Total Corpus Callosotomy via Posterior Approach with Endoscopic-Alone Technique.

Two main surgical techniques are available for corpus callosotomy (CC): conventional microscopic CC and endoscopic CC.1 Microscopic CC is more familiar to neurosurgeons and allows three-dimensional visualization, but it requires a larger craniotomy and has a narrower visual angle in the deep part. Endoscopic CC has only recently been introduced to epilepsy surgery, but it is gaining increasing interest among epilepsy surgeons. The endoscope provides two-dimensional visualization and requires a camera as an additional instrument inserted into the surgical corridor. The merits of endoscopic CC include the smaller craniotomy and smaller skin incision, potentially reducing invasiveness.2 Bridging veins to the superior sagittal sinus are also less problematic because of the reduced need for brain retraction. The lack of need of arachnoid dissection is another advantage. Generally, an anterior approach is applied for CC, but this approach makes interhemispheric fissure dissection mandatory, especially at the cingulate gyri. In some cases, this procedure can take a long time. On the other hand, a posterior approach requires less interhemispheric arachnoid dissection, or sometimes none at all, due to the anatomy of the falx cerebri. These reasons have driven the development of a posterior approach for an endoscopic-alone technique.3 Here, we present a 5-year-old girl with medically intractable epileptic spasms that were diagnosed as infantile epileptic spasms syndrome, who underwent endoscopic total CC via a posterior approach to control her seizures (Video 1).

Intraparenchymal and Subarachnoid Hemorrhage in Stereotactic Electroencephalography Caused by Indirect Adjacent Arterial Injury: Illustrative Case.

The complication rate of stereotactic electroencephalography (SEEG) is generally low, but various types of postoperative hemorrhage have been reported. We presented an unusual hemorrhagic complication after SEEG placement. A 20-year-old man presented with suspected frontal lobe epilepsy. We implanted 11 SEEG electrodes in the bilateral frontal lobes and the left insula. Computed tomography after implantation showed intraparenchymal hemorrhage in the left temporal lobe and insula and subarachnoid hemorrhage in the left Sylvian cistern. Later, the point of vessel injury was revealed from the identification of a pseudoaneurysm, but this location was not along the planned or actual electrode trajectory. The cause of hemorrhage was suggested to be indirect injury from stretching of the arachnoid trabeculae by the puncture needle.

Quantitative pretreatment EEG predicts efficacy of ACTH therapy in infantile epileptic spasms syndrome.

OBJECTIVE: This study aimed to determine the correlation between outcomes following adrenocorticotrophic hormone (ACTH) therapy and measurements of relative power spectrum (rPS), weighted phase lag index (wPLI), and graph theoretical analysis on pretreatment electroencephalography (EEG) in infants with non-lesional infantile epileptic spasms syndrome (IESS). METHODS: Twenty-eight patients with non-lesional IESS were enrolled. Outcomes were classified based on seizure recurrence following ACTH therapy: seizure-free (F, n = 21) and seizure-recurrence (R, n = 7) groups. The rPS, wPLI, clustering coefficient, and betweenness centrality were calculated on pretreatment EEG and were statistically analyzed to determine the correlation with outcomes following ACTH therapy. RESULTS: The rPS value was significantly higher in the delta frequency band in group R than in group F (p < 0.001). The wPLI values were significantly higher in the delta, theta, and alpha frequency bands in group R than in group F (p = 0.007, <0.001, and <0.001, respectively). The clustering coefficient in the delta frequency band was significantly lower in group R than in group F (p < 0.001). CONCLUSIONS: Our findings demonstrate the significant differences in power and functional connectivity between outcome groups. SIGNIFICANCE: This study may contribute to an early prediction of ACTH therapy outcomes and thus help in the development of appropriate treatment strategies.

Lacosamide monotherapy for the treatment of childhood epilepsy with centrotemporal spikes.

