Long-term Efficacy of Bilateral Globus Pallidus Stimulation in the Treatment of Meige Syndrome.

OBJECTIVE: This study aimed to investigate the long-term efficacy and prognosis of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in patients with benign essential blepharospasm (BEB) and complete Meige syndrome, and to search for the best therapeutic subregion within the GPi. MATERIALS AND METHODS: Data were collected for 36 patients with Meige syndrome who underwent bilateral GPi-DBS surgery at our hospital between March 2014 and February 2022. Using the Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS)-Movement (BFMDRS-M) and BFMDRS-Disability (BFMDRS-D), the severity of the symptoms of patients with complete Meige syndrome was evaluated before surgery and at specific time points after surgery. Patients with BEB were clinically evaluated for the severity of blepharospasm using BFMDRS-M, the Blepharospasm Disability Index (BDI), and Jankovic Rating Scale (JRS). Three-dimensional reconstruction of the GPi-electrode was performed in some patients using the lead-DBS software, and the correlation between GPi subregion volume of tissue activated (VTA) and symptom improvement was analyzed in patients six months after surgery. The follow-up duration ranged from six to 99 months. RESULTS: Compared with preoperative scores, the results of all patients at six months after surgery and final follow-up showed a significant decrease (p < 0.05) in the mean BFMDRS-M score. Among them, the average BFMDRS-M improvement rates in patients with BEB at six months after surgery and final follow-up were 60.3% and 69.7%, respectively, whereas those in patients with complete Meige syndrome were 54.5% and 58.3%, respectively. The average JRS and BDI scores of patients with BEB also decreased significantly (p < 0.05) at six months after surgery and at the final follow-up (JRS improvement: 38.6% and 49.1%, respectively; BDI improvement: 42.6% and 57.4%, respectively). We were unable to identify significantly correlated prognostic factors. There was a significant correlation between GPi occipital VTA and symptom improvement in patients at six months after surgery (r = 0.34, p = 0.025). CONCLUSIONS: Our study suggests that bilateral GPi-DBS is an effective treatment for Meige syndrome, with no serious postoperative complications. The VTA in the GPi subregion may be related to the movement score improvement. In addition, further research is needed to predict patients with poor surgical outcomes.

Functional Hydrogel Co-Remolding Migration and Differentiation Microenvironment for Severe Spinal Cord Injury Repair.

Spinal cord injury (SCI) activates nestin+ neural stem cells (NSCs), which can be regarded as potential seed cells for neuronal regeneration. However, the lesion microenvironment seriously hinders the migration of the nestin+ cells to the lesion epicenter and their differentiation into neurons to rebuild neural circuits. In this study, a photosensitive hydrogel scaffold is prepared as drug delivery carrier. Genetically engineered SDF1α and NT3 are designed and the scaffold is binary modified to reshape the lesion microenvironment. The binary modified scaffold can effectively induce the migration and neuronal differentiation of nestin+ NSCs in vitro. When implanted into a rat complete SCI model, many of the SCI-activated nestin+ cells migrate into the lesion site and give rise to neurons in short-term. Meanwhile, long-term repair results also show that implantation of the binary modified scaffold can effectively promote the maturation, functionalization and synaptic network reconstruction of neurons in the lesion site. In addition, animals treated with binary scaffold also showed better improvement in motor functions. The therapeutic strategy based on remolding the migration and neuronal differentiation lesion microenvironment provides a new insight into SCI repair by targeting activated nestin+ cells, which exhibits excellent clinical transformation prospects.

Reduction of SIRT1-Mediated Epigenetic Upregulation of Nav1.7 Contributes to Oxaliplatin-Induced Neuropathic Pain.

