Progress of clinical research studies on tuberous sclerosis complex-related epilepsy in China.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome, with 75.6%-83.5% and 54.1% patients presenting with epilepsy and drug-resistant epilepsy (DRE), respectively. Clinical studies on TSC, particularly surgical interventions, have achieved rapid and substantial progress. The TSC-Task Force Committee of the China Association Against Epilepsy (CAAE-TFTSC) was founded in 2012, and annual academic conferences on the surgical treatment of TSC-related epilepsy have been held since 2013. 'China experts' consensus on surgical treatment of TSC-related epilepsy' was published in 2019. This review focuses on surgical treatment, including resective surgery, neuromodulations, corpus callosotomy and mini-invasive ablations, as well as studies on phenotype, genotype and anti-seizure therapies of mammalian target of rapamycin inhibitor, vigabatrin and ketogenic diet in patients with TSC-related DRE in China.

Effect of current conduction for local epileptiform discharges in patients with temporal lobe epilepsy.

OBJECTIVES: The effects of current conduction were researched to confirm that it can decrease focal epileptogenicity in patients with temporal lobe epilepsy (TLE). METHODS: Data from 13 patients with mesial TLE were collected. After no less than two habitual seizures were captured during stereo-electroencephalogram monitoring, current conduction was measured in the hippocampus to a homemade, zero potential circuit board. The interictal spike, ripple, fast ripple, and ictal epileptogenicity index (EI) changes were analyzed in the hippocampus, amygdala, and anterior and middle temporal neocortex regions. RESULTS: Significant differences were found in the percentage of patients without spikes in the temporal neocortex between pre- and post-current conduction. Significant decreases in average ripple rates were found in the hippocampus and amygdala after current conduction. The percentage of fast ripple rate decrease in the hippocampus and amygdala was significantly higher than that in the temporal neocortex, and significant decreases were found in the fast ripple rate in the hippocampus from post- to pre-current conduction. Significant decreases were found in the EI values after current conduction in the amygdala and middle temporal lobe compared to the EI values before current conduction. CONCLUSION: After current conduction in patients with TLE, the spike rate decreases in the hippocampus, amygdala, and anterior and middle temporal neocortex, the ripple rate decreases in the hippocampus and amygdala, the fast ripple decreases in the hippocampus, and the EI decreases in the amygdala and middle temporal neocortex. Current conduction can reduce epileptogenicity in the hippocampus in mesial TLE.

Clinical Application of 7T Magnetic Resonance Imaging in Patients with Focal Cortical Dysplasia IIa and Epilepsy.

BACKGROUND: Focal cortical dysplasia (FCD) is one of the most important pathogenic findings in patients with extratemporal lobe epilepsy. Magnetic resonance imaging (MRI)-negative is the most important negative factor to predict postoperative seizure freedom; however, FCD-I and part of FCD-IIa are MRI-negative on routine MRI. OBJECTIVES: To explore the diagnostic values of 7T MRI and its new scan sequences in epilepsy patients with FCD-IIa. METHODS: To include patients with focal seizure and suspicious focal abnormal imaging on 3T MRI during preoperative evaluation and perform a 7T MRI scan with white matter-suppressed (WMS) and gray-white matter tissue border enhancement (GWBE) sequences, resective epilepsy surgery, and postoperative pathological finding of FCD-IIa. The preoperative qualitative and localization significance of 7T MRI and 3T MRI in lesions with FCD-IIa was compared, and then, the imaging characteristics of lesions with FCD-IIa on 7T MRI were analyzed. RESULTS: Ten cases were enrolled in this study. Seven tesla MRI presented high spatial resolutions and a high signal-to-noise ratio. WMS and GWBE could selectively suppress the signal of special tissue and improved the possibility of FCD findings. FCD-IIa showed abnormal thickness of gray matter and a blurring border and was hypointense on 7T MRI compared with 3T MRI. Seven patients showed improvement in the qualitative diagnosis strength grade of FCD, and 6 subjects showed improvement in the localization strength grade of the lesion border after careful reading of the 7T MR images. Significant differences were found in the qualitative diagnosis of FCD (p < 0.05) and localization of the lesion border (p < 0.05) between the neuroimaging diagnoses based on 3T MRI and the findings based on 7T MRI. CONCLUSION: 7T MRI with WMS and GWBE sequences shows application value in the preoperative imaging diagnosis of lesions with FCD-IIa in epilepsy patients.

