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Objective: To assess seizure outcomes, prognostic factors, and developmental changes in children undergoing total posterior quadrant disconnection (PQD) for drug‐resistant epilepsy (DRE). Methods: We conducted a retrospective analysis of the clinical data of children with DRE who underwent total PQD surgery. The study focused on Engel's classification for seizure outcomes, exploring correlation of preoperative data and surgical effectiveness, and predictors of seizure prognosis. It involved a comparative analysis of developmental levels pre‐ and 3 months postoperatively using Griffiths Mental Development Scales‐China (GMDS‐C), and the correlation between clinical characteristics and GMDS‐C results. Results: Out of 61 pediatric patients, 70.5% showed no seizure recurrence postoperatively. In the univariate analysis, interictal electroencephalogram (EEG), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG‐PET), and acute postoperative seizure (APOS) were significantly related to surgical prognosis. In multivariate analysis, interictal EEG and APOS were identified as predictors of seizure prognosis. Survival analysis indicated significant associations between MRI, interictal EEG, FDG‐PET, APOS and postoperative seizure occurrence. Preoperative GMDS‐C levels were significantly correlated with epilepsy duration, seizure frequency, interictal EEG, and FDG‐PET. GMDS‐C scores improved postoperatively, while developmental quotients remained stable. Significance: For patients with structural abnormalities in the entire posterior quadrant, thorough preoperative assessment and timely total PQD surgery can effectively control seizures without causing neurological development deterioration. APOS and interictal EEG abnormalities beyond the posterior quadrant are predictors for seizure prognosis but should not be deemed contraindications for surgery. Plain Language Summary: Due to lack of analysis on pediatric total PQD cases, 61 pediatric patients who underwent total PQD surgery were retrospectively enrolled. Seizure and development results were collected and analyzed as dependent variables. The study found that 70.5% of patients were seizure‐free and showed development improvement, with no deaths or severe complications reported. Prognosis predictors included APOS and interictal EEG abnormalities beyond the posterior quadrant. [ABSTRACT FROM AUTHOR]

Aims: To investigate post‐operative seizure outcomes, and predictors of surgical outcomes of the malformation of cortical development (MCD) in children with drug‐resistant epilepsy (DRE) and age‐specific characteristics. Methods: We retrospectively analyzed clinical data from 428 children with MCD‐related DRE who underwent curative surgical treatment. Statistical analyses were conducted to identify correlative characteristics, prognostic predictors, and differences among various age groups. Results: After more than 3 years of follow‐up, 81.3% of patients achieved Engel I outcomes. Prognosis was correlated with factors such as age at surgery, MRI findings, invasive EEG, pathology, acute postoperative seizures (APOS), and the number of preoperative and postoperative anti‐seizure medications (AEDs). Age at surgery and the number of preoperative AEDs (p < 0.001) were significant predictors of seizure recurrence. Distinct clinical characteristics were observed among different age groups. Conclusion: Surgery is effective in terminating MCD‐related DRE. Younger age at surgery and fewer preoperative AEDs are associated with better prognoses. Clinical characteristics vary significantly with age. [ABSTRACT FROM AUTHOR]

Hemispherotomy is an effective surgery for treating refractory epilepsy from diffuse unihemispheric lesions. To date, postsurgery neuroplastic changes supporting behavioral recovery after left or right hemispherotomy remain unclear. In the present study, we systematically investigated changes in gray matter volume (GMV) before and after surgery and further analyzed their relationships with behavioral scores in two large groups of pediatric patients with left and right hemispherotomy (29 left and 28 right). To control for the dramatic developmental effect during this stage, age‐adjusted GMV within unaffected brain regions was derived voxel by voxel using a normative modeling approach with an age‐matched reference cohort of 2115 healthy children. Widespread GMV increases in the contralateral cerebrum and ipsilateral cerebellum and GMV decreases in the contralateral cerebellum were consistently observed in both patient groups, but only the left hemispherotomy patients showed GMV decreases in the contralateral cingulate gyrus. Intriguingly, the GMV decrease in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in the right but not the left hemispherotomy patients. Importantly, the preoperative voxelwise GMV features can be used to significantly predict postoperative behavioral scores in both patient groups. These findings indicate an important role of the contralateral cerebellum in the behavioral recovery following right hemispherotomy and highlight the predictive potential of preoperative imaging features in postoperative behavioral performance. [ABSTRACT FROM AUTHOR]

Objective: To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). Methods: We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long‐term outcomes after surgical or nonsurgical (anti‐seizure medications, ASMs) treatment. Results: A total of 70 patients (49 surgical, 21 non‐surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0–4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow‐up (median 14.1 years), the rates of seizure‐freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure‐freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. Significance: In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. Plain Language Summary: We aim to summarize clinical characteristics and compare the long‐term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)‐related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant. [ABSTRACT FROM AUTHOR]