BACKGROUND: Clinically, neuropathic pain is a severe side effect of oxaliplatin chemotherapy, which usually leads to dose reduction or cessation of treatment. Due to the unawareness of detailed mechanisms of oxaliplatin-induced neuropathic pain, it is difficult to develop an effective therapy and limits its clinical use. OBJECTIVES: The aim of the present study was to identify the role of sirtuin 1 (SIRT1) reduction in epigenetic regulation of the expression of voltage-gated sodium channels 1.7 (Nav1.7) in the dorsal root ganglion (DRG) during oxaliplatin-induced neuropathic pain. STUDY DESIGN: Controlled animal study. SETTING: University laboratory. METHODS: The von Frey test was performed to evaluate pain behavior in rats. Real-time quantitative polymerase chain reaction, western blotting, electrophysiological recording, chromatin immunoprecipitation, and small interfering RNA (siRNA) were used to illustrate the mechanisms. RESULTS: In the present study, we found that both the activity and expression of SIRT1 were significantly decreased in rat DRG following oxaliplatin treatment. The activator of SIRT1, resveratrol, not only increased the activity and expression of SIRT1, but also attenuated the mechanical allodynia following oxaliplatin treatment. In addition, local knockdown of SIRT1 by intrathecal injection of SIRT1 siRNA caused mechanical allodynia in naive rats. Besides, oxaliplatin treatment enhanced the action potential firing frequency of DRG neurons and the expression of Nav1.7 in DRG and activation of SIRT1 by resveratrol reversed this effect. Furthermore, blocking Nav1.7 by ProTx II (a selective Nav1.7 channel blocker) reversed oxaliplatin-induced mechanical allodynia. In addition, histone H3 hyperacetylation at the Nav1.7 promoter in DRG of rats following oxaliplatin treatment was significantly suppressed by activation of SIRT1 with resveratrol. Moreover, both the expression of Nav1.7 and histone H3 acetylation at the Nav1.7 promoter were upregulated in the DRG by local knockdown of SIRT1 with SIRT1 siRNA in naive rats. LIMITATIONS: More underlying mechanism(s) of SIRT1 reduction after oxaliplatin treatment needs to be explored in future research. CONCLUSIONS: These findings suggest that reduction of SIRT1-mediated epigenetic upregulation of Nav1.7 in the DRG contributes to the development of oxaliplatin-induced neuropathic pain in rats. The intrathecal drug delivery treatment of activating SIRT1 might be a novel therapeutic option for oxaliplatin-induced neuropathic pain.

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys.

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

Predictors of seizure outcomes in patients with diffuse low-grade glioma-related epilepsy after complete glioma removal.

AIMS: We aimed to identify predictors of postoperative seizures in patients with diffuse low-grade glioma (DLGG)-related epilepsy after complete tumor resection in this study. METHODS: We retrospectively collected data from individuals with DLGG-related epilepsy whose tumors were completely resected at Xiangya Hospital, Central South University between January 2014 and January 2020. The predictors of seizure outcomes were assessed by employing univariate analysis and a multivariate logistic regression model in a backward binary logistic regression model. RESULTS: Among the 118 cases that met the inclusion criteria, 83.05% were seizure-free following an average follow-up of 4.27 ± 1.65 years, all of whom were classified as International League Against Epilepsy class I outcome. Univariate and multivariate analyses indicated that seizure duration of >6 years (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.76-24.98; p = 0.005) and first clinical symptoms other than seizures (OR, 4.51; 95% CI, 1.43-14.23; p = 1.010) were both independent predictors of unfavorable seizure outcomes. CONCLUSION: Our results imply that satisfactory seizure outcomes can be achieved in most patients with DLGG-related epilepsy after complete tumor resection. Patients with seizure duration of >6 years or first clinical symptoms other than seizures were more likely to experience postoperative seizure recurrence.

Resective surgery for patients with frontal lobe diffuse low-grade glioma-related epilepsy: predictors of seizure outcomes.

Background: Diffuse low-grade gliomas (DLGGs) are prone to invade the frontal lobes, with seizures being the most common symptom. However, limited attention has been paid to surgical outcomes and their predictors in patients with frontal DLGG-related epilepsy. Objective: This study aimed to analyze predictors of postoperative seizure outcomes in patients with frontal DLGG-related epilepsy. Design: This is a single-center retrospective study. Methods: This study retrospectively collected data of 115 patients with frontal DLGG-related epilepsy who underwent resective surgery between January 2014 and January 2021. Patients were categorized into favorable and unfavorable seizure outcome groups based on the International League Against Epilepsy (ILAE) classification. Univariate and multivariate analyses were used to identify potential predictors of seizure outcomes. Results: The mean follow-up was 4.11 ± 2.06 years, and 77.4% (89 of 115) of patients were seizure-free. Permanent neurological deficits were observed in 7.0% (8 of 115) of patients. Univariate and multivariate analyses revealed that total tumor removal [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.12-0.82; p = 0.018] and older age at seizure onset (OR, 0.96; 95% CI, 0.93-0.99; p = 0.042) were independent predictors of favorable seizure outcomes. Conclusion: Surgical resection is an effective treatment for frontal DLGG-related epilepsy. Favorable seizure outcomes are more likely to be achieved in patients with complete tumor removal and those with older age at seizure onset.

