Research progress of clinical subtypes of Parkinson′s disease / 中华神经科杂志

Parkinson′s disease (PD) is a widely heterogeneous disorder with a broad list of motor and nonmotor manifestations. PD varies in clinical features, dominant symptoms, and rate of progression from case to case, suggesting the existence of distinct subtypes. Research on PD subtypes aims to understand this heterogeneity. This review summarized the commonly used PD subtyping solutions and discussed the challenges and future perspectives of subtyping. In future study, by designing a more standardized research and comparing the differences of these subtypes in terms of a number of putative biomarkers, that might help to better understand the underlying disease mechanisms, predict prognosis, and eventually design more efficient personalized management strategies.

The phenotypic and genetic spectrum of colony-stimulating factor 1 receptor gene-related leukoencephalopathy in China / 中华神经科杂志

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.

Vascular parkinsonism revisiting / 中华神经科杂志

Vascular parkinsonism (VP) is a parkinsonism syndrome secondary to cerebrovascular damage. At present, domestic clinicians lack of understanding and pay little attention to it. This article briefly summarizes the epidemiology, etiology and pathogenesis, clinical manifestations, auxiliary examination, diagnosis and differential diagnosis, treatment and prevention of VP, for providing references to clinicians and specialists.

Advances in the study of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in Parkinson′s disease / 中华神经科杂志

Parkinson′s disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra. While the etiology of PD is likely multifactorial, and the neuroinflammation is a significant component to the pathogenesis of the disease. The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes are multiprotein innate immune complexes regulating inflammation. In the neuroinflammation of PD, the assembly of NLRP3 inflammasome complexes could recruit and activate the caspase-1. Activated caspase-1 cleaves the precursors of interleukin-1β as well as interleukin-18 to produce the downstream inflammatory cascade damaging the dopaminergic neuron. This review provides an overview of the recent studies concerning NLRP3 inflammasome in the pathophysiology of PD, and discusses potential therapeutic strategies to alleviate the progression of PD by inhibiting NLRP3 inflammasome.

Advances in the study of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in Parkinson's disease / 中华神经科杂志

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra.While the etiology of PD is likely multifactorial,and the neuroinflammation is a significant component to the pathogenesis of the disease.The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes are multiprotein innate immune complexes regulating inflammation.In the neuroinflammation of PD,the assembly of NLRP3 inflammasome complexes could recruit and activate the caspase-1.Activated caspase-1 cleaves the precursors of interleukin-1β as well as interleukin-18 to produce the downstream inflammatory cascade damaging the dopaminergic neuron.This review provides an overview of the recent studies concerning NLRP3 inflammasome in the pathophysiology of PD,and discusses potential therapeutic strategies to alleviate the progression of PD by inhibiting NLRP3 inflammasome.

Rhabdomyolysis complicated by posterior reversible encephalopathy / 中华神经科杂志

Posterior reversible encephalopathy syndrome is a clinical and radiological entity,caused by a variety of reasons.We report a case of rhabdomyolysis complicated by posterior reversible encephalopathy and suggest that giving fluids early,use of diuretics and alkalization of urine may be reasonable for patients with rhabdomyolysis.Monitoring blood pressure is noteworthy to prevent target organ damage,and if patient condition steadily deteriorates,hemodialysis should be initiated.

Analysis of cognitive function and blood glucose level in patients with Parkinson disease / 中国神经精神疾病杂志

Objective To study the relationship between level of plasma glucose and cognitive function in patients with Parkinson's disease.Methods Two hundred PD patients were assessed cognitive function using Mini-Mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Wechsler Intelligence Scale and Wechsler Memory Scale.The patients were divided into cognitive normal group (n=91) and cognitive impairment group (n=109).One hundred twenty-six normal subjects were enrolled as control group (n=126).The levels of fasting plasma glucose (FPG),postprandial plasma glucose (2hPPG),glycosylated hemoglobin (HbAlc) and the prevalence of diabetes mellitus were compared among the groups.The effect of blood glucose level on the cognitive function of PD patients was analyzed by Binary Logistic Regression.Results The levels of FPG,HbAlc and the prevalence of diabetes mellitus [5.19 (0.72),5.7％ (0.5％),14％] were significantly higher than those in the normal control group [4.85(0.79),5.6％ (0.5％),6％] (P＜0.05).The levels of FPG in PD patients with cognitive impairment [5.21 (1.32)] was significantly higher than that in PD patients with cognitive normal group [4.81 (0.95)] (P＜0.05).Although 2hPPG and HbAlc increased slightly in PD patients with cognitive impairment,the difference did not reach an significant level (P＞0.05).Binary Logistic Regression analysis showed that FPG(OR:1.764;95％ CI:0.06-3.244;P=0.068) was not associated with the impaired cognitive function in PD patients.Conclusion The present study has not revealed an association between the incidence of cognitive impairment in patients with PD and plasma glucose level although high plasma glucose may be a high risk factor for PD patients.

Analysis of risk factors for leukoaraiosis in patients with large artery atherosclerosis / 中国脑血管病杂志

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.

