Search

Aims: Although programmed cell death protein 1 (PD‐1) typically serves as a target for immunotherapies, a few recent studies have found that PD‐1 is expressed in the nervous system and that neuronal PD‐1 might play a crucial role in regulating neuronal excitability. However, whether brain‐localized PD‐1 is involved in seizures and epileptogenesis is still unknown and worthy of in‐depth exploration. Methods: The existence of PD‐1 in human neurons was confirmed by immunohistochemistry, and PD‐1 expression levels were measured by real‐time quantitative PCR (RT‐qPCR) and western blotting. Chemoconvulsants, pentylenetetrazol (PTZ) and cyclothiazide (CTZ), were applied for the establishment of in vivo (rodents) and in vitro (primary hippocampal neurons) models of seizure, respectively. SHR‐1210 (a PD‐1 monoclonal antibody) and sodium stibogluconate (SSG, a validated inhibitor of SH2‐containing protein tyrosine phosphatase‐1 [SHP‐1]) were administrated to investigate the impact of PD‐1 pathway blockade on epileptic behaviors of rodents and epileptiform discharges of neurons. A miRNA strategy was applied to determine the impact of PD‐1 knockdown on neuronal excitability. The electrical activities and sodium channel function of neurons were determined by whole‐cell patch‐clamp recordings. The interaction between PD‐1 and α‐6 subunit of human voltage‐gated sodium channel (Nav1.6) was validated by performing co‐immunostaining and co‐immunoprecipitation (co‐IP) experiments. Results: Our results reveal that PD‐1 protein and mRNA levels were upregulated in lesion cores compared with perifocal tissues of surgically resected specimens from patients with intractable epilepsy. Furthermore, we show that anti‐PD‐1 treatment has anti‐seizure effects both in vivo and in vitro. Then, we reveal that PD‐1 blockade can alter the electrophysiological properties of sodium channels. Moreover, we reveal that PD‐1 acts together with downstream SHP‐1 to regulate sodium channel function and hence neuronal excitability. Further investigation suggests that there is a direct interaction between neuronal PD‐1 and Nav1.6. Conclusion: Our study reveals that neuronal PD‐1 plays an important role in epilepsy and that anti‐PD‐1 treatment protects against seizures by suppressing sodium channel function, identifying anti‐PD‐1 treatment as a novel therapeutic strategy for epilepsy. [ABSTRACT FROM AUTHOR]

Epilepsy is a kind of neurological disorder characterized by recurrent epileptic seizures. While it is crucial to characterize pre-ictal brain electrical activities, the problem to this day still remains computationally challenging. Using brain signal acquisition and advances in deep learning technology, we aim to classify pre-ictal signals and characterize the brain waveforms of patients with epilepsy during the pre-ictal period. We develop a novel machine learning model called Pre-ictal Signal Classification (PiSC) for pre-ictal signal classification and for identifying brain waveform patterns critical for seizure onset early detection. In PiSC, a unique preprocessing procedure is developed to convert the stereo-electroencephalography (sEEG) signals to data blocks ready for pre-ictal signal classification. Also, a novel deep learning framework is developed to integrate deep neural networks and meta-learning to effectively mitigate patient-to-patient variances as well as fine-tuning a trained classification model for new patients. The unique network architecture ensures model stability and generalization in sEEG data modeling. The experimental results on a real-world patient dataset show that PiSC improved the accuracy and F1 score by 10% compared with the existing models. Two types of sEEG patterns were discovered to be associated with seizure development in nocturnal epileptic patients., (©2021 AMIA - All rights reserved.)

Background: Chondromyxoid fibromas (CMFs) are benign tumors that occur rarely in the skull base., Objective: To conduct a preliminary exploration of the diagnosis and treatment of cranial CMFs., Methods: A retrospective analysis of 19 cases of CMFs in the base of the skull between 2009 and 2014 in our hospital was conducted. The clinical manifestations, imaging characteristics, pathology, treatment strategies, and outcomes were examined., Results: The study cohort included 7 women (36.8%) and 12 men (63.2%), and symptom duration ranged from 1 mo to 5 yr. Of the 19 intracranial CMF cases examined, 15 (78.9%) conformed with the diagnostic criteria for extracranial CMF. Resection operations yielded subtotal removal of 13 tumors (68.4%) and partial removal of 6 tumors (31.6%). Postoperative pathological analysis demonstrated that the tumors were characterized by spindle-shaped or stellate cells arranged in a myxoid matrix without mitoses or permeation. Follow-up (range 2-7.3 yr; mean, 4.4 ± 1.7 yr) revealed that symptoms improved postoperatively in 15 cases (78.9%), were maintained in 2 cases (10.5%), and worsened in 2 cases (10.5%). Imaging follow-up revealed that residual tumors were stable in 18 cases (94.7%) and enlarged in 1 case (5.3%)., Conclusion: An accurate diagnosis should involve comprehensive consideration of clinical, radiological, and pathological features. The treatment strategy for CMFs consists of maximizing tumor removal while protecting adjacent key structures. Postoperative stereotactic radiotherapy is appropriate for residual tumors.