Telemedicine for Preventing and Treating Pressure Injury After Spinal Cord Injury: Systematic Review and Meta-analysis.

BACKGROUND: Pressure injury is a common complication after a spinal cord injury. Long-term multidisciplinary follow-up is difficult after such patients have been discharged. Telemedicine promises to provide convenient and effective support for the prevention and treatment of pressure injury, but previous attempts to demonstrate that have produced inconsistent results. OBJECTIVE: The aim of this study is to evaluate the effectiveness of telemedicine in preventing and treating pressure injury among community-dwelling patients with spinal cord injury, and determine which telemedicine form is more effective. METHODS: This systematic review was performed according to the PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Network Meta-Analysis) standards. Ten databases were searched to identify randomized controlled trials and quasi-experimental studies related to the effectiveness of telemedicine intervention in patients with spinal cord injury. Two researchers worked independently and blindly selected studies, extracted data, and assessed the risk of bias. The results were described as relative risk (RR) and weighted mean difference and 95% CI. RESULTS: The 35 studies comprised 25 randomized controlled trials and 10 quasi-experimental studies involving 3131 patients. The results showed that telemedicine can significantly (P<.05) reduce the incidence of pressure injury (RR 0.24, 95% CI 0.14-0.41; P<.05; I2=0%), promote faster healing (RR 0.73, 95% CI 0.62-0.85; P<.05; I2=0%), and yield lower scores on the pressure ulcer scale of healing (weighted mean difference=-1.98, 95% CI -3.51 to -0.46; P<.05; I2=0%). Cumulative ranking estimates showed that combining telemedicine with conventional intervention (93.5%) was the most effective approach. CONCLUSIONS: Telemedicine is a feasible way to prevent pressure injury among patients with spinal cord injuries. It can decrease the incidence and severity of pressure injury and accelerate patients' healing without imposing economic burden. It is best used in tandem with other, more conventional interventions. Due to the limited quality and quantity of included studies, large-scale and well-designed randomized controlled trials are warranted.

Mental Health Effects of Entrepreneurial College Students from Different Backgrounds: The Mediating Role of Social Equity.

In this study, the impact of entrepreneurial college students from different backgrounds on mental health which is primarily based on the mediating role of social justice is studied. For this purpose, we have selected those start-up students who graduated from a university for one to two years as the research object, and 1890 questionnaires were distributed. The subjective family background, objective family background, social equity perception, anxiety, and depression of entrepreneurial college students were investigated, and the results were analyzed. The level of social equity and mental health of start-up college students with better birth was significantly higher than that of start-up college students with lower birth. Background, social equity, and positive emotions were significantly positively correlated, which was significantly negatively correlated with negative emotions, depression, and anxiety; Social equity played a partial mediating role in the relationship between birth and mental health indicators. Social equity helped to maintain the mental health of entrepreneurial college students from different backgrounds. This was of great significance to the entrepreneurial college students who come from a lower background.

Lesionectomy for cerebral sparganosis and concomitant epilepsy: A case series of 15 patients.

OBJECTIVE: To report the clinical characteristics and surgical outcomes of patients with cerebral sparganosis and concomitant epilepsy. METHODS: We retrospectively collected the clinical data of all patients with cerebral sparganosis and concomitant epilepsy who underwent lesionectomy as treatment at Xiangya Hospital, Central South University between January 2015 and August 2019. Seizure outcomes were evaluated according to the International League Against Epilepsy (ILAE) classification. ILAE classes 1 and 2 were defined as favorable seizure outcomes, whereas ILAE classes 3-6 were defined as unfavorable seizure outcomes. RESULTS: Fifteen patients with cerebral sparganosis and concomitant epilepsy who underwent lesionectomy as treatment met the inclusion criteria. Live worms were surgical removed in 80 % of patients. With a mean follow-up of 2.4 ± 1.1 years, 66.7 % of patients demonstrated favorable seizure outcomes, with improvement of symptoms other than seizures. Longer seizure duration associated with unfavorable seizure outcomes. CONCLUSIONS: Lesionectomy is an effective treatment for patients with cerebral sparganosis and concomitant epilepsy. Early surgical treatment may offer more benefits to such patients.