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) is known as age-limited focal epilepsy syndrome in childhood. Lacosamide is a third-generation antiepileptic drug. This study aimed to evaluate the efficacy of lacosamide monotherapy for the treatment of CECTS. METHODS: We enrolled 18 patients (6 girls and 12 boys) who met the following criteria: 1) the age of onset of the seizures was between 3 and 13 years of age; 2) showing at least hemifacial and/or oropharyngeal seizures; 3) interictal discharges in central and/or middle temporal electrodes; 4) no intellectual disability; 5) treatment duration of lacosamide monotherapy over 6 months. We retrospectively collected and analyzed clinical data and treatment information. We evaluated the seizure occurrences during 0-3, 4-6, and 7-12 months from the treatment initiation and the last 6 months of the follow-up. We also evaluated the outcomes as seizure-free if the patients developed no seizures both over 6 months and 3 times of pretreatment mean seizure interval at the last follow-up. RESULTS: Of the patients, 39%, 67% and 72% were seizure-free during 0-3, 4-6, and 7-12 months from treatment initiation, respectively. Finally, 83% of the patients achieved seizure freedom. Seizure freedom was achieved in 72% during the first 4 months of treatment. All patients continued lacosamide monotherapy during the study, although four patients showed transient fatigue or somnolence. CONCLUSIONS: Lacosamide showed good efficacy for controlling seizures with fewer adverse effects, and therefore may be a good candidate as a first-line medication for the treatment of new-onset CECTS.

Child Neurology: Pathologically Confirmed Thrombotic Microangiopathy Caused by Onasemnogene Abeparvovec Treatment for SMA.

Onasemnogene abeparvovec is an adeno-associated virus vector-based gene therapy for spinal muscular atrophy (SMA). Although several cases of drug-induced thrombotic microangiopathy due to onasemnogene abeparvovec have been reported, none has been confirmed pathologically. Here, we present renal histopathologic findings of TMA due to onasemnogene abeparvovec. On day 5 after receiving onasemnogene abeparvovec, a 23-month-old girl with SMA type 1 developed thrombocytopenia, microangiopathic hemolytic anemia, liver dysfunction, acute kidney injury, and hypertension. She was diagnosed with TMA and received an increased dose of prednisolone, antihypertensives, diuretics, packed red blood cell and platelet transfusion, a single dose of eculizumab, 4 cycles of plasmapheresis, and intermittent and continuous hemodialysis. Her TMA resolved by day 30. On day 49, renal biopsy was performed. Light microscopy revealed proliferation of glomerular mesangial cells and matrix, with mesangiolysis, endothelial cell swelling, and partial double contours of the glomerular basement membrane. Electron microscopy showed endothelial injury, with edematous changes of the subendothelial spaces and neoformation of the basement membrane, without electron-dense depositions. These findings are compatible with the recovery phase of TMA. One year after drug administration, her motor function is improved. She can hold her posture against gravity and has neither dysphagia nor respiratory disturbance, but mild hypertension persists. Physicians should be vigilant regarding TMA as a severe side effect of onasemnogene abeparvovec treatment, especially when thrombocytopenia, hemolytic anemia, increased lactate dehydrogenase, or acute kidney injury is present.

Comparative Effects of Sulforaphane and Allyl Isothiocyanate on 3T3-L1 Adipogenesis.

Sulforaphane and allyl isothiocyanate, naturally occurring isothiocyanates, have been reported to inhibit adipocyte differentiation, but little is known about how they compare in terms of their potency and mechanism of action. In the present study, we compared the effects of sulforaphane and allyl isothiocyanate on the differentiation of 3T3-L1 preadipocytes. A mixture of insulin, dexamethasone, and 3-isobutyl-1-methylxanthine was used to establish a differentiation medium. We found that, at a concentration as low as one-tenth that of allyl isothiocyanate, sulforaphane reduced triacylglycerol levels, lipid-filled adipocyte quantity, and mRNA and protein levels of CCAAT-enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ). These results suggested that sulforaphane may be a more potent adipocyte differentiation inhibitor than allyl isothiocyanate. Our results may provide insight into possible strategies for the prevention of obesity and related conditions.

