Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

Safety of Concomitant Cortical and Thalamic Stereoencephalography Explorations in Patients With Drug-Resistant Epilepsies.

BACKGROUND AND OBJECTIVES: Intracranial electrophysiology of thalamic nuclei has demonstrated involvement of thalamic areas in the propagation of seizures in focal drug-resistant epilepsy. Recent studies have argued that thalamus stereoencephalography (sEEG) may aid in understanding the epileptogenic zone and treatment options. However, the study of thalamic sEEG-associated hemorrhage incidence has not been investigated in a cohort study design. In this article, we present the largest retrospective cohort study of sEEG patients and compare hemorrhage rates between those with and without thalamic sEEG monitoring. METHODS: Retrospective chart review of clinical and epilepsy history, electrode implantation, rationale, and outcomes was performed for 76 patients (age 20-69 years) with drug-resistant epilepsy who underwent sEEG monitoring at our institution (2019-2022). A subset of 38% of patients (n = 30) underwent thalamic monitoring of the anterior thalamic nucleus (n = 14), pulvinar nucleus (n = 25), or both (n = 10). Planned perisylvian orthogonal sEEG trajectories were extended to 2- to 3-cm intraparenchymally access thalamic area(s).The decision to incorporate thalamic monitoring was made by the multidisciplinary epilepsy team. Statistical comparison of hemorrhage rate, type, and severity between patients with and without thalamic sEEG monitoring was made. RESULTS: Our approach for thalamic monitoring was not associated with local intraparenchymal hemorrhage of thalamic areas or found along extended cortical trajectories, and symptomatic hemorrhage rates were greater for patients with thalamic coverage (10% vs 0%, P = .056), although this was not found to be significant. Importantly, patients with perisylvian electrode trajectories, with or without thalamic coverage, did not experience a higher incidence of hemorrhage (P = .34). CONCLUSION: sEEG of the thalamus is a safe and valuable tool that can be used to interrogate the efficacy of thalamic neuromodulation for drug-resistant epilepsy. While patients with thalamic sEEG did have higher incidence of hemorrhage at any monitoring site, this finding was apparently not related to the method of perisylvian implantation and did not involve any trajectories targeting the thalamus.

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

Arteries Around the Superior Limiting Sulcus: Motor Complication Avoidance in Insular and Insulo-Opercular Surgery.

BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

Dynamics of AMPA receptors regulate epileptogenesis in patients with epilepsy.

The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.

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.

Is Hippocampal Resection Necessary for Low-Grade Epilepsy-Associated Tumors in the Temporal Lobe?

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

Rigorous mathematical formulation of net escape velocity and net escape probability determining a macroscopic concentration.

Net escape velocity (NEV) and net escape probability (NEP) are concepts that describe that scalar quantity discharged from a source in an indoor air environment is expressed by the unique velocity scales of the returning and escaping populations. Despite the conceptual description and applications of several numerical simulations, the definitions were not precisely explained using a mathematical formula. Here, we derive rigorous mathematical formulations of the NEV and NEP. These formulations provide us with the physical interpretation of NEV, clarify the sufficient condition of perfect escape, and lead to a further formulation of the transfer probability of the scalar. To justify and apply the derived relationships, two simple problems were numerically solved: One was a diffusion equation, and the other was an advection-diffusion equation. The results of the diffusion problem clearly demonstrate that only the outgoing scalar flux exists on the surface of the control volume, covering the source at any location. In contrast, the advection-diffusion problem reveals that there is a returning population of the scalar in most locations, despite both diffusion and turbulent parts working to remove the scalar. This rigorous formulation contributes to apply NEV as an appropriate air quality index with the clear physical interpretation to determine the local scalar concentration.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Availability of tracheal shift in the chest X-ray image as pre-treatment evaluation of mechanical thrombectomy.

BACKGROUND: The use of mechanical thrombectomy (MT) for treatment of acute large vessel occlusion has recently increased. Prompt and timely guiding catheter (GC) induction is necessary to improve prognosis of MT and reduce the time for recanalization. However, difficulties in GC induction are encountered in some patients. This GC induction depends mainly on the aortic arch structure. Therefore, this study focused on assessing presence of tracheal shift on chest X-ray images as pre-treatment evaluation method for GC induction due to its wide availability as an indicator for status of the mediastinum. METHODS: We retrospectively examined 33 patients who underwent MT at our facilities between April 2017 and March 2021. The patients were divided into two groups according to presence or absence of tracheal shift on chest X-ray images. Background characteristics and treatment courses in these two groups were compared. RESULTS: Among 33 patients, tracheal shift was observed on the chest X-ray images of 14 patients. Furthermore, tracheal shift was positively correlated with the time of GC induction (32.9 min vs. 11.6 min, [p < 0.05]) and the female sex (p = 0.03). Additionally, tracheal shift exhibited correlations with multiple risk factors of atherosclerosis (p = 0.04). CONCLUSIONS: In patients with tracheal shift, GC induction could be expectedly difficult. Therefore, advanced disinfection of the right upper arm and affected side of the neck during MT in preparation for changing an approach route is required.