Systematic analysis of JmjC gene family and stress--response expression of KDM5 subfamily genes in Brassica napus.

BACKGROUND: Jumonji C (JmjC) proteins exert critical roles in plant development and stress response through the removal of lysine methylation from histones. Brassica napus, which originated from spontaneous hybridization by Brassica rapa and Brassica oleracea, is the most important oilseed crop after soybean. In JmjC proteins of Brassica species, the structure and function and its relationship with the parents and model plant Arabidopsis thaliana remain uncharacterized. Systematic identification and analysis for JmjC family in Brassica crops can facilitate the future functional characterization and oilseed crops improvement. METHODS: Basing on the conserved JmjC domain, JmjC homologs from the three Brassica species, B. rapa (AA), B. oleracea (CC) and B. napus, were identified from the Brassica database. Some methods, such as phylogenic analysis, chromosomal mapping, HMMER searching, gene structure display and Logos analysis, were used to characterize relationships of the JmjC homologs. Synonymous and nonsynonymous nucleotide substitutions were used to infer the information of gene duplication among homologs. Then, the expression levels of BnKDM5 subfamily genes were checked under abiotic stress by qRT-PCR. RESULTS: Sixty-five JmjC genes were identified from B. napus genome, 29 from B. rapa, and 23 from B. oleracea. These genes were grouped into seven clades based on the phylogenetic analysis, and their catalytic activities of demethylation were predicted. The average retention rate of B. napus JmjC genes (B. napus JmjC gene from B. rapa (93.1%) and B. oleracea (82.6%)) exceeded whole genome level. JmjC sequences demonstrated high conservation in domain origination, chromosomal location, intron/exon number and catalytic sites. The gene duplication events were confirmed among the homologs. Many of the BrKDM5 subfamily genes showed higher expression under drought and NaCl treatments, but only a few genes were involved in high temperature stress. CONCLUSIONS: This study provides the first genome-wide characterization of JmjC genes in Brassica species. The BnJmjC exhibits higher conservation during the formation process of allotetraploid than the average retention rates of the whole B. napus genome. Furthermore, expression profiles of many genes indicated that BnKDM5 subfamily genes are involved in stress response to salt, drought and high temperature.

Dual-Cues Laden Scaffold Facilitates Neurovascular Regeneration and Motor Functional Recovery After Complete Spinal Cord Injury.

Complete transection spinal cord injury (SCI) severely disrupts the integrity of both neural circuits and the microvasculature system. Hence, fabricating a functional bio-scaffold that could coordinate axonal regeneration and vascular reconstruction in the lesion area may emerge as a new paradigm for complete SCI repair. In this study, a photosensitive hydrogel scaffold loaded with collagen-binding stromal cell-derived factor-1a and Taxol liposomes is capable of inducing migration of endothelial cells and promoting neurite outgrowth of neurons in vitro. In addition, when implanted into a rat T8 complete transection SCI model, the above dual-cues laden scaffold exhibits a synergistic effect on facilitating axon and vessel regeneration in the lesion area within 10 days after injury. Moreover, long-term therapeutic effects are also observed after dual-cues laden scaffold implantation, including revascularization, descending and propriospinal axonal regeneration, fibrotic scar reduction, electrophysiological recovery, and motor function improvement. In summary, the dual-cues laden scaffold has good clinical application potential for patients with severe SCI.

The Role of Hippocampal Neurogenesis in ANT-DBS for LiCl-Pilocarpine-Induced Epileptic Rats.

PURPOSE: Abnormal neurogenesis in the hippocampus after status epilepticus (SE) has been suggested as a key pathogeny of temporal lobe epilepsy. This study aimed to investigate the effect of deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) on hippocampal neurogenesis in LiCl-pilocarpine-induced epileptic rats and to analyze its relationship with postoperative spontaneous recurrent seizures (SRS) and anxiety. METHOD: SE was induced by a systemic LiCl-pilocarpine injection in adult male rats. Rats in the DBS group underwent ANT-DBS immediately after successful SE induction. SRS was only recorded during the chronic stage. An elevated plus maze was used to evaluate the level of anxiety in rats 7, 28, and 60 days after SE onset. After the elevated plus-maze experiment, rats were sacrificed under anesthesia in order to evaluate hippocampal neurogenesis. Doublecortin (DCX) was used as a marker for neurogenesis. RESULTS: During the chronic stage, SRS in rats in the DBS group were significantly decreased. The level of anxiety was increased significantly in rats in the DBS group 28 days after SE, while no significant differences in anxiety levels were found 7 and 60 days after SE. The number of DCX-positive cells in the hippocampus was significantly increased 7 days after SE and was significantly decreased 60 days after SE in all rats in which SE was induced. However, the number of DCX-positive cells in the DBS group was significantly lower than that in the other groups 28 days after SE. CONCLUSIONS: ANT-DBS may suppress SRS and increase the postoperative anxiety of epileptic rats by influencing hippocampal neurogenesis.

