Objective To explore the clinical features of juvenile Parkinson's disease(PD).Methods The clinical materials in 28 patients with juvenile Parkinsonism were analysed retrospectively.Results Among the 28 cases, 5 patients from 3 families had familial history and presented autosomal recessive inheritance(AR-JP).The sympotoms of the parkinsonian triad were mild and unsymmetric.The disease progressed slowly.Hyperreflexia and diurnal fluctuation of sympotoms were often seen in these patients,but brain CT and MRI were often nomal.Response to levodopa was satisfactory,but dopa-induced motor fluctuations occurred early. In contrast to sporadic juvenile PD,AR-JP tended to have earlier age of onset( 20.6?5.68 years),longer duration of progression of parkinsonian signs and symptoms( 9.5?5.77 years),more frequent presence of hyperreglexia and diural fluctuation,and more frequent appearance of dopa-related motor fluctuations.Conclusion The clinical features of patients with juvenile PD are peculiar and juvenile PD may be an independent disease entity.AR-JP is different from sporadic juvenile PD,which suggests that there may be different pathogenesis between these two subtypes.

Objective To explore the clinical features of autosomal recessive juvenile Parkinson disease(AR-JP).Methods The clinical materials of 28 patients from 15 families with AR-JP were analyzed retrospectively.Results The onset of all the patients was insidious and the mean age was 26.1 years old.In 23 patients(82.1%),the symptoms began at one limb or one side and progressed bilaterally in a mean time of((4.7?)3.6) years.Bradykinesia(100%),rigidity(100%),resting tremor (85.7%),postural instability(60.7%),hyperreflexia(53.6%),dystonia(32.1%) and diurnal fluctuations with sleep benefit(89.2%) were the cardinal symptoms.The mean improved Webster score was(11.2?)6.1.The mean maintenance dose of DOPA-preparation was((0.40?)0.28) g/d.The mean UPDRS motor score was(27.9?)10.3 before treatment and it decreased to(6.7?)5.4 after therapy(P

Objective To study the clinical features and genetic mutation frequency of spinocerebellar ataxia (SCA) type 6 from Chinese kindreds. Methods The SCA6 (CAG)n trinucleotide repeat mutations were detected using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) techniques in 330 patients with autosomal dominant SCA from 160 kindreds and 77 sporadic SCA patients, and the abnormal alleles fragments were sequenced by ABI377 DNA sequencing machine. The clinical features were assessed and cranial MRI examinations were performed in these patients.Results 6 patients from 4 SCA6 Chinese kindreds had abnormal SCA6 alleles with CAG repeat expanded to 25 and 26, respectively, of which 2.5% was about the positive rate, while CAG repeat of normal SCA6 allele ranged from 5 to 17. The basic characteristics of SCA6 patients were slowly progressive cerebellar ataxia and purely cerebellar atrophy.Conclusion SCA6 is one seldom subtype of SCA in Chinese patients with its characteristics both in clinic and imaging in contrast to other subtypes.

