Predictors of seizure outcomes in stereo-electroencephalography-guided radio-frequency thermocoagulation for MRI-negative epilepsy.

Background: One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery. Objective: This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy. Design: This was a single-center retrospective cohort study. Methods: We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis. Results: With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387). Conclusion: Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

Deep brain stimulation suppresses epileptic seizures in rats via inhibition of adenosine kinase and activation of adenosine A1 receptors.

AIMS: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus, is an effective therapy for patients with drug-resistant epilepsy, yet, its mechanism of action remains elusive. Adenosine kinase (ADK), a key negative regulator of adenosine, is a potential modulator of epileptogenesis. DBS has been shown to increase adenosine levels, which may suppress seizures via A1 receptors (A1 Rs). We investigated whether DBS could halt disease progression and the potential involvement of adenosine mechanisms. METHODS: Control group, SE (status epilepticus) group, SE-DBS group, and SE-sham-DBS group were included in this study. One week after a pilocarpine-induced status epilepticus, rats in the SE-DBS group were treated with DBS for 4 weeks. The rats were monitored by video-EEG. ADK and A1 Rs were tested with histochemistry and western blot, respectively. RESULTS: Compared with the SE group and SE-sham-DBS group, DBS could reduce the frequency of spontaneous recurrent seizures (SRS) and the number of interictal epileptic discharges. The DPCPX, an A1 R antagonist, reversed the effect of DBS on interictal epileptic discharges. In addition, DBS inhibited the overexpression of ADK and the downregulation of A1 Rs. CONCLUSION: The findings indicate that DBS can reduce SRS in epileptic rats via inhibition of ADK and activation of A1 Rs. A1 Rs might be a potential target of DBS for the treatment of epilepsy.

Long-term ANT-DBS effects in pilocarpine-induced epileptic rats: A combined 9.4T MRI and histological study.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures in animals and humans however, its therapeutic mechanisms remain elusive. This study aimed to combine 9.4T multimodal magnetic resonance imaging (MRI) with histology to investigate the longitudinal effects of long-term ANT-DBS in pilocarpine-induced epileptic rats. Status epilepsy (SE) was induced by LiCl-pilocarpine injection in 11 adult male Sprague-Dawley rats. Four weeks after SE, chronic epileptic rats underwent either ANT-DBS (n = 6) or sham-DBS (n = 5) surgery. Electroencephalography (EEG) and spontaneous recurrent seizures (SRS) were recorded for 1 week. The T2-weighted image and images from resting-state functional MRI (rs-fMRI) were acquired at three states: before SE, at 4 weeks post-SE, and at 5 weeks post-DBS. Volumes of the hippocampal subregions and hippocampal-related functional connectivity (FC) were compared longitudinally. Finally, antibodies against neuronal nuclei (NeuN) and glial fibrillary acidic proteins were used to evaluate neuronal loss and astrogliosis in the hippocampus. Long-term ANT-DBS significantly reduced seizure generalization in pilocarpine-induced epileptic rats. By analyzing the gray matter volume using T2-weighted images, long-term ANT-DBS displayed morphometric restoration of the hippocampal subregions. Neuronal protection of the hippocampal subregions and inhibition of astrogliosis in the hippocampal subregions were observed in the ANT-DBS group. ANT-DBS caused reversible regulation of FC in the insula-hippocampus and subthalamic nucleus-hippocampus. Long-term ANT-DBS provides comprehensive protection of hippocampal histology, hippocampal morphometrics, and hippocampal-related functional networks.

Epilepsy and Autism Spectrum Disorder (ASD): The Underlying Mechanisms and Therapy Targets Related to Adenosine.

Epilepsy and autism spectrum disorder (ASD) are highly mutually comorbid, suggesting potential overlaps in genetic etiology, pathophysiology, and neurodevelopmental abnormalities. Adenosine, an endogenous anticonvulsant and neuroprotective neuromodulator of the brain, has been proved to affect the process of epilepsy and ASD. On the one hand, adenosine plays a crucial role in preventing the progression and development of epilepsy through adenosine receptordependent and -independent ways. On the other hand, adenosine signaling can not only regulate core symptoms but also improve comorbid disorders in ASD. Given the important role of adenosine in epilepsy and ASD, therapeutic strategies related to adenosine, including the ketogenic diet, neuromodulation therapy, and adenosine augmentation therapy, have been suggested for the arrangement of epilepsy and ASD. There are several proposals in this review. Firstly, it is necessary to further discuss the relationship between both diseases based on the comorbid symptoms and mechanisms of epilepsy and ASD. Secondly, it is important to explore the role of adenosine involved in epilepsy and ASD. Lastly, potential therapeutic value and clinical approaches of adenosine-related therapies in treating epilepsy and ASD need to be emphasized.

Correlation Between Ictal Signs and Anatomical Subgroups in Temporal Lobe Seizures: A Stereoelectroencephalography Study.

Objective: Ictal semiology is a fundamental part of the presurgical evaluation of patients with temporal lobe epilepsy. We aimed to identify different anatomical and semiologic subgroups in temporal lobe seizures, and investigate the correlation between them. Methods: We enrolled 93 patients for whom stereoelectroencephalography exploration indicated that the seizure-onset zone was within the temporal lobe. Ictal signs and concomitant stereoelectroencephalography changes were carefully reviewed and quantified, and then cluster analysis and the Kendall correlation test were used to associate ictal signs with the temporal structures of patients. Results: Clustering analysis identified two main groups of temporal structures. Group 1 consisted of the medial temporal lobe structures and the temporal pole, which were divided into two subgroups. Group 1A included the hippocampal head, hippocampal body, and amygdala, and this subgroup correlated significantly with oroalimentary automatisms, feeling of fear, and epigastric auras. Group 1B included the hippocampal tail, temporal pole, and parahippocampal gyrus, and this subgroup correlated significantly with manual and oroalimentary automatisms. Group 2 consisted of the cortical structures of the temporal lobe and was also divided into two subgroups. Group 2A included the superior and middle temporal gyrus, correlated significantly with bilateral rictus/facial contraction, generalized tonic-clonic seizure, and manual automatisms. Group 2B included Heschl's gyrus, the inferior temporal gyrus, and the fusiform gyrus, and this subgroup correlated significantly with auditory auras, focal hypokinetics, unilateral upper and lower limbs tonic posture/clonic signs, head/eye deviation, unilateral versive signs, and generalized tonic-clonic seizure. Significance: The temporal structures can be categorized according to the level at which each structure participates in seizures, and different anatomical subgroups can be correlated with different ictal signs. Identifying specific semiologic features can help us localize the epileptogenic zone and thus develop stereoelectroencephalography electrode implantation and surgical resection protocols for patients with temporal lobe epilepsy.