Side of Lesions Predicts Surgical Outcomes in Patients With Drug-Resistant Temporal Lobe Epilepsy Secondary to Focal Cortical Dysplasia Type IIIa.

Objective: This study aims to evaluate the surgical outcomes and analyze the predictors of surgical outcomes in patients undergoing anterior temporal lobectomy (ATL) for drug-resistant temporal lobe epilepsy (TLE) secondary to focal cortical dysplasia (FCD) type IIIa. Methods: Data on patients with drug-resistant TLE secondary to FCD type IIIa who had undergone ATL at Xiangya Hospital, Central South University from January 2014 to April 2018, were collected retrospectively. International League Against Epilepsy (ILAE) classification was used to evaluate postoperative seizure outcomes. Predictors of surgical outcomes were identified by using univariate and multivariate analyses. Results: A total of 43 patients with drug-resistant TLE secondary to FCD type IIIa who had undergone ATL were included in this study. Twenty patients had right ATL, and 23 patients had left ATL. With a follow-up of 2-6 years, 76.7% (33 of 43) of patients were seizure-free. Univariate and multivariate analysis results indicated that lesions on the right side independently predict postoperative seizure freedom (OR, 0.08; 95% CI, 0.01-0.72; P = 0.024). Conclusion: ATL is an effective therapy for patients with drug-resistant TLE secondary to FCD type IIIa. Patients with lesions on the right side are more likely to achieve postoperative seizure freedom.

Prognostic factors of postoperative seizure outcomes in older patients with temporal lobe epilepsy.

OBJECTIVE: The authors of this study aimed to investigate surgical outcomes and prognostic factors in older patients with drug-resistant temporal lobe epilepsy (TLE) who had undergone resective surgery. METHODS: Data on patients older than 45 years of age with drug-resistant TLE who had undergone resective surgery at Sanbo Brain Hospital, Capital Medical University, between January 2009 and August 2017 were retrospectively collected. Postoperative seizure outcomes were evaluated according to the International League Against Epilepsy (ILAE) classification. Patients belonging to ILAE classes 1 and 2 were classified as having a favorable outcome, whereas patients belonging to ILAE classes 3-6 were classified as having an unfavorable outcome. Univariate analysis and multivariate logistic regression analysis were used to identify the potential predictors of seizure outcomes. RESULTS: A total of 45 patients older than 45 years of age who had undergone resective epilepsy surgery for TLE were included in the present study. Eight (17.8%) of 45 patients had preoperative comorbidity in addition to seizures. The average age at the time of surgery was 51.76 years, and the average duration of epilepsy at the time surgery was 18.01 years. After an average follow-up period of 4.53 ± 2.82 years (range 2-10 years), 73.3% (33/45) of patients were seizure free. Surgical complications were observed in 13.3% of patients. Univariate and multivariate analyses revealed that an MRI-negative finding is the only independent predictor of unfavorable seizure outcomes (OR 0.06, 95% CI 0.01-0.67, p = 0.023). CONCLUSIONS: Resective surgery is a safe and effective treatment for older patients with drug-resistant TLE. An MRI-negative finding independently predicts unfavorable seizure outcomes.

The role of adenosine A1 receptor agonist in adenosine augmentation therapy for patients with refractory epilepsy in Sturge-Weber syndrome: An in vitro electrophysiological study.

