Neurological Impact of Slower Rewarming during Bypass Surgery in Infants.

BACKGROUND: Hypothermia is a neuroprotective strategy during cardiopulmonary bypass. Rewarming entailing a rapid rise in cerebral metabolism might lead to secondary neurological sequelae. In this pilot study, we aimed to validate the hypothesis that a slower rewarming rate would lower the risk of cerebral hypoxia and seizures in infants. METHODS: This is a prospective, clinical, single-center study. Infants undergoing cardiac surgery in hypothermia were rewarmed either according to the standard (+1°C in < 5 minutes) or a slow (+1°C in > 5-8 minutes) rewarming strategy. We monitored electrocortical activity via amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation by near-infrared spectroscopy during and after surgery. RESULTS: Fifteen children in the standard rewarming group (age: 13 days [5-251]) were cooled down to 26.6°C (17.2-29.8) and compared with 17 children in the slow-rewarming group (age: 9 days [4-365]) with a minimal temperature of 25.7°C (20.1-31.4). All neonates in both groups (n = 19) exhibited suppressed patterns compared with 28% of the infants > 28 days (p < 0.05). During rewarming, only 26% of the children in the slow-rewarming group revealed suppressed aEEG traces (vs. 41%; p = 0.28). Cerebral oxygenation increased by a median of 3.5% in the slow-rewarming group versus 1.5% in the standard group (p = 0.9). Our slow-rewarming group revealed no aEEG evidence of any postoperative seizures (0 vs. 20%). CONCLUSION: These results might indicate that a slower rewarming rate after hypothermia causes less suppression of electrocortical activity and higher cerebral oxygenation during rewarming, which may imply a reduced risk of postoperative seizures.

Seizure Outcome After Intraoperative Electrocorticography-Tailored Epilepsy Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic method. We assessed the current evidence to use ioECoG-tailored epilepsy surgery for improving postsurgical outcome. METHODS: PubMed and Embase were searched for original studies reporting on ≥10 cases who underwent ioECoG-tailored surgery for epilepsy, with a follow-up of at least 6 months. We used a random-effects model to calculate the overall rate of patients achieving favorable seizure outcome (FSO), defined as Engel class I, ILAE class 1, or seizure-free status. Meta-regression was used to investigate potential sources of heterogeneity. We calculated the odds ratio (OR) for estimating variables on FSO:ioECoG vs non-ioECoG-tailored surgery (if included studies contained patients with non-ioECoG-tailored surgery), ioECoG-tailored epilepsy surgery in children vs adults, temporal (TL) vs extratemporal lobe (eTL), MRI-positive vs MRI-negative, and complete vs incomplete resection of tissue that generated interictal epileptiform discharges (IEDs). A Bayesian network meta-analysis was conducted for underlying pathologies. We assessed the evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Eighty-three studies (82 observational studies, 1 trial) comprising 3,631 patients with ioECoG-tailored surgery were included. The overall pooled rate of patients who attained FSO after ioECoG-tailored surgery was 74% (95% CI 71-77) with significant heterogeneity, which was predominantly attributed to pathologies and seizure outcome classifications. Twenty-two studies contained non-ioECoG-tailored surgeries. IoECoG-tailored surgeries reached a higher rate of FSO than non-ioECoG-tailored surgeries (OR 2.10 [95% CI 1.37-3.24]; p < 0.01; very low certainty). Complete resection of tissue that displayed IEDs in ioECoG predicted FSO better compared with incomplete resection (OR 3.04 [1.76-5.25]; p < 0.01; low certainty). We found insignificant difference in FSO after ioECoG-tailored surgery in children vs adults, TL vs eTL, or MRI-positive vs MRI-negative. The network meta-analysis showed that the odds of FSO was lower for malformations of cortical development than for tumors (OR 0.47 95% credible interval 0.25-0.87). DISCUSSION: Although limited by low-quality evidence, our meta-analysis shows a relatively good surgical outcome (74% FSO) after epilepsy surgery with ioECoG, especially in tumors, with better outcome for ioECoG-tailored surgeries in studies describing both and better outcome after complete removal of IED areas.