Disconnection surgery to cure or palliate medically intractable epileptic spasms: a retrospective study.

OBJECTIVE: Surgery is a treatment option for medically intractable epileptic spasms (ESs). However, outcomes of ES after surgery are not well understood, especially when surgeries aimed at seizure palliation are included. The purpose of the present study was to 1) investigate the proportion of favorable postoperative ES outcomes, 2) explore the preoperative factors related to favorable postoperative ES outcomes, and 3) examine the timing of ES recurrence after disconnection surgeries, including both curative and palliative indications. METHODS: This retrospective study included patients who underwent disconnection surgery for medically intractable ES at the authors' institution between May 2015 and April 2021. Patients with suggested focal-onset ES based on preoperative evaluations initially underwent lobar disconnection. Patients with suggested generalized or unknown-onset ES underwent corpus callosotomy (CC). If evaluations after initial CC showed focalized or lateralized change, they were considered secondarily revealed focal-onset ES, and lobar disconnection was performed. ES outcomes were evaluated using the International League Against Epilepsy classification. ES outcomes were divided into classes 1-4 as favorable outcomes and classes 5 and 6 as unfavorable outcomes. The relationship between the favorable postoperative ES outcomes and the following preoperative factors was analyzed: sex, age at onset (< or > 1 year), duration between seizure onset and initial surgery (< or > 2 years), type of seizure at onset (ES or others), presence of other types of seizures, substrate, hypsarrhythmia, and MRI abnormalities. The period between the last surgery and ES recurrence was also analyzed. RESULTS: A total of 41 patients were included, of whom 75.6% achieved favorable ES outcomes. A longer seizure duration between seizure onset and initial surgery, presence of hypsarrhythmia, and positive MRI findings led to poorer postoperative ES outcomes (p = 0.0028, p = 0.0041, and p = 0.0241, respectively). A total of 60.9% of patients had ES recurrence during the follow-up period, and their ES recurred within 13 months after the last surgery. CONCLUSIONS: Disconnection surgery is an effective treatment option for medically intractable ES, even when the preoperative evaluation suggests a generalized or unknown onset.

Association between diffuse cerebral MRI lesions and the occurrence and intractableness of West syndrome in tuberous sclerosis complex.

OBJECTIVE: We aimed to clarify the association between magnetic resonance imaging (MRI)-lesion patterns, including cortices and white matters, and the development, occurrence, and intractableness of West syndrome in patients with tuberous sclerosis complex (TSC), using visual analysis. METHODS: We collected data for 44 patients with TSC who had undergone brain MRI and developmental evaluation after the ages of 2 and 3 years, respectively. Fluid-attenuated inversion recovery (FLAIR) and T1-weighted images were used to analyze the number of cyst-like tubers, the number of cyst-like subcortical lesions, and the presence of diffuse lesions involving the cortices and white matter. RESULTS: Developmental delays were observed in 28 patients. Nineteen patients had a history of West syndrome. Cyst-like tubers (range: 1-10), cyst-like subcortical lesions (range: 1-4), and diffuse lesions (range: 1-6 areas) were observed in 15, 9, and 14 patients, respectively. In the univariate analyses, all MRI findings were associated with development and/or history of West syndrome. However, in the multivariate analyses, only the diffuse lesion was associated with severe development (p = 0.003) and history of West syndrome (p = 0.012). In the subanalysis of patients with West syndrome, the diffuse lesions were also associated with pharmacological intractableness. Patients with diffuse lesions had a history of West syndrome with sensitivity of 68% and specificity of 96%. Patients with two or more areas of diffuse lesions had history of pharmacologically intractable West syndrome with sensitivity of 89% and specificity of 91%. CONCLUSIONS: Diffuse lesions may help to predict the poor neurological outcomes in patients with TSC.

Nitric oxide represses the proliferation of Caco-2 cells by inducing S-G2/M cell cycle arrest.