PURPOSES: This study was to further explore the adenosine dysfunction in refractory epilepsy in Sturge-Weber Syndrome (SWS), to evaluate the neuronal-level effect of the A1 receptor (A1R) agonist on both excitatory pyramidal neurons and inhibitory interneurons, to discuss the possibility of adenosine augmentation therapy (AAT) using A1R agonist for treating refractory epilepsy in SWS. MATERIALS AND METHODS: The intrinsic excitatory properties of pyramidal cells (PCs) and fast-spiking (FS) interneurons from human brain tissues with SWS cases and malformations of cortical development (MCD) cases were compared using electrophysiology. With application of either A1R agonist or antagonist, the neuronal-level effect of A1R agonist was evaluated in vitro in PCs and FS interneurons from SWS cases and MCD cases. RESULTS: No significant difference of passive excitatory properties of PCs and FS interneurons was found between SWS cases and MCD cases. In terms of the neuronal-level effect of A1R agonist, with 22.88 ±â€¯1.12% percentage of decreased frequency, FS interneurons showed relatively highest sensitivity of A1R agonist application, compared with PCs from SWS cases and FS interneurons and PCs from MCD cases. CONCLUSION: Our results supported the potential of AATs using A1R agonist to be a novel therapy for reducing life burden from patients with refractory epilepsy in SWS, with application to epileptic generation region but not propagation region.

Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis.

Rasmussen encephalitis (RE) is a severe pediatric inflammatory brain disease characterized by unilateral inflammation and atrophy of the cerebral cortex, drug-resistant focal epilepsy and progressive neurological and cognitive deterioration. The etiology and pathogenesis of RE remain unclear. Our previous results demonstrated that the adenosine A1 receptor (A1R) and the major adenosine-removing enzyme adenosine kinase play an important role in the etiology of RE. Because the downstream pathways of inhibitory A1R signaling are modulated by stimulatory A2AR signaling, which by itself controls neuro-inflammation, glial activation and glial glutamate homeostasis through interaction with glutamate transporter GLT-1, we hypothesized that maladaptive changes in adenosine A2A receptor (A2AR) expression are associated with RE. We used immunohistochemistry and Western blot analysis to examine the expression of A2ARs, glutamate transporter-I (GLT-1) and the apoptotic marker Bcl-2 in surgically resected cortical specimens from RE patients (n = 18) in comparison with control cortical tissue. In lesions of the RE specimen we found upregulation of A2ARs, downregulation of GLT-1 and increased apoptosis of both neurons and astroglia. Double staining revealed colocalization of A2ARs and Bcl-2 in RE lesions. These results suggest that maladaptive changes in A2AR expression are associated with a decrease in GLT-I expression as a possible precipitator for apoptotic cell loss in RE. Because A2AR antagonists are already under clinical evaluation for Parkinson's disease, the A2AR might likewise be a tractable target for the treatment of RE.

The impact of MEG results on surgical outcomes in patients with drug-resistant epilepsy associated with focal encephalomalacia: a single-center experience.

PURPOSE: To analyze the impact of magnetoencephalography (MEG) results on surgical outcomes in patients with drug-resistant epilepsy secondary to encephalomalacia. METHODS: We retrospectively reviewed 121 patients with drug-resistant epilepsy associated with encephalomalacia who underwent MEG followed by resection surgery. Patients were subdivided into concordant MEG group and dis-concordant MEG group for analysis based on whether the MEG results were in concordance with epileptogenic zones or not. RESULTS: 121 patients were included in the present study. The MEG spike sources of 73 (60.33%) patients were in concordance with epileptogenic zones while the MEG spike sources of the other 48 (39.67%) were in dis-concordance with epileptogenic zones. Favorable seizure outcomes were achieved in 79.45% (58 of 73) of patients with concordant MEG results while only 62.50% (30 of 48) of patients with dis-concordant MEG results were seizure free with a follow-up of 2-10 years. The differences of seizure-free rate between patients with concordant MEG results and dis-concordant MEG results were statistically significant. For patients with concordant MEG results, bilateral lesions on MRI are the only independent predictor of unfavorable seizure outcomes. For patients with discordant MEG results, duration of seizures is the only independent predictor of unfavorable seizure outcomes. CONCLUSIONS: Concordant MEG results are associated with favorable seizure outcomes. Bilateral lesions on MRI independently predict unfavorable seizure outcomes in patients with concordant MEG results while longer seizure durations independently predict unfavorable seizure outcomes in patients with dis-concordant MEG results.

Resective surgery for drug-resistant posttraumatic epilepsy: predictors of seizure outcome.