Systematic review of seizure-onset patterns in stereo-electroencephalography: Current state and future directions.

OBJECTIVE: Increasing evidence suggests that the seizure-onset pattern (SOP) in stereo-electroencephalography (SEEG) is important for localizing the "true" seizure onset. Specifically, SOPs with low-voltage fast activity (LVFA) are associated with seizure-free outcome (Engel I). However, several classifications and various terms corresponding to the same pattern have been reported, challenging its use in clinical practice. METHOD: Following the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guideline, we performed a systematic review of studies describing SOPs along with accompanying figures depicting the reported SOP in SEEG. RESULTS: Of 1799 studies, 22 met the selection criteria. Among the various SOPs, we observed that the terminology for low frequency periodic spikes exhibited the most variability, whereas LVFA is the most frequently used term of this pattern. Some SOP terms were inconsistent with standard EEG terminology. Finally, there was a significant but weak association between presence of LVFA and seizure-free outcome. CONCLUSION: Divergent terms were used to describe the same SOPs and some of these terms showed inconsistencies with the standard EEG terminology. Additionally, our results confirmed the link between patterns with LVFA and seizure-free outcomes. However, this association was not strong. SIGNIFICANCE: These results underline the need for standardization of SEEG terminology.

The predictive value of heart rate in determining clinical course after a bupropion overdose.

INTRODUCTION: Bupropion is a popular antidepressant due to its favorable side effect profile and indications for smoking cessation and weight loss. Due to the possibility of delayed onset seizure and other adverse outcomes after bupropion overdose, patients are often observed for periods of 12-24 hours following suspected ingestion. Tachycardia is a clinical predictor that holds promise in differentiating cases at risk for seizures from low-risk cases that do not require prolonged observation. This study assessed whether heart rate within the first eight hours of presentation can identify cases that do not require extended observation. METHODS: This is a retrospective cohort study of all supra-therapeutic bupropion cases from two hospital systems between 2010 and 2022. RESULTS: Data from 216 charts were included. Seizures, hypotension, and dysrhythmias occurred in 19 percent (n = 41), 1.4 percent (n = 3), 0.9 percent (n = 2) respectively. One patient died. Delayed adverse effects were rare (n = 4); they occurred from 14 hours to 28 hours post-ingestion. Maximum heart rate in eight hours was associated with a risk of adverse outcomes. (odds ratio, 1.07; 95 percent confidence interval: 1.05 to 1.09; P < 0.001). An eight hour maximum heart rate threshold of 104 beats/minute had a negative predictive value of 100 percent (95 percent confidence interval: 96.7 percent to 100 percent) for the occurrence of delayed adverse effects. All patients with delayed effects had tachycardia within five hours of emergency department arrival. DISCUSSION: Delayed adverse outcomes of seizures, hypotension, dysrhythmia, and death were uncommon in this cohort. Heart rate during the first eight hours of observation performs reliably as a screening test to identify patients at low risk for delayed adverse outcomes. This study is limited by its retrospective nature, the inability to ascertain time of ingestion for most cases and the lack of confirmatory laboratory testing. CONCLUSION: This study supports the use of an eight hour observation period when there are no other clinical signs of toxicity to warrant admission and if no co-ingestion or administration of substances that mask tachycardia are present.

Variation in neuroimaging and outcomes in patients with Sturge Weber syndrome Type III.