There is conflicting data regarding the ability of nitric oxide (NO) to promote or inhibit colorectal cancer cell proliferation. Furthermore, NO reacts rapidly with endogenous superoxide at a diffusion-controlled rate to give peroxynitrite (ONOO-), a strong oxidant and nitrating agent. The aim of this study was to assess the effects of exogenous NO and ONOO- on the proliferation of the colorectal cancer cell line Caco-2. NOR5 and SIN-1 were used as NO and ONOO- donors, respectively. Both NOR5 and SIN-1 inhibited the proliferation of the Caco-2 cells; however, the effect of NOR5 was slightly stronger than that of SIN-1. The results also indicated that NO plays a major role in the inhibition of SIN-1-induced proliferation of Caco-2 cells. The results of a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, cell cycle analysis, and p21 protein expression measurement further indicated that NO induced S-G2/M phase arrest, but not apoptosis, in the Caco-2 cells. The results suggest that NO, rather than ONOO-, has the potential to repress the proliferation of Caco-2 cells by inducing S-G2/M cell cycle arrest.

Hydrogen sulfide donor GYY4137 suppresses proliferation of human colorectal cancer Caco-2 cells by inducing both cell cycle arrest and cell death.

Conflicting data regarding the ability of hydrogen sulfide (H2S), which reaches high levels in the large intestine owing to biosynthesis in the intestinal cells and intestinal bacteria, to promote or inhibit colorectal cancer cell proliferation have been reported recently. In the present study, the effect of H2S on the proliferation of the human colorectal cancer cell line Caco-2 was examined by using the H2S donor GYY4137. At concentrations of 0.5 mM and 1.0 mM, GYY4137 significantly inhibited Caco-2 cell viability. Cell cycle analysis, and apoptosis and necrosis detection revealed that the anti-proliferative effect of GYY4137 was partially attributable to the induction of S-G2/M cell cycle arrest, apoptosis and necrosis. These results suggest that H2S has the potential to suppress human colorectal cancer cell proliferation by influencing both cell cycle and cell death.

The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals.

Despite evidence that tripeptide glycyl-ʟ-histidyl-ʟ-lysine (GHK) is an endogenous antioxidant, its mechanism and importance are not fully understood. In the present study, the ability of GHK to reduce levels of reactive oxygen species (ROS) in Caco-2 cells was evaluated by flow cytometry with the oxidation-sensitive fluorescent dye 2',7'-dichlorodihydrofluorescein diacetate. Further, types of ROS diminished by GHK were assessed by utilizing an electron spin resonance (ESR) spin-trapping technique. GHK reduced the tert-butyl hydroperoxide-induced increase in ROS levels in Caco-2 cells at concentrations of 10 µM or less. Experiments utilizing an ESR spin-trapping technique revealed that, among hydroxyl (·OH), superoxide (O2-·), and peroxyl (ROO·) radicals generated by respective chemical reaction systems, GHK diminished signals of both ·OH and ROO·, but not O2-·. Additionally, the GHK effect on the signal of ·OH was much stronger than those of other well-known antioxidative, endogenous peptides, carnosine and reduced glutathione. These results suggest that GHK can function as an endogenous antioxidant in living organisms, possibly by diminishing ·OH and ROO·.

Curcumin inhibits adipogenesis induced by benzyl butyl phthalate in 3T3-L1 cells.

