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Long-term outcomes and prognosis factors of vagus nerve stimulation in patients with Refractory Epilepsy

Acta Epileptologica 2022年第3期5卷 201-207页

作者： Cuiping Xu Hua Lin Jiwen Xu Xiaohua Zhang Guiliang Hao Qiang Qiang Liu Chengyun Ding Shan Wang Quanjun Zhao Xiaojun Bai Kui Chen Duanyu Ni Yongjie Li Tao Yu Yuping Wang Department of Functional Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Functional Neurosurgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of epilepsy First Affiliated HospitalGeneral Hospital of People’s Liberation ArmyBeijing 100048China Department of Neurosurgery The 306th Hospital of PLABeijing 100101China Department of Neurology Beijing Friendship HospitalBeijing 100050China

Background:Vagus nerve stimulation(VNS)is an effective treatment for patients with Refractory Epilepsy,yet with varied predictive factors and heterogeneous long-term outcomes.Adjustment of VNS parameters is critical for obtaining favorable efficacy.In this study,we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with Refractory Epilepsy.Methods:Eighty-six patients(59 males and 27 females)who underwent VNS implantation for treatment of Refractory Epilepsy between May 2016 and May 2017 at five epilepsy Centers were enrolled.The clinical data,including sex,age at epilepsy onset,VNS implantation,epilepsy duration,seizure type,MRI findings,history of neurosurgical operations,and responder rate(responders were those with≥50%seizure reduction),were analyzed.Results:Four-year follow-up data were available for 76 patients(53 males and 23 females).The mean current intensity at the last follow-up was 1.8±0.3 mA(range:0.75–2.5 mA).The mean seizure reduction was 36.2%at 6 months,38.5%at 1 year,69.4%at 3 years,and 56.7%at 4 years.A favorable outcome of≥50%reduction in seizure frequency occurred in 40.0%of the patients at 6 months,55.9%at 1 year with 4 patients being seizure-free,63.2%at 3 years with 5 patients being seizure-free,and 68.4%at 4 years with 5 patients being seizure-free.Earlier onset age(PRefractory Epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment.The stimulation efficacy increases over time after implantation,and earlier exposure to VNS improves the prognosis.

关键词： Refractory Epilepsy Vagus nerve stimulation Generalized seizures Long-term efficacy

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Brain stimulation for treatment of Refractory Epilepsy

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Chinese Medical Journal 2013年第17期126卷 3364-3370页

作者： GE Yan HU Wei LIU Chong ZHANG Jian-guo MENG Fan-gang Beijing Neurosurgical Institute Capital Medical University Beijing 100050 China Department of Neurology Mayo Clinic Rochester MN 55905 USA Department of Neurosurgery Tiantan Hospital Capital Medical University B eijing 100050 China

Objective We review the targets of the deep brain and the responsive neurostimulation system （RNS） to identify the best optimal stimulation parameters and the best mode of stimulation, whether cyclical, continuous, or smarter. Data sources This review is based on data obtained from published articles from 1950 to 2013. To perform the PubMed literature search, the following keywords were input： deep brain stimulation （DBS）, RNS, and Refractory Epilepsy. Study selection Articles containing information related to brain stimulation or RNS for the treatment of Refractory Epilepsy were selected. Results The currently available treatment options for those patients who resist multiple antiepileptic medications and surgical procedures include electric stimulation, both direct and indirect, of brain nuclei thought to be involved in epileptogenesis. The number of potential targets has increased over the years to include the anterior nucleus of the thalamus, the centromedian nucleus of the thalamus, the hippocampus, the subthalamic nucleus, the caudate nucleus, and the cerebellum, among others. The results of a randomized controlled trial and the RNS trial were published to reveal the effectiveness. Conclusions Although statistically significant reductions in seizures have been observed using several different stimulation techniques, including vagus nerve stimulation, DBS, and RNS, these effects are currently only palliative and do not approach the efficacy comparable with that seen in resection in appropriately selected patients. More research is needed to determine optimal stimulation targets and techniques as well as to determine which epilepsy patients will benefit most from this technology.

关键词： brain stimulation target Refractory Epilepsy stimulation parameters

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Brain-derived neurotrophic factor expression is higher in brain tissue from patients with Refractory Epilepsy than in normal controls

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Neural Regeneration Research 2011年第29期6卷 2262-2266页

作者： Yudan Lv Jiqing Qiu Zan Wang Li Cui Hongmei Meng Weihong Lin Department of Neurology First Hospital of Jilin University Changchun 130021 Jifin Province China

The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with Refractory Epilepsy are associated with brain-derived neurotrophic factor expression alterations.