Deep brain stimulation for pediatric pantothenate kinase-associated neurodegeneration with status dystonicus: A case report and literature review.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a type of inherited metabolic disorder caused by mutation in the PANK2 gene. The metabolic disorder mainly affects the basal ganglia region and eventually manifests as dystonia. For patients of dystonia, their dystonic symptom may progress to life-threatening emergency--status dystonicus. OBJECTIVE: We described a case of a child with PKAN who had developed status dystonicus and was successfully treated with deep brain stimulation (DBS). Based on this rare condition, we analysed the clinical features of PKAN with status dystonicus and reviewed the reasonable management process of this condition. CONCLUSION: This case confirmed the rationality of choosing DBS for the treatment of status dystonicus. Meanwhile, we found that children with classic PKAN have a cluster of risk factors for developing status dystonicus. Once children diagnosed with similar neurodegenerative diseases are under status dystonicus, DBS can be active considered because it has showed high control rate of this emergent condition.

Efficacy of deep brain stimulation for Tourette syndrome and its comorbidities: A meta-analysis.

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and vocal tics, often accompanied by comorbid disorders. Optional treatments for patients with TS include behavioral therapy, pharmacotherapy, and neurostimulation techniques. Deep brain stimulation (DBS) has been considered a therapeutic approach for refractory TS and its comorbid symptoms. However, systematic comparison is necessary to understand the therapeutic effect of DBS among patients with TS with various comorbid symptoms, demographic characteristics, or stimulation targets. Consequently, our research aimed to assess the clinical efficacy of DBS in alleviating the symptoms of TS and its comorbidities. A systematic literature search was conducted across five databases: PubMed, Web of Science, MEDLINE, Embase, and PsycINFO. The primary outcome was the mean change in the global score of the Yale Global Tic Severity Scale (YGTSS), which assesses the severity of tics. The secondary outcomes included mean improvement of comorbid symptoms, such as obsessive-compulsive behaviors (OCB), depression symptoms and anxiety symptoms. In total, 51 studies with 673 participants were included in this meta-analysis. Overall, the DBS led to a significant improvement in tic symptoms (p â€‹< â€‹0.001), as well as the comorbid obsessive-compulsive, depression, and anxiety symptoms with effect sizes of 1.88, 0.88, 1.04, and 0.76 accordingly. In the subgroup analysis, we found that striatum stimulation led to a more significant improvement in OCB in patients with TS compared to that observed with thalamic stimulation (p â€‹= â€‹0.017). The relationship between sex, age, and target with the improvement of tics, depression, and anxiety was not statistically significant (p â€‹= â€‹0.923, 0.438, 0.591 for different male proportions; p â€‹= â€‹0.463, 0.425, 0.105 for different age groups; p â€‹= â€‹0.619, 0.113, 0.053 for different targets). In conclusion, DBS is an efficient treatment option for TS, as well as the comorbid OCB, depression symptoms, and anxiety symptoms. It is important to highlight that stimulating the striatum is more effective in managing obsessive-compulsive symptoms compared to stimulating the thalamus.

Factors that Influence Subdural Hemorrhage Secondary to Intracranial Arachnoid Cysts in Children.