Phthalates are a group of endocrine disrupting chemicals and may have contributed to the recent global obesity health crisis. Increased adipogenesis via the peroxisome proliferator-activated receptor γ (PPARγ)-CCAAT-enhancer binding protein α (C/EBPα) pathway could be one critical mechanism responsible for phthalate-induced weight gain. On the other hand, curcumin has been shown to inhibit adipogenesis in cells and animal models. The present study was undertaken to evaluate, for the first time, whether curcumin could reduce adipogenesis induced by benzyl butyl phthalate (BBP) via downregulation of the PPARγ-C/EBPα pathway. 3T3-L1 preadipocytes were differentiated by treating them with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of BBP, with or without curcumin. Cells that were grown in the presence of BBP alone showed a significant increase in triacylglycerol (TG) levels. In addition, the number of Oil Red O-stained cells and the mRNA expression levels of PPARγ, C/EBPα, adiponectin, and tumor necrosis factor-α (TNFα) were significantly increased. However, treatment with BBP in combination with curcumin resulted in major reductions in TG levels, the numbers of Oil Red O-stained cells, and the mRNA expression levels of the four proteins. These results suggest that curcumin might be an inhibitor of BBP-induced weight gain and inflammation via stimulation of adipocyte differentiation and TNFα generation. Curcumin may, therefore, be a potential medication for preventing the harmful effects of phthalates.

Increased subcortical oligodendroglia-like cells in pharmacoresistant focal epilepsy in children correlate with extensive epileptogenic zones.

OBJECTIVE: Cortical resections in epilepsy surgery tend to involve multiple lobes in children, compared to adults, partly due to underlying pathology. Oligodendroglia-like cells (OLCs) have been observed in surgical specimens from children with pharmacoresistant epilepsy. We hypothesize that OLCs recruit multiple-lobe epileptogenic zones in pediatric pharmacoresistant focal epilepsy. METHODS: We examined the surgical specimens from 30 children who underwent epilepsy surgery (1.8- to 16.9-years-old; mean age 9.7 years). Immunohistochemical assays of OLCs were performed using Olig2, which is a marker of OLC. OLC populations in three sites (gray matter, gray-white matter junction, and white matter) were counted. We also performed immunohistochemical staining with neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) for neuronal and astroglial markers, respectively. NeuN- and GFAP-positive cells were distinguished from OLCs. OLC results were compared with seizure types, scalp and intracranial video-electroencephalography (EEG), magnetic resonance imaging (MRI), surgical resection area, histopathologic diagnosis, and seizure outcome. RESULTS: Histopathologic diagnosis consisted of 14 cases of focal cortical dysplasia (FCD; type I; 4, type II; 9, type III; one); 6 cases of oligodendrogliosis; 6 cases of astrocytic gliosis; 2 cases of hyaline protoplasmic astrocytopathy; and 2 cases of tuberous sclerosis. Fifteen children (50%) underwent multiple-lobe resections after intracranial video-EEG. There was a positive correlation between the number of resected electrodes and the OLC population in the white matter (correlation coefficient 0.581, p = 0.001) and at the gray-white matter junction- (correlation coefficient 0.426, p = 0.027). OLC populations in both areas were increased significantly in nine children with epileptic spasms (ES) (gray-white matter junction [p = 0.021] and white matter [p = 0.025]), and nine nonfocal ictal scalp EEG findings (gray-white matter junction [p = 0.04] and white matter [p = 0.042]). The OLC population in white matter was significantly increased in children with 11 nonfocal interictal scalp EEG findings (p = 0.01), with 15 multiple-lobe resections (p = 0.028). SIGNIFICANCE: Pharmacoresistant epilepsy in children with increased OLCs presented with nonfocal epileptiform discharges on scalp EEG and ES, and they required multiple-lobe resections. We found increased populations of subcortical OLCs in the extensive epileptogenic zone.

Remote MEG dipoles in focal cortical dysplasia at bottom of sulcus.