BACKGROUND: Nicotine, which is a known central nervous system stimulant, appears to be the neuroprotective factor of Parkinson disease(PD). It has been reported that PD patients' symptoms such as trembling,rigor, hypokinesia are ameliorated during smoking, but its mechanism still keeps unclear.OBJECTIVE: To observe the effects of nicotine on gene expression levels of dopamine D1 and D2 receptors (D1R,D2R)in striatum of rats and analyze the possible mechanism of behavioral changes of rats induced by nicotine.DESIGN:Randomized and controlled experiment.SETTING:Institute of Neurology, Xiangya Hospital, Central South University.MATERIALS :Twenty-four SD rats aged at 10 weeks were chosen,weighing 180-200 g. Nicotine (Sigma),revert AidTM M-Mulv reverse transcriptase (MBI Fermentas,USA), polymerase chain reaction (RCR,Beckman),densitometric scanning imaging system (Stratagene Eagle Eye Ⅱ ,USA).METHODS :This experiment was carried out in the Laboratory of Institute of Neurology, Xiangya Hospital,Central South University from July 2001 to July 2002. These rats were divided into two groups: control group (n=12)and nicotine group(n=12). The level of D1 and D2 receptors on striatum of rats was estimated at the timepoint of thirty-minute after chronic nicotine administration (4 mg/kg per day s.c.), and the behavioral activities were also recorded at the same timepoint for thirty minutes. The functional behavioral activities recorded included: rearing up repeatedly, moving about, provoking, climbing, grooming, yawning, rotating, smelling and vomiting. At the fourteenth day, all rats were killed after thirty minutes of nicotine injection,the brains were dissected out and the region of striatum was separated immediately. Total RNA was extracted from striatum by RNeasy Total RNA Kit. PCR amplification was performed at special condition. For semi-quantitative analysis, 10 μ L of PCR products for each was examined by electrophoresis on 12 g/L agarose gel containing 0.5 mg/L ethidium bromide,and absorbance (A value) was quantitated by using densitometric scanning imaging system, thuse D1R,D2R mRNA expression were determined. Differences between means were analyzed with two-tailed student's t test.MAIN OUTCOME MEASURFS: Changes of locomotor activities and the gene mRNA expression levels of D1 R and D2R in the regions of striatum in rats.RESULTS: Totally 24 SD rats were involved in the final results.① Locomotor activities of rats become more active after 3-day nicotine administration and reach the top during 7-14 days.②The A value of total RNA ratio of A260/A280 ＞1.8, and the total RNA had no degradation with 12 g/L agarose gels electrophoresis. ③As expected, PCR amplification product lengths of D1R, D2R,βA were 350 bp, 399 bp, 218 bp respectively. A significant increase of 23% of D1R mRNA expression in the region of striatum detected in the nicotine group compared with that of control group (98.63±1.13 and 65.29±1.45 seperately,P ＜ 0.01), no difference was detected on the level of D2R mRNA expression in the same regions above (76.73±1.45 and 78.21±1.69 respectively ,P ＞ 0.05 ).CONCLUSION: Nicotine may induce changes of locomotor activities of rats by up-regulating D1R mRNA expression in striatum.

Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function.
Epilepsy ; genetics ; Humans ; KCNQ2 Potassium Channel ; Mutation ; NAV1.1 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins ; genetics ; Potassium Channels ; genetics ; Potassium Channels, Voltage-Gated ; Receptors, Nicotinic ; genetics ; Research ; trends ; Research Design ; Sodium Channels ; genetics ; Voltage-Gated Sodium Channel beta-1 Subunit

Objective Toinvestigatetheriskfactorsforleukoaraiosis(LA)inpatientswithlarge arteryatherosclerosis(LAA).Methods Theclinicaldata(age,sex,hypertension,diabetes,smoking, serum lipid level,hyperhomocysteinemia,and numbers of stenosis or occluded cerebral arteries)of 312 patients with LAA classified by the modified stop stroke study trial of Org 10172 in acute stroke treatment (SSS-TOAST ) were analyzed retrospectively. The age-related white matter changes (age related white matter changes,ARWMC)scale was used to evaluate LA. All the 312 patients were divided into non-LA group(n=72)and LA group(n=240)according the T2 weighted magnetic resonance imaging (MRI) and fluid attenuated inversion recovery(FLAIR)sequence,and 3 groups according to the (age-related white matter changes,ARWMC)scores:mild LA,moderate LA,and severe LA groups. The patients with multiple risk factors were analyzed by the univariate and multivariate Logistic regression analyses. Results (1)Of the 312 patients with LA,227 were males (72. 8%). Their average age was 64 ± 11 years,and 240 of them (76. 9%)had LA. Multivariate Logistic regression analysis showed that age (OR,2. 911,95%CI 1. 647-5.146,P=0. 000),hypertension (OR,2. 583,95%CI 1. 373-4.857,P<0. 01),diabetes (OR,1. 882, 95%CI 1. 058-3. 348,P <0. 05),the numbers of stenosis or occlusion arteries (OR,1. 851,95%CI 1.018-3. 367,P<0. 05),and lacunar infarction (LI)(OR,1.493,95%CI 1. 202-1. 853,P<0. 01)were the risk factors for LA. (2)The comparison of the clinical data in patients with different severity in the LA group found that there were significant differences in age,hypertension,diabetes,the numbers of stenosis or occlusionarteries,andLIamongthe3groups(allP<0.05).Conclusion Age,hypertension,diabetes, the numbers of stenosis or occlusion arteries,and LI are the independent risk factors for patients with LAA,and it is associated with the severity of LA.