OBJECTIVES: Sturge Weber syndrome (SWS) is a neurovascular condition with an estimated incidence of 1 in 20,000 to 50,000 live births. SWS Types I and II involve cutaneous and ophthalmological findings, with neurological involvement in Type I. SWS Type III is exclusive to brain stigmata. Our study aims to describe the characteristics of brain MRI findings and report neuroradiological features with seizure and cognitive outcomes in patients with SWS Type III. METHODS: This is a retrospective case series examining the clinical, radiological, and cognitive characteristics of patients with SWS Type III referred to the SWS Clinic at Boston Children's Hospital. We analyzed brain MRI findings based on vascular and parenchymal features. Clinical and cognitive outcomes were based on a validated assessment tool in this population (Neuroscore). RESULTS: This dedicated case series of patients with Type III SWS from a single center identified ten patients. All patients had classic stigmata indicative of SWS. Two distinct radiological phenotypes were found, one characterized by more pronounced deep venous enlargement, and the other, with more pronounced parenchymal abnormalities. There was heterogeneity in seizure presentation and outcome. Earlier age of onset and seizures predict more severe outcomes, as seen in classic SWS. CONCLUSION: We could not find significant divergence in outcomes between patients with differing neuroimaging phenotypes. These results raise the question of whether the two distinct radiological phenotypes found in SWS Type III are reflective of different disease entities, with underlying genetic heterogeneity. These results suggest the need for larger, multi-center natural history studies.

Control of seizure-like dynamics in neuronal populations with excitability adaptation related to ketogenic diet.

We consider a heterogeneous, globally coupled population of excitatory quadratic integrate-and-fire neurons with excitability adaptation due to a metabolic feedback associated with ketogenic diet, a form of therapy for epilepsy. Bifurcation analysis of a three-dimensional mean-field system derived in the framework of next-generation neural mass models allows us to explain the scenarios and suggest control strategies for the transitions between the neurophysiologically desired asynchronous states and the synchronous, seizure-like states featuring collective oscillations. We reveal two qualitatively different scenarios for the onset of synchrony. For weaker couplings, a bistability region between the lower- and the higher-activity asynchronous states unfolds from the cusp point, and the collective oscillations emerge via a supercritical Hopf bifurcation. For stronger couplings, one finds seven co-dimension two bifurcation points, including pairs of Bogdanov-Takens and generalized Hopf points, such that both lower- and higher-activity asynchronous states undergo transitions to collective oscillations, with hysteresis and jump-like behavior observed in vicinity of subcritical Hopf bifurcations. We demonstrate three control mechanisms for switching between asynchronous and synchronous states, involving parametric perturbation of the adenosine triphosphate (ATP) production rate, external stimulation currents, or pulse-like ATP shocks, and indicate a potential therapeutic advantage of hysteretic scenarios.

Characterizing Frontal Lobe Seizure Semiology in Children.

OBJECTIVE: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. METHODS: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). RESULTS: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). INTERPRETATION: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.

The homeostatic effects of the RE-1 silencing transcription factor on cortical networks are altered under ictogenic conditions in the mouse.

AIM: The Repressor Element-1 Silencing Transcription Factor (REST) is an epigenetic master regulator playing a crucial role in the nervous system. In early developmental stages, REST downregulation promotes neuronal differentiation and the acquisition of the neuronal phenotype. In addition, postnatal fluctuations in REST expression contribute to shaping neuronal networks and maintaining network homeostasis. Here we investigate the role of the early postnatal deletion of neuronal REST in the assembly and strength of excitatory and inhibitory synaptic connections. METHODS: We investigated excitatory and inhibitory synaptic transmission by patch-clamp recordings in acute neocortical slices in a conditional knockout mouse model (RestGTi) in which Rest was deleted by delivering PHP.eB adeno-associated viruses encoding CRE recombinase under the control of the human synapsin I promoter in the lateral ventricles of P0-P1 pups. RESULTS: We show that, under physiological conditions, Rest deletion increased the intrinsic excitability of principal cortical neurons in the primary visual cortex and the density and strength of excitatory synaptic connections impinging on them, without affecting inhibitory transmission. Conversely, in the presence of a pathological excitation/inhibition imbalance induced by pentylenetetrazol, Rest deletion prevented the increase in synaptic excitation and decreased seizure severity. CONCLUSION: The data indicate that REST exerts distinct effects on the excitability of cortical circuits depending on whether it acts under physiological conditions or in the presence of pathologic network hyperexcitability. In the former case, REST preserves a correct excitatory/inhibitory balance in cortical circuits, while in the latter REST loses its homeostatic activity and may become pro-epileptogenic.

Measurable transitions during seizures in intracranial EEG: A stereoelectroencephalography and SPECT study.