OBJECTIVE: The object of this study was to evaluate surgical outcomes and prognosis factors in patients with drug-resistant posttraumatic epilepsy (PTE) who had undergone resective surgery. METHODS: The authors retrospectively reviewed the records of all patients with drug-resistant PTE who had undergone resective surgery at Sanbo Brain Hospital, Capital Medical University, in the period from January 2008 to December 2016. All patients had a follow-up period of at least 2 years. Seizure outcomes were evaluated according to the International League Against Epilepsy (ILAE) classification. Patients in ILAE classes 1 and 2 during the last 2 years of follow-up were classified as having a favorable outcome; patients in all other classes were considered to have an unfavorable outcome. Univariate analysis and a multivariate logistic regression model in a backward fashion were used to identify the potential predictors of seizure outcomes. RESULTS: Among 90 patients with a follow-up of 2-10 years (mean ± standard deviation, 5.79 ± 2.84 years), 70% (63 patients) were seizure free, of whom 68.9% (62 patients) had an ILAE class 1 outcome and 1.1% (1 patient) had an ILAE class 2 outcome. Permanent neurological deficits were observed in 10 patients (11.1%). Univariate and multivariate analyses revealed that only the duration of seizures ≤ 8 years was an independent predictor of a favorable seizure outcome (OR 0.34, 95% CI 0.13-0.92). CONCLUSIONS: Resective surgery is an effective treatment for patients with drug-resistant PTE with an acceptable incidence of complications. The information on prognosis factors suggests that early surgery may offer more benefits to patients with drug-resistant PTE.

Surgical outcomes and prognostic factors of drug-resistant epilepsy secondary to encephalomalacia.

OBJECTIVE: To evaluate long-term outcomes and prognostic factors in patients who underwent surgical resection for drug-resistant epilepsy secondary to encephalomalacia. METHODS: A total of 143 patients with drug-resistant epilepsy who underwent surgical resection with a follow-up of at least 5 years were included. Seizure outcomes were evaluated based on the International League Against Epilepsy classification. Univariate analysis and a multivariate logistic regression model in a backward fashion were used to identify the potential predictors of seizure outcomes. RESULTS: Three months after surgery, 102 of 143 (71.3%) patients had achieved favorable seizure outcomes. Five years after surgery, 107 of 143 (74.8%) patients had achieved favorable seizure outcomes. Changes in the postoperative seizure status were observed in 22 of 143 (15.4%) patients during follow-up, but the difference in the seizure-free rate between 3 months and 5 years after surgery was not significant. Univariate and multivariate analyses revealed that only a monthly seizure frequency of >30 seizures (odds ratio = 3.42, 95% confidence interval = 1.19-9.76) and bilateral ictal onset rhythms (odds ratio = 4.46, 95% confidence interval = 1.61-12.39) were independent predictors of unfavorable seizure outcomes. SIGNIFICANCE: Surgical resection is an effective treatment for patients with drug-resistant epilepsy secondary to encephalomalacia. Knowledge of the predictors of seizure outcomes may help during preoperative counseling and selection of optimal candidates for epilepsy surgery among patients with drug-resistant epilepsy secondary to encephalomalacia.

Role of DNA Methylation and Adenosine in Ketogenic Diet for Pharmacoresistant Epilepsy: Focus on Epileptogenesis and Associated Comorbidities.

Epilepsy is a neurological disorder characterized by a long term propensity to produce unprovoked seizures and by the associated comorbidities including neurological, cognitive, psychiatric, and impairment the quality of life. Despite the clinic availability of several novel antiepileptic drugs (AEDs) with different mechanisms of action, more than one-third of patients with epilepsy suffer with pharmacoresistant epilepsy. Until now, no AEDs have been proven to confer the efficacy in alteration of disease progression or inhibition of the development of epilepsy. The ketogenic diet, the high-fat, low-carbohydrate composition is an alternative metabolic therapy for epilepsy, especially for children with drug-resistant epilepsy. Recently clinical and experimental results demonstrate its efficacy in ameliorating both seizures and comorbidities associated with epilepsy, such as cognitive/psychiatric concerns for the patients with refractory epilepsy. Of importance, ketogenic diet demonstrates to be a promising disease-modifying or partial antiepileptogenesis therapy for epilepsy. The mechanisms of action of ketogenic diet in epilepsy have been revealed recently, such as epigenetic mechanism for increase the adenosine level in the brain and inhibition of DNA methylation. In the present review, we will focus on the mechanisms of ketogenic diet therapies underlying adenosine system in the prevention of epileptogenesis and disease modification. In addition, we will review the role of ketogenic diet therapy in comorbidities associated epilepsy and the underlying mechanisms of adenosine.