BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.
Humans ; Drug Resistant Epilepsy/metabolism* ; Neuroinflammatory Diseases/immunology* ; Animals ; Brain/pathology* ; Nerve Net/pathology*

Objective To optimize the simulation of the pathological characteristics and seizure behavior of medial temporal lobe epilepsy(MTLE),we aimed to establish a chronic epilepsy model of MTLE by unilateral,single hippocampal injection of kainic acid(KA)via stereotactic surgery,and to validate this epilepsy model in terms of behavior,electrophysiology,and pathology.Methods A total of 22 healthy C57BL/6 wild-type male mice were divided randomly into a control group(n=6)and an experimental group,which received KA injections(n=16).Both groups underwent microinjection of equal doses of saline or KA in the hippocampal CA3 area via stereotactic surgery.One week later,all mice were implanted with electrodes in the hippocampal CA3 area to facilitate electroencephalogram(EEG)recording.Seizure frequency and duration were analyzed statistically.The chronic epilepsy model was assessed in terms of behavior,electrophysiology,and pathology.Results No mice in the control group experienced seizures,while all surviving mice in the experimental group developed seizures.Adult model mice exhibited chronic spontaneous seizure behaviors,such as staring,chewing,head and facial muscle twitching,and limb spasms.Two mice died as a result of the surgery,four mice died during the acute seizure phase,and ten model mice were successfully established.EEG recordings showed epileptiform changes consistent with MTLE.Immunofluorescence staining revealed neuronal loss in the CA3 area and astrocytic changes,consistent with characteristic pathological changes of hippocampal sclerosis.Conclusions The model constructed by single unilateral intrahippocampal KA injection demonstrated several advantages such as being time-efficient,easy to operate,and reproducible.This model exhibited EEG,behavioral,and neuropathological changes similar to human MTLE,making it valuable for studying effective treatments for temporal lobe epilepsy and serving as an ideal animal model for predicting outcomes of epilepsy surgery.

Objective: To construct a scientific behavioral research of pasta matrix reaching task (PMRT) and comprehensively evaluate sensory-motor dysfunction caused by brain injury. Methods: Twenty-one SD rats were subjected to 14-days pasta matrix grasping training and then were randomly divided into model group (11 rats) and sham group (6 rats). Motor cortex ischemia was induced by injection of endothelin-1 in SD rats. The number of pasta grabed by the injured forelimb and the location in matrix were evaluated daily 7 days after surgery. The infarct volume was measured by Nissl staining at the 7 days, 14 days, and 28 days after stroke. Results: The number of pasta obtained by rats was reduced from (33.43±1.02) to (20.57±0.57) at 7 days post stroke in model group, and then increased to (26.85±0.98) at 28 days post stroke, although there was a significant difference between sham group(32.33±1.45) and ischemic group (t=3.198, P<0.05). The frequency of retrieval from each slot of the pasta matrix represented that sham group demonstrated a significant gain in performance in the antero quadrant of the matrix compared to ischemic rats by the fourth week after stroke.The stroke volume was decreased from (37.82±1.17)mm³ at 7 days post-stroke to (24.35±0.38)mm³ at 28 days post-stroke, indicating brain recovery from ischemic injury. Conclusion The pasta matrix reaching task can function as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies and focused rehabilitative training after stroke.