OBJECTIVE: This study aimed to investigate factors that influence subdural haemorrhage (SDH) secondary to intracranial arachnoid cysts (IACs) in children. METHODS: Data of children with unruptured IACs (IAC group) and those with SDH secondary to IACs (IAC-SDH group) were analyzed. Nine factors, sex, age, birth type (vaginal or caesarean), symptoms, side (left, right, or midline), location (temporal or nontemporal), image type (I, II, or III), volume, and maximal diameter, were selected. IACs were classified as types I, II, and III according to their morphological changes observed on computed tomography images. RESULTS: There were 117 boys (74.5%) and 40 girls (25.5%); 144 (91.7%) patients comprised the IAC group and 13 (8.3%) comprised the IAC-SDH group. There were 85 (53.8%) IACs on the left side, 53 (33.5%) on the right side, 20 (12.7%) in the midline region, and 91 (58.0%) in the temporal region. The univariate analysis showed significant differences in age, birth type, symptoms, cyst location, cyst volume, and cyst maximal diameter (P < 0.05) between the 2 groups. Logistic regression using the synthetic minority oversampling technique model showed that image type III and birth type were independent factors that influenced SDH secondary to IACs (ß0 = 4.143; ß for image type = -3.979; ß for birth type = -2.542) and that the representative area under the receiver-operating characteristic curve value was 0.948 (95% confidence interval, 0.898-0.997). CONCLUSIONS: IACs are more common in boys than in girls. They can be divided into 3 groups according to their morphological changes on computed tomography images. Image type III and caesarean delivery were independent factors that influenced SDH secondary to IACs.

Draft genome and transcriptome of Nepenthes mirabilis, a carnivorous plant in China.

OBJECTIVES: Nepenthes belongs to the monotypic family Nepenthaceae, one of the largest carnivorous plant families. Nepenthes species show impressive adaptive radiation and suffer from being overexploited in nature. Nepenthes mirabilis is the most widely distributed species and the only Nepenthes species that is naturally distributed within China. Herein, we reported the genome and transcriptome assemblies of N. mirabilis. The assemblies will be useful resources for comparative genomics, to understand the adaptation and conservation of carnivorous species. DATA DESCRIPTION: This work produced ~ 139.5 Gb N. mirabilis whole genome sequencing reads using leaf tissues, and ~ 21.7 Gb and ~ 27.9 Gb of raw RNA-seq reads for its leaves and flowers, respectively. Transcriptome assembly obtained 339,802 transcripts, in which 79,758 open reading frames (ORFs) were identified. Function analysis indicated that these ORFs were mainly associated with proteolysis and DNA integration. The assembled genome was 691,409,685 bp with 159,555 contigs/scaffolds and an N50 of 10,307 bp. The BUSCO assessment of the assembled genome and transcriptome indicated 91.1% and 93.7% completeness, respectively. A total of 42,961 genes were predicted in the genome identified, coding for 45,461 proteins. The predicted genes were annotated using multiple databases, facilitating future functional analyses of them. This is the first genome report on the Nepenthaceae family.

Diagnostic value of high-frequency oscillations for the epileptogenic zone: A systematic review and meta-analysis.

BACKGROUND: Delineation of the epileptogenic zone (EZ) is crucial during resective surgery in patients with epilepsy. In recent years, high-frequency oscillations, including fast ripples and ripples, have been considered promising biomarkers of the EZ. The objective of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic accuracy of fast ripples and ripples in identifying EZs. METHODS: The PubMed, Embase, and Cochrane databases were searched systematically. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A bivariate mixed-effects regression approach was used to obtain summary estimates of the sensitivity and specificity of fast ripples and ripples. RESULTS: Thirteen studies were included in this review (12 for fast ripples and eight for ripples). Fast ripples had a pooled sensitivity of 0.80 (95% confidence interval [CI], 0.62-0.91), a specificity of 0.72 (95% CI, 0.55-0.85), and a summary area under the curve of 0.82 (95% CI, 0.79-0.86). The threshold effect was detected for ripples, and the summary area under the curve was 0.75 (95% CI, 0.71-0.79), with a sensitivity of 0.38 (95% CI, 0.18-0.64) and specificity of 0.90 (95% CI, 0.70-0.97). CONCLUSIONS: Fast ripples are a biomarker of the EZ with moderate diagnostic accuracy; in contrast, ripples are not as effective.

Preliminary study on pathogenic mechanism of first Chinese family with PNKD.