关键词： Refractory Epilepsy brain-derived neurotrophic factor seizure focus brain injury neural regeneration

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MicroRNAs as biomarkers in molecular diagnosis of Refractory Epilepsy

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Chinese Neurosurgical Journal 2016年第4期2卷 223-228页

作者： Xiaofeng Wang Hang Yin Alyson M.Rich7 Yuqiang Sun Zeshi Tan Xiaodong Luo Ningwei Che Department of Neurosurgery Dalian No.24 high school Dalian Liaoning 116044 People's Republic of China Department of Psychiatry Department of Neurosurgery The Second Affiliated Hospital of Dalian Medical University 467 Zhongshan RoadShahekou Dalian Liaoning 116044 People's Republic of China

MicroRNA (miRNA) is a type of endogenous non-coding RNA that can regulate cell proliferation, differentiation, invasion, apoptosis and several other biological activities by specially inducing gene silencing, and thereby is related to development and disease in life course. In recent years, researchers have found that miRNAs are closely related with Refractory Epilepsy. MiRNAs can intervene in the modification of mRNAs, the synthesis of proteins and some the connectivity of signal pathways in pathogenesis of epilepsy. Furthermore, some miRNAs in neurons are of great importance in neuronal differentiation. Therefore, miRNA may play a very important role in the occurrence, development and episodes of Refractory Epilepsy. These discoveries can provide a new direction for the research of pathogenesis, diagnostic methods and therapeutic approach of Refractory Epilepsy. Although research about miRNA and intractable epilepsy has progressed, more remains to be done before miRNA can be used in clinical diagnosis and treatment strategies. This paper focuses on the research progress of molecular diagnosis about miRNA in intractable epilepsy.

关键词： MicroRNA Refractory Epilepsy Biomarker Diagnosis

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Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to Refractory Epilepsy in Chinese Han children

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Neural Regeneration Research 2009年第11期4卷 901-906页

作者： Guangxin Wang Zuocheng Yang Ruifeng Jin Ruopeng Sun Department of Paediatrics Qilu Hospital of Shandong University Jinan 250012 Shandong Province China Department of Paediatrics Third Xiangya Hospital of Central South University Changsha 410013 Hunan Province China Institute of Paediatrics Qilu Children's Hospital of Shandong University Jinan 250022 Shandong Province China

BACKGROUND： There are two hypotheses for the underlying cause of Refractory Epilepsy：＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in Refractory Epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with Refractory Epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with Refractory Epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of Refractory Epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the Refractory Epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and Refractory Epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the Refractory Epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The di

关键词： brain-derived neurotrophic factor gene multidrug resistance 1 gene single nucleotide polymorphisms children Refractory Epilepsy

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Pharmacokinetic, pharmacodynamic, and neurochemical investigations of lamotrigine-pentylenetetrazole kindled mice to ascertain it as a reliable model for clinical drug-resistant epilepsy

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Animal Models and Experimental Medicine 2020年第3期3卷 245-255页

作者： Sandeep Kumar Rajesh K.Goel Department of Pharmaceutical Sciences&Drug Research Punjabi UniversityPatialaPunjabIndia

Background:Pentylenetetrazole kindling has long been used for the screening of investigational antiseizure drugs.The presence of lamotrigine,at a very low dose,does not hamper kindling in mice;rather it modifies this epileptogenesis process into drug-resistant epilepsy.The lamotrigine-pentylenetetrazole kindled mice show resistance to lamotrigine,phenytoin,and carbamazepine.It may also be possible that other licensed antiseizure drugs,like the mentioned drugs,remain ineffective in this model;therefore,this was the subject of this study.Methods:Swiss albino mice were kindled with pentylenetetrazole for 35 days in the presence of either methylcellulose vehicle or lamotrigine(subtherapeutic dose,ie,5 mg/kg).Vehicle vs lamotrigine-kindled mice were compared in terms of(a)resistance/response toward nine antiseizure drugs applied as monotherapies and two drug combinations;(b)lamotrigine bioavailability in blood and brain;(c)blood-brain barrier integrity;and(d)amino acids and monoamines in the cerebral cortex and hippocampus.Results:Lamotrigine vs vehicle-kindled mice are similar(or not significantly different P>.05 from each other)in terms of(a)response toward drug combinations;(b)lamotrigine bioavailability;and(c)blood-brain barrier integrity except for,significantly(P<.05)reduced taurine and increased glutamate in the cerebral cortex and hippocampus.Aside from these,lamotrigine-kindled mice show significant(P<.05)resistant to lamotrigine(15 mg/kg),levetiracetam(40 mg/kg);carbamazepine(40 mg/kg),zonisamide(100 mg/kg),gabapentin(224 mg/kg),pregabalin(30 mg/kg),phenytoin(35 mg/kg),and topiramate(300 mg/kg).Conclusion:Lamotrigine-pentylenetetrazole kindling takes longer to develop(~5 weeks)in comparison to lamotrigine-amygdale(~4 weeks)and lamotriginecorneal(~2 weeks)kindling models.However,drug screening through this model may yield superior drugs with novel antiseizure mechanisms.

