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Objective To study the clinical phenotype and prognosis of children diagnosed with early-onset epileptic encephalopathy (EOEE) and pachygyria-lissencephaly,and to explore the potential genetic factors.Methods The clinical data of 65 children between December 2005 and December 2016 was obtained and analyzed.And the whole exome sequencing was analyzed by using second generation sequencing technology.Results Among 65 children,17 cases (26.1％) were diagnosed as lissencephaly,34 cases (52.3 ％) were pachygyria,and 14 cases (62.6％)were pachygyria with lissencephaly.Thirteen cases (20.0％) were infantile spasms,9 cases (13.8％) were ohtahara syndrome,3 cases (4.6％) were early myoclonic epileptic encephalopathy,and 40 cases (61.6％) were non-symptomatic EOEE.Six cases (6/65 cases,9.2％) were associated with dyskinesia,of whom 3 cases showed dystonia,2 cases of limb tremor,1 case of dancing-like movements.Electroencephalophalogram (EEG) showed serious multifocal discharge,40 cases had massive multifocal discharge.Brain images showed that simple pachygyria was more common (34/65 cases,52.3 ％).Among them,focal pachygyria was more common (25/34 cases,73.5 ％),mostly involving in the frontoparietal lobe (11/25 cases,44.0％).Copy number variations and whole exon sequencing were performed on 61 patients.Copy number variation was detected in 1 patient.There were 2 cases of lissencephaly-1/platelet-activating factor acetylhydrolase isoform 1B (LIS1/PAFAH1B1) mutation,1 case of syntaxin-blinding protein 1 (STXBP1)mutation,1 case of Aristaless-related homeobox (ARX) mutation,and 1 case of dynein cytoplasmic 1 heavy chain 1(DYNC1H1) mutation.The follow-up time varied from 1 year to 8 years [(3.5 ± 1.4) years],in which 20 cases had clinical seizures under control but 45 cases out of control.Conclusion Infantile spasms and non-syndromic EOEEare more common in children diagnosed with EOEE and pachygyria-lissencephaly.A small number of cases have dyskinesia.EEG shows serious abnormalities,mostly multifocal discharge.Brain images show simple pachygyria is more common,mostly involving in the frontoparietal lobe.Common gene mutations are LIS1/PAFAH1B1,STXBP1,ARX.Gene mutations can lead to both clinical manifestations of cortical deformity and EOEE,and genetic factors play an important role in children with brain developmental deformity and epilepsy.
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The increasing identification of genetic causes for epilepsy over the recent years improves the understanding of the underlying epileptog enic process,and allows for the possibility of directed therapeutic approaches.An ideal antiepileptic therapy consists of a drug which is able to influence the functional changes caused by a specific pathogenic variant.In this review,we describe the current precise medicine approaches in genetic epilepsies.Currently established or investigated precise medicine treatments include the ketogenic diet in patients with glucose transporter typel (GLUT1) deficiency,sodium channel blockers in patients with KCNQ2 mutations,and mechanistic target of rapamycin (mTOR)-inhibitors in patients with SCN2A and SCN8A mutations.These predominantly represent already available treatments that were repurposed for use in epilepsy.The development of new therapeutic agents aiming at targets identified in genetic epilepsies will advance epilepsy treatment considerably.
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Objective To analyze the clinical data and TUBB4A mutation of hypomyelination with atrophy of the basal ganglia and cerebellum (HABC)in a family,thus to provide accurate genetic counseling and prenatal diagno-sis for this family with HABC,and also to provide clinical experience for the diagnosis of HABC in China.Methods The clinical data of the proband and her family members were collected at the Department of Pediatrics,Peking Univer-sity First Hospital,December 201 4,including medical history,physical signs,and brain MRI,biochemical tests and metabolic disease screening.The associated gene of hereditary leukoencephalopathy was screened for the proband and her family members were screened by targeting -high -throughput sequencing technology,and then the genetic varia-tions were verified by Sanger sequencing.With those detection methods,the gene mutation was confirmed,and then ge-netic features were analyzed.Results Clinical features were as follows:nystagmus as the first symptom,and motor and mental retardation,dystonia and ataxia followed.Brain MRI indicated hypomyelination of white matter and atrophy of the basal ganglia and cerebellum.The clinical diagnosis of HABC was established based on the clinical features and brain MRI features above.Genetics features showed that one novel TUBB4A c.974G >T heterozygous missense muta-tion was found from the proband,which caused an amino acid change from the Trp into Leu (p.Trp325Leu).Both of her parents with normal phenotype were of wild -type in this site.Conclusions The proband from this family was diagnosed clinically based on her clinical data.One novel TUBB4Ac.974G > T (p.Trp325Leu)was founded in this study.Therefore,the spectrum of TUBB4A mutation will be expanded.In addition,this study elucidated clinical and genetic characteristics in this family with HABC,which may lay a solid foundation for the accurate genetic counseling and prenatal diagnosis.This study reported the first case of HABC caused by TUBB4A mutation in China.