A cross-sectional study on the association between platelet-activating factor acetylhydrolase gene polymor-phism and cerebral artery atherosclerotic stenosis / 中国神经精神疾病杂志

Objective To investigate the relationship between platelet-activating factor acetylhydrolase gene Arg92His(4, 275; G→A), Ile198Thr(7, 593; T→C) and Val279Phe(9, 994; G→T) mutation and cerebral artery athero-sclerosis stenosis. Methods Six hundred forty-twopatients with cerebral infarction underwent cerebral digital subtrac-tion angiography (DSA).The patients were then divided into cerebral artery atherosclerosis stenosis (CAAS) group(n=477) and control group(n=81) accroding to the site and severity of their cerebral artery stenosis. Furthermore, the CAAS group were divided into intracranial artery stenosis(ICAS) subgroup(n=251), extracranial artery stenosis(ECAS) subgroup (n=115) and extracranial-intracerebral artery stenosis(ECAS) subgroup(n=111). The distributions of genotype and allele frequencies of Arg92His,Ile198Thr and Val279Phe mutation of platelet-activating factor acetylhydrolase gene were ex-amined and comparied in different groups. Results There were significant differences in the distributions of genotype and allele of Arg92His mutation between ICAS subgroup and control group(42.6% vs. 30.3%;23.3% vs. 16.4%, P 0.05). The distributions of genotype and allele of Arg92His, Ile198Thr and Val279Phe mutation were no significantly difference between CAAS group and control group (P >0.05). Conclusions Arg92His mutation may be associated with intracranial artery atherosclerotic stenosis.

Distribution of CAG repeat number within androgen receptor gene in Chinese Han nationality and its application in genetic diagnosis for Kennedy's disease / 中华老年医学杂志

Objective To investigate the distribution of androgen receptor (AR) gene CAGrepeats in the Chinese Han nationality and its application in genetic diagnosis for Kennedy's disease (KD). MethodsRT-PCR,denaturing polyacrylamide gel electrophoresis (DPAGE) and gene sequencing were conducted for AR gene CAG repetition among 100 healthy controls and 28 patients diagnosed as motorneuron diseases,and the number of the repetition was counted. Results The healthy controls had a range of 15-31 times of CAG repetition,with an average of (23 ± 3) times.Among patients with motoneuron disease,3 cases with CAG repetition for more than 40 times (namely,46,47 and 47 times) were diagnosed as KD.The main clinical manifestations included slow progress of limb weakness,primarily in the proximal lower limbs,fatigue accompanied by myalgia,muscle jumping,muscle atrophy,elevated serum creatine kinase (CK) levels,neurogenic damage revealed by electromyogram (EMG) and androgen insensitivity.Conclusions The incidence of KDmay be underestimated in the Chinese population.Performing genetic diagnosis in patients with motor neuron disease for AR gene can improve clinical diagnosis and avoid misdiagnosis.

Construction of pcDNA3.1-myc/PINK1 and its expression in COS-7 cells / 中国医师杂志

Objective To construct eukaryotic expression vector of PINK1 (pcDNA3. 1-myc/PINK1) and verify PINK1 expression in pcDNA3.1-myc/PINK1 transfected COS-7 cells. Methods The cDNA fragment encoding human PINK1 gene was amplified by PCR method from human cDNA library. After nucleotide sequencing, this cDNA fragment was inserted into an eukaryotic expression vector pcDNA3. 1-myc-his( - )B using gene cloning and DNA recombination. The recombinant was then transferred into COS-7 cells by liposome. The expression of the target molecule was assayed by western blotting. Results The sequence of DNA fragment amplified by PCR was consistent with that published in Genbank, and digestion of the recombinant plasmid with EcoR Iand BamH Iliberated DNA fragments with expected size. PINK1 was expressed and synthesized in transfected cells after 48h culture. Conclusion An eukaryotic expression plasmid containing human PINK1 gene was successfully constructed, and it can express out objective protein, which has laid a concrete foundation for future study on PINK1.

Chronic nicotine induces the changes of locomotor activities in rats by increasing the mRNA levels of dopamine D1 receptor in striatum / 中国组织工程研究

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.

Studies on PANK2 gene mutations in Chinese patients with Hallervorden-Spatz syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study pantothenate kinase 2 (PANK2) gene mutations in Chinese patients with Hallervorden-Spatz syndrome (HSS).</p><p><b>METHODS</b>PANK2 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.</p><p><b>RESULTS</b>Novel 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.</p><p><b>CONCLUSION</b>PANK2 gene mutations can cause HSS in Chinese patients.</p>

Progress in molecular genetics of epilepsy / 中华医学遗传学杂志

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.

Clinical features of autosomal recessive juvenile Parkinson disease / 临床神经病学杂志

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

Clinical features of juvenile Parkinson's disease / 临床神经病学杂志

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.

Analysis of the clinical features and genetic mutation of spinocerebellar ataxia type 6 from Chinese kindreds / 临床神经病学杂志

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.