Aims: To predict the vagus nerve stimulation (VNS) efficacy for pediatric drug‐resistant epilepsy (DRE) patients, we aim to identify preimplantation biomarkers through clinical features and electroencephalogram (EEG) signals and thus establish a predictive model from a multi‐modal feature set with high prediction accuracy. Methods: Sixty‐five pediatric DRE patients implanted with VNS were included and followed up. We explored the topological network and entropy features of preimplantation EEG signals to identify the biomarkers for VNS efficacy. A Support Vector Machine (SVM) integrated these biomarkers to distinguish the efficacy groups. Results: The proportion of VNS responders was 58.5% (38/65) at the last follow‐up. In the analysis of parieto‐occipital α band activity, higher synchronization level and nodal efficiency were found in responders. The central‐frontal θ band activity showed significantly lower entropy in responders. The prediction model reached an accuracy of 81.5%, a precision of 80.1%, and an AUC (area under the receiver operating characteristic curve) of 0.838. Conclusion: Our results revealed that, compared to nonresponders, VNS responders had a more efficient α band brain network, especially in the parieto‐occipital region, and less spectral complexity of θ brain activities in the central‐frontal region. We established a predictive model integrating both preimplantation clinical and EEG features and exhibited great potential for discriminating the VNS responders. This study contributed to the understanding of the VNS mechanism and improved the performance of the current predictive model. [ABSTRACT FROM AUTHOR]

Purpose: Neuropilin-1 (NRP-1) is a multifunctional protein involved in a variety of biological processes such as angiogenesis, tumorigenesis and immunomodulation. It was usually overexpressed in many cancer cell lines and correlated with poor prognosis of breast cancer. Positron emission tomography (PET) is an advanced imaging technique for detecting the function and metabolism of tumor-associated molecules in real time, dynamically, quantitatively and noninvasively. To improve the level of early diagnosis and evaluate the prognosis of breast cancer, an NRP-1 targeting peptide-based tracer [68 Ga]Ga-NOTA-PEG4-CK2 was designed to sensitively and specifically detect the NRP-1 expression in vivo via PET imaging. Methods: In silico modeling and microscale thermophoresis (MST) assay were carried out to design the NRP-1 targeting peptide NOTA-PEG4-CK2, and it was further radiolabeled with 68 Ga to prepare the tracer [68 Ga]Ga-NOTA-PEG4-CK2. The radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), lipid-water partition coefficient (Log P) and stability of [68 Ga]Ga-NOTA-PEG4-CK2 were assessed. The targeting specificity of the tracer for NRP-1 was investigated by in vitro cellular uptake assay and in vivo PET imaging as well as blocking studies. The sensitivity of the tracer in monitoring the dynamic changes of NRP-1 expression induced by chemical drug was also investigated in vitro and in vivo. Ex vivo biodistribution, autoradiography, western blot, and immunofluorescence staining were also performed to study the specificity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1. Results: [68 Ga]Ga-NOTA-PEG4-CK2 was designed and synthesized with high RCY (> 98%), high stability (RCP > 95%) and high affinity to NRP-1 (KD = 25.39 ± 1.65 nM). In vitro cellular uptake assay showed that the tracer [68 Ga]Ga-NOTA-PEG4-CK2 can specifically bind to NRP-1 positive cancer cells MDA-MB-231 (1.04 ± 0.04% at 2 h) rather than NRP-1 negative cancer cells NCI-H1299 (0.43 ± 0.05%). In vivo PET imaging showed the maximum tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 in MDA-MB-231 xenografts (4.16 ± 0.67%ID/mL) was significantly higher than that in NCI-H1299 xenografts (1.03 ± 0.19%ID/mL) at 10 min post injection, and the former exhibited higher tumor-to-muscle uptake ratio (5.22 ± 0.18) than the latter (1.07 ± 0.27) at 60 min post injection. MDA-MB-231 xenografts pretreated with nonradioactive precursor NOTA-PEG4-CK2 showed little tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 (1.67 ± 0.38%ID/mL at 10 min post injection). Both cellular uptake assay and PET imaging revealed that NRP-1 expression in breast cancer MDA-MB-231 could be effectively suppressed by SB-203580 treatment and can be sensitively detected by [68 Ga]Ga-NOTA-PEG4-CK2. Ex vivo analysis also proved the high specificity and sensitivity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1 expression in MDA-MB-231 xenografts. Conclusion: A promising NRP-1 targeting PET tracer [68 Ga]Ga-NOTA-PEG4-CK2 was successfully prepared. It showed remarkable specificity and sensitivity in monitoring the dynamic changes of NRP-1 expression. Hence, it could provide valuable information for early diagnosis of NRP-1 relevant cancers and evaluating the prognosis of cancer patients. A novel promising NRP-1 targeting PET tracer [68 Ga]Ga-NOTA-PEG4-CK2 was developed based on a series of in vitro and in vivo investigations. The tracer showed remarkable specificity and sensitivity in detecting the expression of NRP-1. It could be applied for noninvasively and dynamically monitoring the NRP-1 expression in tumors and predicting the prognosis of breast cancer. [ABSTRACT FROM AUTHOR]