Background: The first Chinese family with paroxysmal non-kinesigenic dystonia (PNKD) was confirmed to harbour a PNKD mutation. However, the pathogenic mechanism of the PNKD-causing gene mutation was unclear. Methods: Wild-type and mutant PNKD-L plasmids were prepared and transfected into the C6 cell line to study the distribution and stability of PNKD protein in C6 cells and its effect on the glutathione content. The blood and cerebrospinal fluid (CSF) of 3 PNKD patients and 3 healthy controls were collected. The differentially expressed proteins were identified using isobaric tags for relative and absolute quantitation. Furthermore, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed, and the protein-protein interaction network was constructed. Results: Wild-type PNKD protein was mainly distributed in the membranes, whereas mutant PNKD protein was distributed throughout the C6 cells. After transfection with mutant PNKD-L plasmid, the glutathione content decreased significantly in C6 cells; the stability of the mutant PNKD protein was significantly low. There were 172 and 163 differentially expressed proteins in CSF and plasma, respectively, of PNKD patients and healthy controls. For these proteins, blood microparticle and complex activation (classical pathway) were the common GO enrichment term, and complex and coordination cascade pathway were the common KEGG enrichment pathway. Recombinant mothers against decapentaplegic homolog 4 (SMAD4) was one of the differentially expressed proteins; it exhibited a relationship with the aforementioned enrichment GO terms and KEGG pathway. Conclusion: PNKD protein was mainly distributed in cell membranes. PNKD-L mutation affected subcellular localisation, PNKD protein stability, and glutathione content. SMAD4 was found to be a potential biomarker for PNKD diagnosis.

Interictal Discharge Pattern in Preschool-Aged Children With Tuberous Sclerosis Complex Before and After Resective Epilepsy Surgery.

Objective: To analyze the interictal discharge (IID) patterns on pre-operative scalp electroencephalogram (EEG) and compare the changes in IID patterns after removal of epileptogenic tubers in preschool children with tuberous sclerosis complex (TSC)-related epilepsy. Methods: Thirty-five preschool children who underwent resective surgery for TSC-related epilepsy were enrolled retrospectively, and their EEG data collected before surgery to 3 years after surgery were analyzed. Results: Twenty-three (65.7%) patients were seizure-free post-operatively at 1-year follow-up, and 37-40% of post-operative patients rendered non-IID on scalp EEGs, and patients with focal IIDs or generalized IID patterns on pre-operative EEG presented a high percentage of normal post-operative scalp EEGs. IID patterns on pre-operative scalp EEGs did not influence the outcomes of post-operative seizure controls, while patients with non-IID and focal IID on post-operative EEGs were likely to achieve post-operative seizure freedom. Patients with new focal IIDs presented a significantly lower percentage of seizure freedom than those without new focal IIDs on post-operative EEGs at 3-year follow-up. Conclusion: Over 1/3 children with TSC presented normal scalp EEGs after resective epileptsy surgery. Patients with post-operative seizure freedom were more likely to have non-IIDs on post-operative EEGs. New focal IIDs were negative factors for seizure freedom at the 3-year follow-up.

Independent temporal lobe epilepsy in patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare disease that involves multiple organs, including the brain; approximately 80%-90% of TSC patients exhibit TSC-associated epilepsy. Independent temporal lobe epilepsy (TLE), TSC-unrelated epilepsy, is particularly rare in patients with TSC. Here, we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography (EEG), postoperative pathological findings, and seizure outcome at follow-up. The patients were retrospectively enrolled at two centers; their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG. The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery. Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients. Furthermore, postoperative intelligence quotient improvement was evident in one patient, while the quality of life was improved in two patients at 12 months after surgery.

Chinese guideline on the application of anti-seizure medications in the perioperative period of supratentorial craniocerebral surgery.