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Objective To explore the potential changes of connexin Cx36 in hippocampus and cortical neurons of rats with hyperthermia -induced convulsion.Methods Rats were divided into 2 groups according to the random number table method:normal control group and experimental group.Febrile convulsion model was elicited through im-mersion in warm water.The experimental group was generated following febrile convulsion model:hyperthermia group and febrile convulsion group.Among normal control group,hyperthermia group and febrile convulsion group,western blot analysis and immunofluorescence labeling techniques were used to examine the expression of Cx36 protein in the hippo-campus and cortex area.One -Way ANOVA was used to compare the mean of multiple sample,the LSD test was used to compare the two means.Tamhane′s test was used when variance were uneven.Results The incubation period,seizure duration and temperature were (4.39 ±0.08)min,(5.38 ±0.07)min,(41 .87 ±0.06)℃ after hyperthermia-in-duced convulsion,respectively.Western blot analysis showed that the expression of Cx36 protein in the hippocampus and cortex area decreased gradually after 1 0 times of seizure in normal control group,hyperthermia group and febrile convulsion group,and the febrile convulsion group decreased most obviously.Compared with normal control group and hyperthermia group,respectively,in febrile convulsion group Cx36 expression obviously decreased in the hippocampus and cortex in rats with 1 ,5,1 0 seizure times induced by hyperthermia,and with the increase of number of induced con-vulsion,the expression of Cx36 was significantly decreased in the cortex (0.1 04 ± 0.01 2)and CA1 (0.091 ± 0.01 1 ),CA3 (0.090 ±0.01 1 )and DG (0.092 ±0.01 2)areas of hippocampal neurons compared with the normal control group (0.21 2 ±0.01 7,0.1 67 ±0.01 3,0.1 59 ±0.01 4,0.1 71 ±0.01 3)and the hyperthermia group (0.1 89 ± 0.006,0.1 44 ±0.008,0.1 29 ±0.005,0.1 65 ±0.01 1 )(all P <0.05).Furthermore,the extent of reduction in Cx36 expression seemed to correlate with the number of seizures.Conclusion With the increase of thermal seizure frequen-cy,Cx36 expression of rats was decreased obviously which may lower convulsion threshold and lead to recurrent seizures.
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Objective To evaluate the effectiveness of autologous platelet-rich gel (APG)in the repair of diabetic foot ulcers.Methods This study was a single-center,prospective,randomized controlled trial.A total of 60 patients with diabetic foot ulcers (Wagner grade 2 - 3 )were randomly divided into autologous APG group (treatment group)and recombinant bovine basic fibroblast growth factor gel group (control group).After 8 weeks, we compared wound healing rate and wound healing time at five levels (overall ulcer,superficial ulcer,sinus ulcer, Wagner 2 and Wagner 3)in the two groups.Results In APG treatment group and control group,the healing rate of overall sample ulcer (93.33% vs .63.33%,P =0.005),sinus ulcer (84.62% vs .36.36%,P =0.033),Wagner 3 (81.82% vs .30%,P =0.030)differed significantly,but did not significantly differ in superficial ulcer (100%vs .78.95%,P =0.106)or Wagner 2 (100% vs .80%,P =0.106).Ulcer healing time was 31 d vs .41.5 d,23 d vs .32 d,32 d vs .56 d,25 d vs .32 d,38 d vs .56 d,with significant difference between the two groups (P <0.05). Conclusion Autologous platelet-rich gel can effectively increase the curative rate of diabetic foot and shorten healing time.
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The pathogenesis of status epilepticus is closely associated with brain injury. Some animals experiments have proved that the activity of calcium / calmodulin-dependent protein kinase 2 ( CaM kinase Ⅱ ) ,oxidative stress, and the imbalance of nervous immune-endocrine factors are not only involved in the mechanisms of status epilepticus, but also act as the initial factor in neuronal injury. The pathophysiological changes after SE,such as acute brain ischemia, hypoxia and the reduced glucose utilization, over-excited neurons, N-methyl-Daspartate (NMDA) and non-NMDA receptor activated, a large amount of cation influx, can give rise to acute necrosis of neurons, also initiate the expression of apoptotic genes, at last leading to apoptosis by cell apoptotic enzymes cascade reaction. Studies have found that the pathway of death receptor activation, mitochondrial damage and endoplasmic reticulum stress mediated the neuronal apoptotic signal transduction after SE.