal regions, respectively. In addition, while their connectivity patterns are qualitatively similar during rest and during spikes, couplings within these networks are much stronger during spikes. These results show that MEG can establish functional connectivity-based signatures that could help in the diagnosis of different subtypes of insular cortex epilepsy. Hum Brain Mapp 37:3250-3261, 2016. © 2016 Wiley Periodicals, Inc.

Spatiotemporal dynamics of affective picture processing revealed by intracranial high-gamma modulations.

Our comprehension of the neural mechanisms underlying emotional information processing has largely benefited from noninvasive electrophysiological and functional neuroimaging techniques in recent years. However, the spatiotemporal dynamics of the neural events occurring during emotional processing remain imprecise due to the limited combination of spatial and temporal resolution provided by these techniques. This study examines the modulations of high-frequency activity of intracranial electroencephalography recordings associated with affective picture valence, in epileptic patients awaiting neurosurgery. Recordings were obtained from subdural grids and depth electrodes in eight patients while they viewed a series of unpleasant, pleasant and neutral pictures from the International Affective Picture System. Broadband high-gamma (70-150 Hz) power was computed for separate 100-ms time windows and compared according to ratings of emotional valence. Compared to emotionally neutral or pleasant pictures, unpleasant stimuli were associated with an early and long-lasting (≈200-1,000 ms) bilateral increase in high-gamma activity in visual areas of the occipital and temporal lobes, together with a late and transient (≈500-800 ms) decrease found bilaterally in the lateral prefrontal cortex (PFC). Pleasant pictures were associated with increased gamma activity in the occipital cortex, compared to the emotionally neutral stimuli. Consistent with previous studies, our results provide direct evidence of emotion-related modulations in the visual ventral pathway during picture processing. Results in the lateral PFC also shed light on the neural mechanisms underlying its role in negative emotions processing. This study demonstrates the utility of intracranial high-gamma modulations to study emotional process with a high spatiotemporal precision.

Different effects of anterior temporal lobectomy and selective amygdalohippocampectomy on verbal memory performance of patients with epilepsy.

The advantage of selective amygdalohippocampectomy (SAH) over anterior temporal lobectomy (ATL) for the treatment of temporal lobe epilepsy (TLE) remains controversial. Because ATL is more extensive and involves the lateral and medial parts of the temporal lobe, it may be predicted that its impact on memory is more important than SAH, which involves resection of medial temporal structures only. However, several studies do not support this assumption. Possible explanations include task-specific factors such as the extent of semantic and syntactic information to be memorized and failure to control for main confounders. We compared preoperative vs. postoperative memory performance in 13 patients with SAH with 26 patients who underwent ATL matched on side of surgery, IQ, age at seizure onset, and age at surgery. Memory function was assessed using the Logical Memory subtest from the Wechsler Memory Scales - 3rd edition (LM-WMS), the Rey Auditory Verbal Learning Test (RAVLT), the Digit Span subtest from the Wechsler Adult Intelligence Scale, and the Rey-Osterrieth Complex Figure Test. Repeated measures analyses of variance revealed opposite effects of SAH and ATL on the two verbal learning memory tests. On the immediate recall trial of the LM-WMS, performance deteriorated after ATL in comparison with that after SAH. By contrast, on the delayed recognition trial of the RAVLT, performance deteriorated after SAH compared with that after ATL. However, additional analyses revealed that the latter finding was only observed when surgery was conducted in the right hemisphere. No interaction effects were found on other memory outcomes. The results are congruent with the view that tasks involving rich semantic content and syntactical structure are more sensitive to the effects of lateral temporal cortex resection as compared with mesiotemporal resection. The findings highlight the importance of task selection in the assessment of memory in patients undergoing TLE surgery.

Neuropsychological performance before and after partial or complete insulectomy in patients with epilepsy.