Seizures are a common symptom of craniocerebral diseases, and epilepsy is one of the comorbidities of craniocerebral diseases. However, how to rationally use anti-seizure medications (ASMs) in the perioperative period of craniocerebral surgery to control or avoid seizures and reduce their associated harm is a problem. The China Association Against Epilepsy (CAAE) united with the Trauma Group of the Chinese Neurosurgery Society, Glioma Professional Committee of the Chinese Anti-Cancer Association, Neuro-Oncology Branch of the Chinese Neuroscience Society, and Neurotraumatic Group of Chinese Trauma Society, and selected experts for consultancy regarding outcomes from evidence-based medicine in domestic and foreign literature. These experts referred to the existing research evidence, drug characteristics, Chinese FDA-approved indications, and expert experience, and finished the current guideline on the application of ASMs during the perioperative period of craniocerebral surgery, aiming to guide relevant clinical practice. This guideline consists of six sections: application scope of guideline, concepts of craniocerebral surgery-related seizures and epilepsy, postoperative application of ASMs in patients without seizures before surgery, application of ASMs in patients with seizures associated with lesions before surgery, emergency treatment of postoperative seizures, and 16 recommendations.

The complete chloroplast genome sequence of Begonia coptidifolia.

Begonia (Begoniaceae) is a large, pantropically distributed genus, comprising more than 1900 species. Due to poorly available genome resources, the phylogeny of this species-rich genus is still challenged. B. coptidifolia is a newly discovered species of restricted distribution in Southern China, and its genetic relationship with the other Begonia species has not been reported. Therefore, in this study, we report for the first time its chloroplast genome for future phylogenetic analysis. The circular chloroplast genome of B. coptidifolia is 169,412 bp in length, with a GC content of 35.57%. Its large single-copy region is 75,937 bp, a small single-copy region is 18,362 bp, and two inverted repeat regions are 37,556 bp and 37,557 bp, respectively. The genome encodes 82 protein-coding genes, 8 ribosomal RNA genes, and 40 transfer RNA genes. Phylogenetic analysis indicated that B. coptidifolia is genetically closest to B. pulchrifolia.

Fast Ripples as a Biomarker of Epileptogenic Tuber in Tuberous Sclerosis Complex Patients Using Stereo-Electroencephalograph.

Objectives: To evaluate the value of fast ripples (FRs) (200-500 Hz) recorded with stereo-electroencephalograph (SEEG) in the localization of epileptogenic tubers in patients with tuberous sclerosis complex (TSC). Methods: Seventeen TSC patients who underwent preoperative SEEG examination and resective epilepsy surgery were retrospectively enrolled. They were divided into two groups according to the seizure control at 1-year postoperative follow-up. The occurrence frequencies of FRs were automatically counted, and the FR rate was calculated. The high FR rate was defined as FR rate ≧0.5. According to different positions, the contacts' locations were divided into three groups: inner of the tubers, the junction region of the tubers, and out of the tubers. The influence factors of postoperative seizure freedom were also analyzed. Results: Twelve patients reached postoperative seizure freedom at 1-year follow-up. In total, FRs were found in 24.2% of the contacts and 67.1% of the tubers in all assessed patients. There were 47 high FR rate contacts localized in the junction region of the tubers, which was 62.7% of the 75 high FR rate contacts in total and was 8.4% of the total 561 contacts localized in the junction region of the tubers. Total removal of epileptogenic tubers and total resection of the high FR rate tubers/contacts were associated with postoperative seizure freedom (P < 0.05). Conclusion: FRs could be extensively detected in TSC patients using SEEG, and high FR rate contacts were mostly localized in the junction region of the epileptogenic tuber, which could aid in the localization of epileptogenic tubers.

Preliminary analysis of the effect of vagus nerve stimulation in the treatment of children with intractable epilepsy.