Epileptic discharges initiate from brain areas with elevated accumulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors.

Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor is a major component of neurotransmission. Although elevated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated currents initiate epileptic discharges. We have recently developed the first PET tracer for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, [11C]K-2, to visualize and quantify the density of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.

HSP90 Inhibition Overcomes Resistance to Molecular Targeted Therapy in BRAFV600E-mutant High-grade Glioma.

PURPOSE: Molecular targeted therapy using BRAF and/or MEK inhibitors has been applied to BRAFV600E-mutant high-grade gliomas (HGG); however, the therapeutic effect is limited by the emergence of drug resistance. EXPERIMENTAL DESIGN: We established multiple paired BRAFV600E-mutant HGG patient-derived xenograft models based on tissues collected prior to and at relapse after molecular targeted therapy. Using these models, we dissected treatment-resistant mechanisms for molecular targeted therapy and explored therapeutic targets to overcome resistance in BRAFV600E HGG models in vitro and in vivo. RESULTS: We found that, despite causing no major genetic and epigenetic changes, BRAF and/or MEK inhibitor treatment deregulated multiple negative feedback mechanisms, which led to the reactivation of the MAPK pathway through c-Raf and AKT signaling. This altered oncogenic signaling primarily mediated resistance to molecular targeted therapy in BRAFV600E-mutant HGG. To overcome this resistance mechanism, we performed a high-throughput drug screening to identify therapeutic agents that potently induce additive cytotoxicity with BRAF and MEK inhibitors. We discovered that HSP90 inhibition combined with BRAF/MEK inhibition coordinately deactivated the MAPK and AKT/mTOR pathways, and subsequently induced apoptosis via dephosphorylation of GSK3ß (Ser9) and inhibition of Bcl-2 family proteins. This mediated potent cytotoxicity in vitro and in vivo in refractory models with acquired resistance to molecular targeted therapy. CONCLUSIONS: The combination of an HSP90 inhibitor with BRAF or MEK inhibitors can overcome the limitations of the current therapeutic strategies for BRAFV600E-mutant HGG.

Relaxin exerts a protective effect during ischemia-reperfusion in the rat model.

BACKGROUND: Testicular torsion, which causes ischemia-reperfusion (IR) injury, is a serious urological emergency that can lead to testicular dysfunction, including infertility, primarily among newborn and pubertal males; thus, effective drugs should be administered during or after ischemia. OBJECTIVES: Using a rat model of testicular IR injury, the present study investigated the protective effects of relaxin (RLN) against oxidative stress, testicular dysfunction, inflammation, histological damage, arrested spermatogenesis, and germ cell apoptosis as well as explored the usefulness of RLN as a potential protective drug for IR injury combined with surgical treatment. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to left testicular ischemia for 2 h, followed by 24 h of reperfusion. They were subsequently divided into three groups: sham, IR, and IR + RLN groups. Porcine RLN (500 ng/h) or saline was infused using an implanted osmotic mini-pump 90 min after inducing ischemia. The RLN dose used herein was that which resulted in serum RLN levels comparable to those in mid-pregnant rats based on previous studies. RESULTS: Testicular IR increased germ cell apoptosis and histological damage as well as promoted disorganized and arrested spermatogenesis, accompanied by a significant increase in oxidative stress and inflammation. However, RLN administration ameliorated the adverse consequences associated with IR injury by attenuating oxidative stress and mitigating apoptosis and inflammation. DISCUSSION AND CONCLUSION: The study findings clearly demonstrated that RLN exerts a protective effect against IR-induced testicular injury by attenuating oxidative stress, apoptosis, and inflammation, suggesting that RLN together with surgical treatment is a potentially efficacious approach toward ameliorating testicular dysfunction following testicular torsion.

Barriers to telemedicine among physicians in epilepsy care during the COVID-19 pandemic: A national-level cross-sectional survey in Japan.

OBJECTIVE: This study aimed to investigate the factors affecting the unwillingness of physicians involved in epilepsy care to continue telemedicine during the coronavirus disease 2019 (COVID-19) pandemic in Japan. METHOD: This was a national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan) which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES). We asked physicians who conducted telemedicine in patients with epilepsy (PWE) during the COVID-19 pandemic at four clinics and 21 hospitals specializing in epilepsy care in Japan from March 1 to April 30, 2021. The following data were collected: (1) participant profile, (2) characteristics of PWE treated by telemedicine, and (3) contents and environmental factors of telemedicine. Statistically significant variables (p < 0.05) in the univariate analysis were analyzed in a multivariate binary logistic regression model to detect the independently associated factors with the unwillingness to continue telemedicine. RESULT: Among the 115 respondents (response rate: 64%), 89 were included in the final analysis. Of them, 60 (67.4%) were willing to continue telemedicine, and 29 (32.6%) were unwilling. In the univariate binary logistic regression analysis, age (Odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.10-3.09, p = 0.02), psychiatrist (OR = 5.88, 95% CI 2.15-16.08, p = 0.001), hospital (OR = 0.10, 95% CI 0.01-0.94, p = 0.04), the number of COVID-19 risk factors in the participant (OR = 2.88, 95% CI 1.46-5.69, p = 0.002), the number of COVID-19 risk factors in the cohabitants (OR = 2.52, 95% CI 1.05-6.01, p = 0.04), COVID-19 epidemic area (OR = 4.37, 95% CI 1.18-16.20, p = 0.03), consultation time during telemedicine (OR = 2.51, 95% CI 1.32-4.76, p = 0.005), workload due to telemedicine (OR = 4.17, 95% CI 2.11-8.24, p < 0.001) were statistically significant. In the multivariate binary logistic regression analysis, workload due to telemedicine (OR = 4.93, 95% CI 1.96-12.35) was independently associated with the unwillingness to continue telemedicine. CONCLUSION: This national-level cross-sectional survey found that workload due to telemedicine among physicians involved in epilepsy care was independently associated with the unwillingness to continue telemedicine.