OBJECTIVE: To investigate whether the magnetoencephalography (MEG) single moving dipole (SMD) method could delineate the epileptic zone of focal cortical dysplasia (FCD) at the bottom of sulcus (FCDB). METHODS: We retrospectively analyzed 17 children (11 male; mean age 8.8 years, range 3-17 years) with FCD type II who underwent epilepsy surgery. We compared spatial congruence between the following: (1) MEG cluster and FCDB and (2) MEG cluster and FCD at the brain surface (FCDS). We measured the volume and depth of magnetic resonance imaging (MRI)-visible lesions to investigate whether they affect spatial congruence between MEG cluster and MRI-visible lesion. RESULTS: Eight children had FCDB and the other nine children had FCDS. The volume of MRI-visible lesions for FCDB ranged from 1,632 to 4,707 mm(3) (mean ± standard deviation [SD] 3,095 ± 1,211 mm(3) ). The depth of FCDB ranged from 19 to 33 mm (mean ± SD 26 ± 4 mm). The volume of MRI-visible lesion for FCDS ranged from 2,375 to 57,331 mm(3) (15,470 ± 18,455 mm(3) ). There was a tendency for a smaller volume of MRI-visible lesion for FCDB, relative to FCDS(p = 0.079). In FCDB, six children showed clusters of MEG dipoles and two children showed scattered MEG dipoles for interictal spikes. The spatial congruence between the MEG result and FCDB was partially overlapping in four children and discordant in another four children. In FCDS, eight children had MEG cluster and one child had MEG scatter alone. The spatial congruence between MEG result and FCDS was overlapping in eight of nine children (fully two; partially six) and discordant in one of nine children. Fifteen children (88%; FCDB eight; FCDS seven) became seizure-free after resective surgery. MEG spike dipole resection ratio in the cluster ranged from 4-100% (mean 67%) in 6 FCDB and 23-99% (mean 77%) in 8 FCDS. SIGNIFICANCE: The SMD method may drift MEG spike dipoles for FCDB. Lesionectomy can control seizures for four of eight patients in FCDB despite the remote MEG dipoles. The FCDB or FCDS partially overlapped with MEG cluster may have an extending/invisible epileptogenic zone consecutive to the MRI-visible lesion.

Rapid eye movement sleep reveals epileptogenic spikes for resective surgery in children with generalized interictal discharges.

OBJECTIVE: Epilepsy surgery can be successful in children with extensive congenital or early acquired focal or hemispheric brain lesion on magnetic resonance imaging (MRI) despite generalized interictal epileptiform discharges (IEDs). The aim of this study was to assess if rapid eye movement (REM) sleep reduced generalized IEDs and revealed lateralized IEDs to identify the epileptogenic hemisphere in children with generalized IEDs and normal/subtle changes on MRI. METHODS: We studied 20 children with generalized IEDs on scalp electroencephalography (EEG) and normal/subtle changes on MRI who underwent intracranial video-EEG for epilepsy surgery. We assessed a minimum of 100 IEDs during REM, non-REM, and wakefulness, and assigned the distribution (generalized, left, or right hemisphere) to each IED. The number of lobes in the resected areas and seizure outcome were compared between 20 children with generalized IEDs and a comparison group of 28 children without generalized IEDs. RESULTS: The mean occurrence rate of generalized IEDs during REM (37%) was significantly lower than that during non-REM (67%, p < 0.001) and wakefulness (54%, p = 0.003). The number of children whose largest number of IEDs was lateralized in REM was significantly higher than that in non-REM (15 vs. 3 children, 75% vs. 15%, p < 0.001). The hemisphere with lateralized IEDs among three states corresponded with the surgical side in 16 children with generalized IEDs. Seventeen children (85%) with generalized IEDs and 27 (96%) without generalized IEDs underwent resective surgery. Multilobar resection was required for 16 children (94%) with generalized IEDs more frequently than 7 children (26%) without generalized IEDs (p < 0.001). Thirteen children (77%) with generalized IEDs and 19 (73%) without generalized IEDs were seizure-free with a mean of 3.3 years of follow-up. SIGNIFICANCE: Our study demonstrates the importance of assessing REM in children with generalized IEDs as it reveals lateralized epileptogenic spikes. Seizure freedom may be achieved with multilobar resection in these children with generalized IEDs and normal/subtle changes on MRI. Generalized IEDs in children with normal/subtle changes on MRI should not preclude surgical resection.

Hydrogen peroxide generated by xanthine/xanthine oxidase system represses the proliferation of colorectal cancer cell line Caco-2.