BACKGROUND: Implant vagus nerve stimulation is an adjunctive treatment for intractable epilepsy when patients are not suitable for resective surgery. AIM: To identify the safety and efficacy of vagus nerve stimulation in children with intractable epilepsy and analyze the effects on different epilepsy syndromes. METHODS: Eligible children with intractable epilepsy were admitted to the study. We collected data from preoperative assessments as the baseline. During the follow-up time, we recorded the process of seizures (frequency, duration, and seizure type), the changes of drugs or parameters, the complications, etc. The mean reduction rate of seizures, response rate, and McHugh scale were chosen as the outcomes. RESULTS: A total of 213 patients were implanted with Tsinghua Pins vagus nerve stimulators, and the average age was 6.6 years. In the follow-up time of postoperative 3 mo, 6 mo, 12 mo, 18 mo, and 24 mo, the average reduction rate was 30.2%, 49.5%, 56.3%, 59.4%, and 63.2%, while the response rate was 21.8%, 62.5%, 57.1%, 69.2%, and 70.7%. In addition, implanted vagus nerve stimulation had different effects on epilepsy syndromes. The reduction rate of West syndrome increased from 36.4% (postoperative 6 m) to 74.3% (postoperative 24 m). The reduction rate of Lennox-Gastaut syndrome improved from 25.4% to 73.1% in 24 mo. The chi-square test of the five efficacy grades showed P < 0.05. The comparison between the 3-mo follow-up and the 6-mo follow-up showed P < 0.05, and the comparison between the 6-mo follow-up and the 24-mo follow-up showed P > 0.05. CONCLUSION: Vagus nerve stimulation is safe and effective in children with intractable epilepsy, and the seizure reduction occurred in a time-dependent manner. Moreover, patients with West syndrome may get the most benefits.

Magnetic resonance-guided laser interstitial thermal therapy versus stereoelectroencephalography-guided radiofrequency thermocoagulation for drug-resistant epilepsy: A systematic review and meta-analysis.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is a minimally invasive treatment for drug-resistant epilepsies (DRE), and stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) is also reported as a minimally invasive treatment in some cases with DRE. This study aimed to undertake a meta-analysis to assess the effectiveness and safety of the two approaches in treating DRE. METHODS: Databases, including PubMed, Embase, and Cochrane, were searched systematically up to November 2019. Our primary objective was to estimate the percentage of postoperative freedom from seizures and complications after MRgLiTT and SEEG-RFTC. The secondary objective was to estimate the rate of freedom from seizure after dividing the patients into groups according to the etiology of the epilepsy. RESULTS: Twenty-six studies, with a total number of 804 patients, were identified, 16 studies with MRgLiTT (414 patients) and 10 with SEEG-RFTC (390 patients). In total, significant difference was found in the postoperative rate of freedom from seizure between patients with MRgLiTT (65 %; 95 % CI 56-74 %) and those with SEEG-RFTC (23 %; 95 % CI 10-39 %) (P = 0.00), and there was high heterogeneity across groups. After dividing the patients according to etiology, those with MRgLiTT in both the hypothalamic hamartoma group (99 %; 95 % CI 92 %-100 %) and the temporal lobe epilepsy group (59 %; 95 % CI 53 %-65 %) achieved great efficacy and low heterogeneity, and patients with temporal lobe epilepsy and mesial temporal sclerosis (MTS) did not achieve better seizure control than non-MTS patients did (OR = 1.46; 95 % CI [0.88, 2.41]; P = 0.142). For the patients treated with SEEG-RFTC, those in the periventricular nodular heterotopias group obtained the highest percentage of freedom from seizure (56 %; 95 % CI 23 %-86 %). The overall complication rate across all samples was low in the two approaches (5%; 95 % CI 3%-8%). CONCLUSIONS: MRgLiTT and SEEG-RFTC are both safe, minimally invasive treatments for patients with DRE. Patients treated with MRgLiTT had an overall higher postoperative rate of freedom from seizure than those treated with SEEG-RFTC.

Clinical phenotypes, genotypes and treatment in Chinese dystonia patients with KMT2B variants.

BACKGROUND: KMT2B-related dystonia is a recently discovered hereditary dystonia that mostly occurs in childhood. This dystonia usually progresses to generalized dystonia with cervical, cranial, pharynx and larynx involvement. Our study summarizes genotype-phenotype features and deep brain stimulation (DBS) efficacy observed with KMT2B-related dystonia patients in China. METHODS: We identified 20 patients with KMT2B variations from dystonia samples with a gene panel and whole exome sequencing. Genetic, clinical and treatment analyses of these patients with KMT2B mutations were further conducted. RESULTS: We summarized the genotype and phenotypic characteristics of KMT2B-related patients in China, including 16 sporadic patients and 3 pedigrees (including 4 patients). Thirty-five percent (7/20) of patients had been published previously. The age of onset was between 1 month and 24 years (average 6.90 ± 5.72 years). Sixty-five percent (13/20) of patients had onset from lower limbs. Upper limbs or larynx accounted for 15% (3/20) and 20% (4/20) of patients, respectively. In the same family, male patients tended to have more severe symptoms than female patients. Carriers of KMT2B variants may present with nonmotor symptoms without dystonia. Abnormal endocrine metabolism could also be seen in our patients, including advanced bone age that had never been reported previously. Nine of our patients underwent DBS surgery. The mean follow-up time was 4.9 (range 1.3-16) months after DBS, and perceptible improvement of clinical symptoms were observed. CONCLUSIONS: The genotypic and phenotypic spectra of Chinese KMT2B-related dystonia patients were further expanded. DBS surgery might be the preferred option for severe KMT2B-related dystonia patients till now.