OBJECTIVE: Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. METHODS: We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. RESULTS: Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. CONCLUSIONS: Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. SIGNIFICANCE: Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states.

Systematic 1 Hz direct electrical stimulation for seizure induction: A reliable method for localizing seizure onset zone and predicting seizure freedom.

OBJECTIVE: To prospectively investigate the utility of seizure induction using systematic 1 Hz stimulation by exploring its concordance with the spontaneous seizure onset zone (SOZ) and relation to surgical outcome; comparison with seizures induced by non-systematic 50 Hz stimulation was attempted as well. METHODS: Prospective cohort study from 2018 to 2021 with ≥ 1 y post-surgery follow up at Yale New Haven Hospital. With 1 Hz, all or most of the gray matter contacts were stimulated at 1, 5, and 10 mA for 30-60s. With 50 Hz, selected gray matter contacts outside of the medial temporal regions were stimulated at 1-5 mA for 0.5-3s. Stimulation was bipolar, biphasic with 0.3 ms pulse width. The Yale Brain Atlas was used for data visualization. Variables were analyzed using Fisher's exact, χ2, or Mann-Whitney test. RESULTS: Forty-one consecutive patients with refractory epilepsy undergoing intracranial EEG for localization of SOZ were included. Fifty-six percent (23/41) of patients undergoing 1 Hz stimulation had seizures induced, 83% (19/23) habitual (clinically and electrographically). Eighty two percent (23/28) of patients undergoing 50 Hz stimulation had seizures, 65% (15/23) habitual. Stimulation of medial temporal or insular regions with 1 Hz was more likely to induce seizures compared to other regions [15/32 (47%) vs. 2/41 (5%), p < 0.001]. Sixteen patients underwent resection; 11/16 were seizure free at one year and all 11 had habitual seizures induced by 1 Hz; 5/16 were not seizure free at one year and none of those 5 had seizures with 1 Hz (11/11 vs 0/5, p < 0.0001). No patients had convulsions with 1 Hz stimulation, but four did with 50 Hz (0/41 vs. 4/28, p = 0.02). SIGNIFICANCE: Induction of habitual seizures with 1 Hz stimulation can reliably identify the SOZ, correlates with excellent surgical outcome if that area is resected, and may be superior (and safer) than 50 Hz for this purpose. However, seizure induction with 1 Hz was infrequent outside of the medial temporal and insular regions in this study.

Why did my seizures start now? Influences of lesion connectivity and genetic etiology on age at seizure onset in focal epilepsy.

OBJECTIVE: Patients with focal, lesional epilepsy present with seizures at variable ages. Larger lesion size and overlap with sensorimotor or default mode network (DMN) have been associated with younger age at seizure onset in cohorts with mixed types of focal cortical dysplasia (FCD). Here, we studied determinants of age at seizure onset in patients with bottom-of-sulcus dysplasia (BOSD), a discrete type of FCD with highly localized epileptogenicity. METHODS: Eighty-four patients (77% operated) with BOSD were studied. Demographic, histopathologic, and genetic findings were recorded. BOSD volume and anatomical, primary versus association, rostral versus caudal, and functional network locations were determined. Normative functional connectivity analyses were performed using each BOSD as a region of interest in resting-state functional magnetic resonance imaging data of healthy children. Variables were correlated with age at seizure onset. RESULTS: Median age at seizure onset was 5.4 (interquartile range = 2-7.9) years. Of 50 tested patients, 22 had somatic and nine had germline pathogenic mammalian target of rapamycin (mTOR) pathway variants. Younger age at seizure onset was associated with greater BOSD volume (p = .002), presence of a germline pathogenic variant (p = .04), DMN overlap (p = .04), and increased functional connectivity with the DMN (p < .05, false discovery rate corrected). Location within sensorimotor cortex and networks was not associated with younger age at seizure onset in our relatively small but homogenous cohort. SIGNIFICANCE: Greater lesion size, pathogenic mTOR pathway germline variants, and DMN connectivity are associated with younger age at seizure onset in small FCD. Our findings strengthen the suggested role of DMN connectivity in the onset of FCD-related focal epilepsy and reveal novel contributions of genetic etiology.