关键词： animal models drug-resistant epilepsy kindling lamotrigine Refractory Epilepsy

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A case report of microcephaly and refractory West syndrome associated with WDR62 mutation

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Acta Epileptologica 2020年第1期2卷 19-24页

作者： Ping Zhou Xin Ding Qi Zeng Huafang Zou Jianxiang Liao Dezhi Cao Neurology Department Shenzhen Children’s HospitalShenzhenGuangdong 518038China. Division of Growth Development and Mental Health of Children and AdolescenceChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China.

The autosomal recessive form of primary microcephaly(MCPH)is a rare disorder characterized by microcephaly with variable degree of intellectual disability.WDR62 has been reported as the second causative gene of MCPH2.West syndrome is a severe epilepsy syndrome composed of the triad of spasms,hypsarrhythmia,and mental retardation.There are limited clinical reports regarding WDR62 mutation and West syndrome.Here we report a boy who was identified with WDR62 mutation and was followed up from age 3 months to 5 months and 14 days.He had the first seizure as the classic epileptic spasm at the age of 3 months.Psychomotor retardation was noted before the seizure occurred.The head circumference was 38.5 cm(SD 2.6)when he was 4 months old,no dysmorphic facial features were observed.He couldn’t support his head steadily or turn over.He was able to laugh when tricked by the parents,but couldn’t track the sound and light.At the early stage,the electroencephalogram showed multifocal discharges,which evolved into hypsarrhythmia one month later,and brain MRI showed developmental malformation of cerebral gyrus.Two heterozygous mutations were identified in WDR62 by whole exome sequencing c.1535G>A,p.R512Q and c.2618dupT,p.K874Qfs40.The patient was administrated with oral sodium valproate,nitrazepam,intramuscular adrenocorticotropic hormone for 2 weeks,and followed by prednisone,levetiracetam,topiramate and vigabatrin.However,there was no significant improvement on the seizure control after these treatments.According to the genetic report and clinical manifestation,we speculated that the WDR62 compound heterozygous mutation is responsible for the serious clinical phenotype.

关键词： Autosomal recessive primary microcephaly 2 WDR62 West syndrome Refractory Epilepsy

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Long-Term Impact in the Quality of Life of Patients with Drug-Resistant epilepsy That Use Cannabidiol

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Neuroscience & Medicine 2021年第4期12卷 103-113页

作者： Gabriela Pesántez Ríos Ignacio Pascual Pascual Ximena Pesántez Ríos Luciana Armijos Estefanía Chediak Hugo Navarrete Zambrano Ruth Jimbo Galo Pesantez Cuesta Servicio de Neurología Pediátrica Centro Nacional de Epilepsia Quito Ecuador Universidad Autónoma de Madrid Madrid Espa&#241 a Servicio de Neurología Pediátrica Hospital Universitario La Paz Madrid Espa&#241 a Centro de Investigación para la Salud en América Latina (CISeAL) Quito Ecuador Facultad de Medicina Pontificia Universidad Católica del Ecuador Quito Ecuador

Introduction: epilepsy is considered a chronic neurological condition that manifests itself with seizures, where 30% - 40% of patients do not achieve control of their seizures despite proper management. Seizures represent a significant limitation in the patient’s daily activities and are often accompanied by emotional and relational difficulties that have a great impact on the quality of life of the patient and their families. Cannabidiol (CBD) has been found to be effective in controlling seizures and may also improve cognitive and behavioral abilities. Material and Methods: The Quality of Life of the Patient with epilepsy (CAVE) scale was applied to patients with refractory epilepsies who use Cannabidiol (CBD) added to their base therapy, before the use of CBD and after 12 months of follow-up. The presentation of collateral effects was also evaluated. Results: Out of 34 patients, 26 (76.5%) increased their CAVE value at the end of the study and only 1 (2.9%) decreased. 19 (55.9%) improved in learning and behavior, 55.8% in the frequency of seizures and 79.4% reported a decrease in the intensity of seizures. There were other positive side effects such as improvement in alertness, language, sleep and behavior. The main side effects were mild and transitory, including drowsiness, and constipation. There was a correlation between the global perception of improvement and seizure control. Conclusions: This study shows that in the long term CBD improves the quality of life of patients with refractory epilepsies, through the control of seizures and the improvement of cognitive and behavioral functions.

关键词： Quality of Life Refractory Epilepsy Cannabidiol

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