Objective To investigate the clinical effects of Shenlian capsule,trastuzumab combined with SOX regimen in the treatment for HER-2 positive advanced gastric carcinoma.Methods A total of 314 patients with HER-2 positive advanced gastric carcinoma in our hospital were randomly divided observation group and control group,157 cases in each group.The observation group was treated by SOX regimen and trastuzumab,while the control group was given Shenlian capsule on the base of control group.After treatment,the short-term effects in the 2 groups were evaluated.Before and after the treatment,the levels of SDF-1,CXCR4,FSP-1 and MRP-l4 in the 2 groups were detected.During the treatment,the rates of neurotoxicity,gastrointestinal reaction,liver function injury,renal function injury,rashes and bone marrow suppression were observed in the 2 groups.After the treatment,3 years follow-up was performed,the 1 year survival rate,3 year survival rate,overall survival (OS) and progression-free survival (PFS) were observed.Results After the treatment,the control rate (92.7％ vs.79.9％;Z=3.812,P=0.037) and efficiency rate (78.1％ vs.66.4％;Z=3.712,P=0.039) were significantly higher in treatment group than which in the control group (P＜0.05).After the treatment,the levels of SDF-1,CXCR4,FSP-1,MRP-14 in treatment group were significantly lower than control group (t=4.091,4.310,3.972,3.821,P＜0.05).During the treatment,the rates of neurotoxicity,gastrointestinal reaction,liver function injury,renal function injury,rashes,bone marrow suppression were significantly lower in treatment group than control group (x2=5.182,4.671,4.491,5.091,5.204,4.925,P＜0.05 or P＜0.01).After the treatment,the PFS,OS (t=3.714,3.612,P＜0.05),3 year survival rate (x2=3.105,P=0.043) were significantly higher in treatment group than the control group.Conclusions The Shenlian capsule,trastuzumab combined with SOX regimen has a good effect and low toxic effects in the treatment of HER-2 positive advanced gastric carcinoma,and they could prolong the survival time.

OBJECTIVETo study pantothenate kinase 2 (PANK2) gene mutations in Chinese patients with Hallervorden-Spatz syndrome (HSS).

METHODSPANK2 gene mutations were detected by PCR, DNA sequence analyses, restriction enzyme digestion and PCR-single strand conformation polymorphism in 5 patients, 3 unaffected family members and 51 unrelated healthy persons.

RESULTSNovel compound heterozygous PANK2 gene mutations, A803G and T1172A, in exons 3 and 5, respectively, were found in one patient. At the same time, 3 types of single nucleotide polymorphisms, -38 t>a in 5'-UTR, IVS1+42 c>a and G77C in exon 1, were confirmed; among them, -38 t>a, IVS1+42 c>a, were first reported.

CONCLUSIONPANK2 gene mutations can cause HSS in Chinese patients.

Adolescent ; Adult ; Base Sequence ; Child ; China ; DNA Mutational Analysis ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pantothenate Kinase-Associated Neurodegeneration ; genetics ; Pedigree ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Young Adult

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.