Epileptic spasms in clusters without hypsarrhythmia in infancy and childhood: A single age-dependent type of epilepsy or well-defined epileptic syndrome?

OBJECTIVE: In this study, we present the electroclinical features and outcomes of 92 patients with epileptic spasms (ES) in clusters without modified or classical hypsarrhythmia that started in either in infancy or in childhood; we compared both groups in terms of electroclinical features, etiology, treatment, evolution, and outcome. METHODS: Between June 2000 and July 2022, 92 patients met the electroclinical diagnostic criteria of ES in clusters without hypsarrhythmia. Patients with ES associated with other epileptic encephalopathies including West Syndrome, as well as those with the specific etiology of ES and developmental and epileptic encephalopathy associated with CDKL5 were excluded. RESULTS: The patients were divided into two groups based on the age at ES onset: those with ES onset before (Group 1) and those with ES onset after 2 years of age (Group 2). The features of ES and the type of associated seizures before and after ES onset, as well as the interictal and ictal EEG and electromyography findings were similar in both groups. The etiologies were mainly structural (40.2%), genetic (11.9%), and unknown (44.6%) in majority of the patients in both groups. Thirty-one patients were seizure-free, while in the remaining patients the seizures continued. Nine patients (9.8%) with unilateral structural lesions underwent surgery with good results. The neurological abnormalities and developmental findings prior to ES onset depended on the underlying etiology. CONCLUSION: Our series of patients may represent a well-defined epileptic syndrome or type of epilepsy with onset in infancy or childhood characterized by ES in clusters without hypsarrhythmia associated with focal and generalized seizures and EEG paroxysms without neurological deterioration.

Minimum standards for inpatient long-term video-EEG monitoring: A clinical practice guideline of the international league against epilepsy and international federation of clinical neurophysiology.

The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long-term video-electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We found limited high-level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events (see Table S1). For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long-term outcome effects of LTVEM and establish its clinical utility.

Mesial Temporal Sclerosis as Late Consequence of Posterior Reversible Encephalopathy Syndrome in Pediatric Hemato-oncologic Patients.

OBJECTIVES: Drug resistant epilepsy has rarely been reported following posterior reversible encephalopathy syndrome (PRES), with few cases of mesial temporal sclerosis (MTS). The aim of this study was to report clinical and neuroimaging features of MTS subsequent to PRES in hemato-oncologic/stem cell transplanted children. MATERIALS AND METHODS: Among 70 children treated in 2 pediatric hemato-oncologic Italian centers between 1994 and 2018 and presenting an episode of PRES, we retrospectively identified and analyzed a subgroup of patients who developed epilepsy and MTS. RESULTS: Nine of 70 patients (12.8%) developed post-PRES persistent seizures with magnetic resonance imaging evidence of MTS. One patient died few months after MTS diagnosis, because of hematologic complications; the remaining 8 patients showed unprovoked seizures over time leading to the diagnosis of epilepsy, focal in all and drug resistant in 4. At PRES diagnosis, all patients with further evidence of epilepsy and MTS suffered of convulsive seizures, evolving into status epilepticus in 3. In 3 patients a borderline cognitive level or intellectual disability were diagnosed after the onset of epilepsy, and 2 had behavioral problems impacting their quality of life. CONCLUSIONS: MTS and long-term focal epilepsy, along with potential cognitive and behavioral disorders, are not uncommon in older pediatric patients following PRES.

Relationship between location of epileptic focus and occurrence during sleep versus wakefulness.