Risk factors for psychological distress in electroencephalography technicians during the COVID-19 pandemic: A national-level cross-sectional survey in Japan.

OBJECTIVE: To identify the risk factors for psychological distress in electroencephalography (EEG) technicians during the coronavirus disease 2019 (COVID-19) pandemic. METHOD: In this national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan), which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES), a questionnaire was administered to 173 technicians engaged in EEG at four clinics specializing in epilepsy care and 20 hospitals accredited as (quasi-) epilepsy centers or epilepsy training facilities in Japan from March 1 to April 30, 2021. We collected data on participants' profiles, information about work, and psychological distress outcome measurements, such as the K-6 and Tokyo Metropolitan Distress Scale for Pandemic (TMDP). Linear regression analysis was used to identify the risk factors for psychological distress. Factors that were significantly associated with psychological distress in the univariate analysis were subjected to multivariate analysis. RESULTS: Among the 142 respondents (response rate: 82%), 128 were included in the final analysis. As many as 35.2% of EEG technicians have been under psychological distress. In multivariate linear regression analysis for K-6, female sex, examination for patients (suspected) with COVID-19, and change in salary or bonus were independent associated factors for psychological distress. Contrastingly, in multivariate linear regression analysis for TMDP, female sex, presence of cohabitants who had to be separated from the respondent due to this pandemic, and change in salary or bonus were independent associated factors for psychological distress. CONCLUSION: We successfully identified the risk factors associated with psychological distress in EEG technicians during the COVID-19 pandemic. Our results may help in understanding the psychological stress in EEG technicians during the COVID-19 pandemic and improving the work environment, which is necessary to maintain the mental health of EEG technicians.

Epilepsy surgery in children under 3 years of age: surgical and developmental outcomes.

OBJECTIVE: Pediatric epilepsy surgery is known to be effective, but early surgery in infancy is not well characterized. Extensive cortical dysplasia, such as hemimegalencephaly, can cause refractory epilepsy shortly after birth, and early surgical intervention is indicated. However, the complication rate of early pediatric surgery is significant. In this study, the authors assessed the risk-benefit balance of early pediatric epilepsy surgery as relates to developmental outcomes. METHODS: This is a retrospective descriptive study of 75 patients who underwent their first curative epilepsy surgery at an age under 3 years at the authors' institution between 2006 and 2019 and had a minimum 1-year follow-up of seizure and developmental outcomes. Clinical information including surgical complications, seizure outcomes, and developmental quotient (DQ) was collected from medical records. The effects of clinical factors on DQ at 1 year after surgery were evaluated. RESULTS: The median age at surgery was 6 months, peaking at between 3 and 4 months. Operative procedures included 27 cases of hemispherotomy, 19 cases of multilobar surgery, and 29 cases of unilobar surgery. Seizure freedom was achieved in 82.7% of patients at 1 year and in 71.0% of patients at a mean follow-up of 62.8 months. The number of antiseizure medications (ASMs) decreased significantly after surgery, and 19 patients (30.6%) had discontinued their ASMs by the last follow-up. Postoperative complications requiring cerebrospinal fluid (CSF) diversion surgery, such as hydrocephalus and cyst formation, were observed in 13 patients (17.3%). The mean DQ values were 74.2 ± 34.3 preoperatively, 60.3 ± 23.3 at 1 year after surgery, and 53.4 ± 25.1 at the last follow-up. Multiple regression analysis revealed that the 1-year postoperative DQ was significantly influenced by preoperative DQ and postoperative seizure freedom but not by the occurrence of any surgical complication requiring CSF diversion surgery. CONCLUSIONS: Early pediatric epilepsy surgery has an acceptable risk-benefit balance. Seizure control after surgery is important for postoperative development.

Single-Institutional Experience of Chronic Intracranial Electroencephalography Based on the Combined Usage of Subdural and Depth Electrodes.

Implantation of subdural electrodes on the brain surface is still widely performed as one of the "gold standard methods" for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. However, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.

IDH-Mutant Astrocytoma With Chromosome 19q13 Deletion Manifesting as an Oligodendroglioma-Like Morphology.

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.