The twin character of reactive oxygen species is substantiated by a growing body of evidence that reactive oxygen species within cells act as inducers and accelerators of the oncogenic phenotype of cancer cells, while reactive oxygen species can also induce cancer cell death and can therefore function as anti-tumorigenic species. The aim of this study was to assess a possible influence of xanthine/xanthine oxidase on the proliferation of colorectal cancer cell line Caco-2. xanthine/xanthine oxidase (2.5 µM/0.25 mU/ml-25 µM/2.5 mU/ml) dose-dependently inhibited the proliferation of Caco-2 cells. Experiments utilizing reactive oxygen species scavengers (superoxide dismutase, catalase and mannitol) and exogenous hydrogen peroxide revealed a major role of hydrogen peroxide in the xanthine/xanthine oxidase effect. Investigations utilizing annexin V-fluorescein/PI assay using flow cytometry, and the lactate dehydrogenase extracellular release assay indicated that hydrogen peroxide induced necrosis, but not apoptosis, in Caco-2 cells. These results suggest that hydrogen peroxide generated by xanthine/xanthine oxidase has the potential to suppress colorectal cancer cell proliferation.

Asymmetrical generalized paroxysmal fast activities in children with intractable localization-related epilepsy.

BACKGROUND: Generalized paroxysmal fast activity (GPFA) consists of burst of generalized rhythmic discharges; 100-200 µV; 1-9s; 8-26 Hz; with frontal predominance; appearing during NREM sleep. GPFA was originally described as an electrographic feature of Lennox-Gastaut Syndrome (LGS). We analyzed GPFA on scalp video EEG (VEEG) in children to evaluate that GPFA presents in patients with intractable localization-related epilepsy. METHODS: We collected cases with GPFA with intractable localization-related epilepsy who underwent scalp VEEG, MRI, and magnetoencephalography (MEG) prior to intracranial video EEG (IVEEG) and surgical resection. We collected 50 epochs of GPFA per patient during the first night during scalp VEEG. We analyzed amplitude, duration and frequency of GPFA over the bilateral frontal region between surgical resection side with grid placement and non-resection side. RESULTS: We identified 14 (14%) patients with GPFA on scalp VEEG. The mean amplitude ranged from 145 to 589 µV (mean 293 µV). The mean duration ranged from 1.18 to 2.31s (mean 1.6s). The mean frequencies ranged from 9.3 to 14.7 Hz (mean 11.1 Hz). The amplitude (307 ± 156 µV) and duration (1.62 ± 0.8s) of GPFAs in all the patients over the resection side were significantly higher than those (279 ± 141 µV, 1.58 ± 0.8s) of the non-resection side (p<0.001). All nine patients who showed significant duration differences between two hemispheres (p<0.05) had longer duration of GPFA over the resection side. Eight of 12 patients who showed significant amplitude differences between two hemispheres (p<0.05) had higher amplitude of GPFA over the resection side. Four of six patients who showed significant frequency differences between two hemispheres (p<0.05) had higher frequency of GPFA over the resection side. Nine (64%) patients became seizure free after surgical resection including multilobar resections in eight patients. CONCLUSIONS: GPFA can exist in localization-related epilepsy with secondary bilateral synchrony. Although EEG shows GPFA on scalp VEEG, the precise localization of the epileptogenic zone using IVEEG could achieve the successful surgical resection.

Dynamic Change in Cells Expressing IL-1ß in Rat Hippocampus after Status Epilepticus.