Resection of the insular cortex is becoming more frequent as it is increasingly recognized that a nonnegligible proportion of surgical candidates with drug-resistant epilepsy have an epileptogenic zone that involves the insula. In the last decades, however, the insula has been proposed to be involved in several neuropsychological functions, and there is a lack of documentation on whether partial or complete insulectomy results in permanent cognitive impairments in this clinical population. In this study, we conducted standard preoperative and postoperative neuropsychological assessments in 18 patients undergoing epilepsy surgery that included the removal of the insula in the right (n=13) or the left (n=5) hemisphere. Postoperative testing was conducted at least five months after surgery. Cognitive impairments were common and heterogeneous prior to surgery, with language and verbal memory impairments being especially frequent among patients in whom epileptic seizures originated from the left hemisphere. After surgery, declines and improvements occurred on a variety of outcomes, although new deficits were relatively infrequent among patients who had obtained normal performance at baseline. Statistical comparisons between preoperative and postoperative assessments revealed significant deterioration of only one outcome - the color naming condition of the Stroop test - which relies on oro-motor speed and lexical access. These findings suggest that partial or complete resection of the insular cortex in patients with drug-refractory epilepsy can be conducted without major permanent neuropsychological impairments in a vast majority of patients. However, small decrements in specific cognitive functions can be expected, which should also be taken into account when considering the surgical option in this clinical population.

Recognizing an object from the sum of its parts: an intracranial study on alpha rhythms.

Little is known about the relation of alpha rhythms and object recognition. Alpha has been generally proposed to be associated with attention and memory and to be particularly important for the mediation of long-distance communication between neuronal populations. However, how these apply to object recognition is still unclear. This study aimed at describing the spatiotemporal dynamics of alpha rhythms while recognizing fragmented images of objects presented for the first time and presented again 24 hr later. Intracranial electroencephalography was performed in six epileptic patients undergoing presurgical evaluation. Time-frequency analysis revealed a strong alpha activity, mainly of the evoked type, propagating from posterior cerebral areas to anterior regions, which was similar whether the objects were recognized or not. Phase coherence analysis, however, showed clear phase synchronization specific for the moment of recognition. Twenty-four hr later, frontal regions displayed stronger alpha activity and more distributed phase synchronization than when images were presented for the first time. In conclusion, alpha amplitude seems to be related to nonspecific mechanism. Phase coherence analysis suggests a communicational role of alpha activity in object recognition, which may be important for the comparison between bottom-up representations and memory templates.

Different localizations underlying cortical gelastic epilepsy: case series and review of literature.

BACKGROUND: Gelastic seizures (GS) are classically observed with hypothalamic hamartomas but they can also be associated with cortical epileptogenic foci. OBJECTIVE: To study the different cortical localizations associated with GS. METHODS: We reviewed the data from all patients with cortical GS investigated in our epilepsy unit from 1974 to 2012 and in the literature from 1956 to 2013. RESULTS: Sixteen cases were identified in our database and 77 in the literature. Investigations provided confident focus localization in 9 and 18, respectively. In our series, the identified foci were located in the mesial temporal structures (2 left, 1 right), lateral temporal cortex (1 right), superior frontal gyrus (1 left), and operculoinsular region [3 right (orbitofrontal or frontal operculum extending into the anterior insula) and 1 left (frontal operculum extending into the anterior insula)]. In the literature, the identified foci (13 right/5 left) were located in the temporal lobe of 4 (1 right inferior, 1 right medial and inferior, 1 right posterior middle, inferior extending posteriorly to the lingual gyrus, and 1 left middle, inferior, and medial), in the frontal lobe of 12 [10 (6 right/4 left) medial (i.e., superior, medial frontal, and/or anterior cingulate gyri), 1 lateral (right anterior inferior frontal gyrus), and 1 right medioposterior orbitofrontal cortex] and in the parietal lobe of 2 (1 left superior parietal lobule and 1 right parietal operculum) patients. CONCLUSION: Ictal laughter is a poorly lateralizing and localizing feature as it may be encountered in patients with a focus in the left or right frontal, temporal, parietal, or insular lobe.

Prognostic tests and antiepileptic drug withdrawal after epilepsy surgery.

Approximately one in three patients with a successful epilepsy surgery will have seizure recurrence following antiepileptic drugs (AED) withdrawal. The value of postoperative testing for predicting seizure relapse after AED tapering is not clear. The purpose of this study was to review the literature for evidence on the use of postoperative investigations before AED discontinuation after successful epilepsy surgery. We were unable to identify studies on the prognostic value of postoperative magnetic resonance imaging and AED blood levels. The literature review yielded seven studies on the predictive value of electroencephalography. Four studies found no association between interictal discharges (IED) and seizure relapse. These studies suffered from various limitations due to their retrospective design and generally small cohorts. Two of the three studies reporting a positive association were prospective and provided strong evidence of an increased risk of seizure recurrence with presence of postoperative IED in successfully operated patients undergoing AED withdrawal.

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.