Different sleep stages exert differential effects on interictal discharges, neural synchrony and seizure threshold. We sought to assess the relationship between localization of the epileptogenic focus and seizure distribution in sleep versus wakefulness among patients with refractory epilepsy. We conducted a retrospective chart review-based study. Video-electroencephalography of patients with refractory epilepsy, planned for resective surgery, were reviewed for seizure localisation and occurrence relative to stage of sleep/wakefulness. Demographic/clinical data, including details of surgery, were also recorded. Bivariate analysis was conducted using the chi-square test for proportions and unpaired t-test/ANOVA to compare the means within groups. We enrolled 175 patients (107 males) with a mean age of 26.1 + 9.8 years (range: 4-53 years). We analysed 1,282 seizures, of which 916 (71.5%) were temporal, 95 (7.4%) frontal, 144 (11.2 %) central/ parietal and 19 (1.5%) arose from the occipital lobe. Temporal lobe onset seizures were more frequent during wakefulness (77.7%) compared to extra-temporal localization (65%) (p<0.0001). Amongst temporal lobe onset seizures, those during wakefulness arose more frequently from the lateral temporal (88.6%) compared to the mesial temporal lobe (75.5%) (p=0.0003). A higher proportion of seizures evolved into secondary generalisation during sleep (23.5%) versus 8.7% during wakefulness (p<0.0001). Our study demonstrates that lobar location of epileptogenic foci is associated with a predilection of seizures to occur, as well as secondarily generalise, during sleep/wakefulness. Seizures with lateral temporal lobe as well as extratemporal lobe onset were more likely to occur during wakefulness. Overall, sleep related seizures were more likely to be of extratemporal lobe onset, though.

Children with seizures and radiological diagnosis of focal cortical dysplasia: can drug-resistant epilepsy be predicted earlier?

OBJECTIVE: Focal cortical dysplasia (FCD) is a malformation of cortical development and is associated with drug-resistant epilepsy. Standard indication for epilepsy surgery is drug resistance (as defined by the ILAE). Given the high incidence of drug resistance in these children, this delay may not be warranted. The aim of the study was to determine the proportion of patients with a presumed FCD who develop drug resistance, and evaluate post-operative outcomes. METHODS: This study incorporated a survey within a regional paediatric epilepsy network and a retrospective database review of a paediatric epilepsy centre serving the network to identify children with epilepsy and a presumed FCD on MRI. RESULTS: The survey revealed that 86% of the patients with epilepsy and presumed FCD on MRI within the network were referred to our centre. Of 139 paediatric patients included in the study, 131 (94.2%) had drug-resistant epilepsy. One hundred and ten (83.9%) patients were referred to epilepsy surgery, of whom 97 underwent surgery. Of 92 with one-year postoperative follow-up, 59.8% had an Engel Class 1 (seizure-free) outcome. Concordance of location between MRI and ictal EEG was strongly associated with Engel Class 1 outcome (p<0.001), as was older age at seizure onset (p=0.03). Time from diagnosis to surgery, number of medications, type of surgery and histology were not associated with improved outcome. SIGNIFICANCE: Our data suggest that most children presenting with seizures and a radiological diagnosis of FCD will develop drug-resistant epilepsy and are candidates for epilepsy surgery. The main outcome predictors are the correlation between MRI and ictal EEG localization and age at onset. This suggests that patients with FCD and epilepsy may be considered for surgery before traditional criteria of drug resistance are met. This change in practice has the potential to improve quality of life and cognitive function, and reduce burden on epilepsy services.

Glioma-related epilepsy in patients with diffuse high-grade glioma after the 2016 WHO update: seizure characteristics, risk factors, and clinical outcomes.

OBJECTIVE: The aim of this study was to investigate the epidemiological characteristics, associated risk factors, and prognostic value of glioma-related epilepsy in patients with diffuse high-grade gliomas (DHGGs) that were diagnosed after the 2016 updated WHO classification was released. METHODS: Data from 449 patients with DHGGs were retrospectively collected. Definitive diagnosis was reaffirmed according to the 2016 WHO classification. Seizure outcome was assessed using the Engel classification at 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors associated with preoperative and postoperative glioma-related epilepsy. Lastly, the prognostic value of glioma-related epilepsy was evaluated by Kaplan-Meier and Cox analysis. RESULTS: The incidence of glioma-related epilepsy decreased gradually as the malignancy of the tumor increased. Age < 45 years (OR 2.601, p < 0.001), normal neurological function (OR 3.024, p < 0.001), and lower WHO grade (OR 2.028, p = 0.010) were independently associated with preoperative glioma-related epilepsy, while preoperative glioma-related epilepsy (OR 7.554, p < 0.001), temporal lobe involvement (OR 1.954, p = 0.033), non-gross-total resection (OR 2.286, p = 0.012), and lower WHO grade (OR 2.130, p = 0.021) were identified as independent predictors of poor seizure outcome. Furthermore, postoperative glioma-related epilepsy, rather than preoperative glioma-related epilepsy, was demonstrated as an independent prognostic factor for overall survival (OR 0.610, p = 0.010). CONCLUSIONS: The updated WHO classification seems conducive to reveal the distribution of glioma-related epilepsy in DHGG patients. For DHGG patients with high-risk predictors of poor seizure control, timely antiepileptic interventions could be beneficial. Moreover, glioma-related epilepsy (especially postoperative glioma-related epilepsy) is associated with favorable overall survival.