The Metabolic Activity of Caudate and Prefrontal Cortex Negatively Correlates with the Severity of Idiopathic Parkinson's Disease.

Positron emission tomography (PET) scan with tracer [18F]-fluorodeoxy-glucose (18F-FDG) is widely used to measure the glucose metabolism in neurodegenerative disease such as Idiopathic Parkinson's disease (IPD). Previous studies using 18F-FDG PET mainly focused on the motor or non-motor symptoms but not the severity of IPD. In this study, we aimed to determine the metabolic patterns of 18F-FDG in different stages of IPD defined by Hoehn and Yahr rating scale (H-Y rating scale) and to identify regions in the brain that play critical roles in disease progression. Fifty IPD patients were included in this study. They were 29 men and 21 women (mean±SD, age 57.7±11.1 years, disease duration 4.0±3.8 years, H-Y 2.2±1.1). Twenty healthy individuals were included as normal controls. Following 18F-FDG PET scan, image analysis was performed using Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST). The metabolic feature of IPD and regions-of-interests (ROIs) were determined. Correlation analysis between ROIs and H-Y stage was performed. SPM analysis demonstrated a significant hypometabolic activity in bilateral putamen, caudate and anterior cingulate as well as left parietal lobe, prefrontal cortex in IPD patients. In contrast, hypermetabolism was observed in the cerebellum and vermis. There was a negative correlation (p=0.007, r=-0.412) between H-Y stage and caudate metabolic activity. Moreover, the prefrontal area also showed a negative correlation with H-Y (P=0.033, r=-0.334). Thus, the uptake of FDG in caudate and prefrontal cortex can potentially be used as a surrogate marker to evaluate the severity of IPD.

Metabolic covariance networks combining graph theory measuring aberrant topological patterns in mesial temporal lobe epilepsy.

OBJECTIVE: We aimed to study the networks' mechanism of metabolic covariance networks in mesial temporal lobe epilepsy (mTLE), through examining the brain value of fluorine-18-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET). METHODS: 18 F-FDG-PET images from 16 patients with mTLE were analyzed using local and global metabolic covariance network (MCN) approaches, including whole metabolic pattern analysis (WMPA), hippocampus-based (h-) MCN, whole brain (w-) MCN, and edge-based connectivity analysis (EBCA). RESULTS: WMPA showed a typical ipsilateral hypometabolism and contralateral hypermetabolism pattern to epileptic zones in mTLE. h-MCN revealed decreased hippocampus-based synchronization in contralateral regions. w-MCN exhibited a disrupted metabolic network with globally increased small-world properties and regionally decreased nodal metrics in the ipsilateral hemisphere. Hippocampus (h)-EBCA and whole brain EBCA (w-EBCA) both detected a reduced-connectivity dominated metabolic covariant network. Moreover, the reduced interhemisphere connectivity seemingly played a major role in the aberrant epileptic topological pattern. CONCLUSION: From a metabolic point of view, we demonstrated the damaging effects with reduced contralateral intranetwork metrics properties and the compensatory effects in contralateral intranetworks with increased network properties. However, the import role of significant reduced interhemisphere connection has rarely been reported in other mTLE studies. Taken together, 18 F-FDG-PET MCN analysis provides new evidence that the mTLE is a system neurological disorder with disrupted networks.