BACKGROUND: The time course of cytokine dynamics after seizure remains controversial. Here we evaluated the changes in the levels and sites of interleukin (IL)-1ß expression over time in the hippocampus after seizure. METHODS: Status epilepticus (SE) was induced in adult Wistar rats by means of intraperitoneal injection of kainic acid (KA). Subsequently, the time courses of cellular localization and IL-1ß concentration in the hippocampus were evaluated by means of immunohistochemical and quantitative assays. RESULTS: On day 1 after SE, CA3 pyramidal cells showed degeneration and increased IL-1ß expression. In the chronic phase (>7 days after SE), glial fibrillary acidic protein (GFAP)-positive reactive astrocytes-appeared in CA1 and became IL-1ß immunoreactive. Their IL-1ß immunoreactivity increased in proportion to the progressive hypertrophy of astrocytes that led to gliosis. Quantitative analysis showed that hippocampal IL-1ß concentration progressively increased during the acute and chronic phases. CONCLUSION: IL-1ß affects the hippocampus after SE. In the acute phase, the main cells expressing IL-1ß were CA3 pyramidal cells. In the chronic phase, the main cells expressing IL-1ß were reactive astrocytes in CA1.

Increased population of oligodendroglia-like cells in pediatric intractable epilepsy.

Pediatric focal epilepsies often involve more extratemporal regions than adult epilepsies. This study aims to investigate the population of oligodendroglia-like cells (OLCs) in the pediatric focal epilepsy patients requiring surgery. We hypothesize that OLCs are one of the factors that extend the pediatric epileptic network in intractable epilepsy. Thirty (18 female) patients (1.8-16.9 years old with a mean of 9.7 years), who underwent resective surgery for the intractable epilepsy from 2010 to 2012 were retrospectively studied. Seizure types consisted of epileptic spasms in nine patients, partial seizures in 17 patients and partial seizure with secondary generalization in four patients. Eight autopsy cases without neurological disease served as controls. The neuropathology examination utilized the H&E/LFB stain and immunohistochemical staining for NeuN, GFAP and Olig2 as a marker of OLCs. OLCs were counted in three sites: (a) gray matter, (b) junction of gray/white matter, and (c) white matter. We also examined the correlation between the density of OLC among the three sites and the clinical features. Fifteen (50%) patients underwent multiple lobe resections, consisting of both temporal and extratemporal lobe resections in 12 patients and extratemporal lobe resections in 3 patients. The other 15 (50%) patients underwent single lobe resection including 3 (10%) patients with temporal lobectomy sparing hippocampus. Pathological diagnosis of epilepsy patients was as follows: 14 (47%) patients=focal cortical dysplasia (type I, 4; II, 9; III, 1); 6 (20%)=oligodendrogliosis; 6 (20%)=astrocytic gliosis; 2 (7%)=hyaline protoplasmic astrocytopathy and 2 (7%)=tuberous sclerosis complex. The numbers of OLCs at all three sites in epilepsy group were significantly higher than those of control group (p<0.001). In the epilepsy group, there was a significant difference among the number of OLCs at gray matter, junction of gray and white matter, and white matter (p<0.001). The number of OLCs significantly increased from gray matter and junction of gray/white matter to white matter. In the control group, there was no difference among the number of OLCs at three sites. There was no significant difference in the numbers of OLCs between focal cortical dysplasia types I and II. The significantly increased OLCs, especially in the white matter may contribute to the extensive epileptic network in children with intractable focal epilepsy.

Monochloramine suppresses the proliferation of colorectal cancer cell line Caco-2 by both apoptosis and G2/M cell cycle arrest.

The aim of this study was to assess a possible role of monochloramine (NH2 Cl), one of the reactive chlorine species, which induce oxidative stress, on the proliferation of colorectal cancer cell line Caco-2. At concentrations ranging from 10 to 200 µM, NH2 Cl (14-61% inhibition), but not hypochlorous acid, dose-dependently inhibited the cell viability of Caco-2 cells. Experiments utilizing methionine (a scavenger of NH2 Cl), taurine-chloramine and glutamine-chloramine revealed that only NH2 Cl affects the cancer cell proliferation among reactive chlorine species, with a relative specificity. Furthermore, flow-cytometry experiments showed that the anti-proliferative effect of NH2 Cl is partially attributable to both apoptosis and G2/M cell cycle arrest. These results suggest that NH2 Cl has the potential to suppress colorectal cancer cell proliferation.