Determinants of postictal agitation and recovery after tonic-clonic seizures in generalized and focal epilepsy.

OBJECTIVE: The postictal state after bilateral tonic-clonic seizures is often prolonged and can have significant impact on a patient's quality of life. Considerable variability exists in the magnitude of postictal agitation and in the speed of recovery, the determinants of which are not well understood. We studied postictal behavior after tonic-clonic seizures in various epilepsy localizations, focusing on postictal agitation and time to responsiveness. METHODS: We retrospectively identified 15 adult patients each with idiopathic generalized, left temporal lobe, right temporal lobe and frontal lobe epilepsy. Localization in focal epilepsy was validated by good outcome after resective surgery at one-year of follow-up. The first tonic-clonic seizure with reliable video and EEG for each patient was analyzed by two reviewers, one of whom was blinded to clinical data. Clinical, ictal and postictal variables were collected for each patient and analyzed. Postictal agitation was classified as mild and marked. RESULTS: We reviewed 60 tonic-clonic seizures, 15 in each of four patient groups. Postictal agitation was observed in 14 patients (23.3%; marked in one and mild in 13). Postictal agitation was most common in patients with left temporal (seven patients) and least common in idiopathic generalized epilepsy (one patient) groups (p=0.035). Based on subgroup analysis (n=28), time to responsiveness was 6.6 minutes for frontal, 7.2 minutes for generalized, 10 minutes for right temporal and 15.7 minutes for the left temporal groups (p<0.05 for frontal vs. left temporal, generalized vs. left temporal). Time to responsiveness was longer in patients with agitation than without (13.9 minutes vs. 7.7 minutes; p=0.048). Patient ictal and postictal characteristics demonstrated no relationship to agitation or latency to postictal recovery. SIGNIFICANCE: To mitigate harm, patients must be monitored carefully after tonic-clonic seizures, especially patients with left temporal lobe epilepsy. Studies evaluating medical and behavioral interventions to promote postictal recovery are needed.

Viral expression of constitutively active AKT3 induces CST axonal sprouting and regeneration, but also promotes seizures.

Increasing the intrinsic growth potential of neurons after injury has repeatedly been shown to promote some level of axonal regeneration in rodent models. One of the most studied pathways involves the activation of the PI3K/AKT/mTOR pathways, primarily by reducing the levels of PTEN, a negative regulator of PI3K. Likewise, activation of signal transducer and activator of transcription 3 (STAT3) has previously been shown to boost axonal regeneration and sprouting within the injured nervous system. Here, we examined the regeneration of the corticospinal tract (CST) after cortical expression of constitutively active (ca) Akt3 and STAT3, both separately and in combination. Overexpression of caAkt3 induced regeneration of CST axons past the injury site independent of caSTAT3 overexpression. STAT3 demonstrated improved axon sprouting compared to controls and contributed to a synergistic improvement in effects when combined with Akt3 but failed to promote axonal regeneration as an individual therapy. Despite showing impressive axonal regeneration, animals expressing Akt3 failed to show any functional improvement and deteriorated with time. During this period, we observed progressive Akt3 dose-dependent increase in behavioral seizures. Histology revealed increased phosphorylation of ribosomal S6 protein within the unilateral cortex, increased neuronal size, microglia activation and hemispheric enlargement (hemimegalencephaly).