Establishment and practice of the collaborative innovation system of the national clinical research center for geriatric disorders / 中华医院管理杂志

Scientific and efficient collaborative innovation system plays a key role in driving the construction and development of national clinical medical research centers. As the entity in building the national clinical medical research center for geriatric diseases, Xiangya Hospital of Central South University has carried out the " two-in-one integration" construction of the center hospital based on the principle of " simultaneous construction of the center and the hospital" . Leveraging the research, promotion and application of key technologies for common diseases and frequently occurring diseases among the elderly, a collaborative innovation system has come into being since 2018, consisting of three organically linked platforms of technology support platform, core research platform and public service platform, as well as four support systems of collaborative innovation network support system, innovation management system support system, special innovation fund support system and innovation ability training support system. By 2021, the collaborative innovation system has been completed in general, and desirable results have been achieved in clinical research, achievements translation and technology promotion for geriatric diseases. These achievements have strongly promoted the development of China′s elderly health sector.

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.

Advances in the TAF1 gene / 中华神经科杂志

TAF1 gene encodes TATA-box binding protein-associated factor-1, which serves as a scaffold for the assembly of the transcription factor ⅡD and participates in the transcription of many genes in eukaryotic cells. Human TAF1 possesses intrinsic protein kinase activity, histone acetyltransferase activity as well as ubiquitin-activating and conjugating activity, and these activities have been mapped to different domains. Currently, TAF1 has been identified as the causative gene of X-linked dystonia-parkinsonism and X-linked mental retardation. What′s more, a series of functional analysis have demonstrated the importance of TAF1 gene in cell cycle and cell growth, and its relationship with neurodevelopment and tumorigenesis has also been reported. This review summarizes the research progress of TAF1 including structure, phenotypes and biological function.

Research progress on the association between Parkinson′s disease and inflammatory bowel disease in genetics and gut microbiota / 中华神经科杂志

Parkinson′s disease (PD) is a common degenerative disease of central nervous system. PD is closely related to gastrointestinal diseases in comorbidity studies, and the “gut brain axis” disorder may be involved in their relationship. In recent years, relevant studies have suggested that there are genetic and epidemiological evidences to link PD with inflammatory bowel disease (IBD). This article reviews the relationship between PD and IBD from the genetic evidence and the relevant concept of “gut brain axis”.

Research advances in clinical scales for essential tremor / 中华老年医学杂志

Essential tremor(ET)is one of the most common movement disorders, with a prevalence of 4.6% in people over 65 years old.Action tremor of both upper limbs at 4-12 Hz action tremor in both upper limbs is the main clinical feature of ET patients.ET was previously considered to be a benign isolated symptomatic disease, but in recent years, researches have found that ET is a family of diseases with high clinical and genetic heterogeneities.In addition to tremor, it can also be accompanied by soft neurological signs and various non-motor symptoms, leading to different degrees of function impairment in patients.Early comprehensive evaluation and long-term follow-up of patients with ET are essential.The standardized scale is the most important tool for ET assessment.This article reviews various tremor assessment scales.

Effect of CAG repeats on the age at onset of patients with spinocerebellar ataxia type 2 in China / 中南大学学报(医学版)

Objective: Spinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant ataxias in the world. Several reports revealed that CAG repeats in some polyQ-containing genes may affect the age at onset (AAO) of patients with SCA2, however, little studies were conducted among Chinese patients with SCA2. Thus, the aim of this study is to evaluate the effect of CAG repeats on the AAO of patients with SCA2 in China.Methods:A total of 119 patients with SCA2 were enrolled and were divided into 2 groups according to their major phenotype:17 patients from 9 families with Parkinson ' s syndrome were grouped as the Parkinson ' s disease-SCA2 (PD-SAC2); 91 patients from 66 SCA2 families and 11 sporadic SCA2 patients were grouped as the ataxia-SCA2 (A-SCA2). Blood samples were obtained from the subjects, and the CAG repeat length in ATXN2 and other (CAG)n-containing genes was screened using fluorescent PCR. The Spearman ' s rank correlation between the CAG repeat length in (CAG)n-containing genes and AAO was analyzed. Regression analysis was performed to investigate whether the CAG repeat length could explain the variant of AAO. A t-test was used to compare the difference of CAG repeat length in (CAG)n-containing genes between the PD-SAC2 and A-SCA2 groups. Results:The CAG repeat length in the longer allele of ATXN2 was negatively correlated with AAO of SCA2 (R=?0.251, P<0.05), and the CAG repeat length could explain 41.7％of the variation of AAO. AAO negatively correlated with the CAG repeat length in the shorter allele of ATXN7 (R=?0.251, P=0.006) or in the longer allele of TBP gene (R=?0.197, P=0.034). A tendency of delay in the AAO was also observed in patients with SCA2 carrying the CAG repeat within the ATXN3, CACNA1A, ATXN7, TBP, and RAI1. In addition, we found that the CAG repeat length in ATXN7 and ATXN2 between the A-SCA2 and the PD-SCA2 groups was significantly different (both P<0.05).Conclusion:The CAG repeat in ATXN2 is a major genetic factor for the AAO of patients with SCA2 in China. The CAG repeat length in ATXN3, CACNA1A, ATXN7, TBP, and RAI1 genes might be a potential factor associated with the AAO of SCA2. The CAG repeat in ATXN7 might be a potential factor affecting the Parkinson??s syndrome in SCA2.

Research advances in the treatment of essential tremor / 中华神经科杂志

Essential tremor (ET) is a common movement disorder. It is characterized by a distinctive 4-12 Hz action tremor typically affecting bilateral upper limbs. Existing drugs for ET mainly include β-blockers, anticonvulsants, benzodiazepines, etc. However, the efficacy of existing drugs is limited. With the development of the medical research, some progress has been made in the treatment of ET. The review will explore the recent advances in the treatment of ET,such as new drugs, surgical treatment, repetitive transcranial magnetic stimulation, rehabilitation treatment, etc., in order to provide clinical application prospects.

Research progress of somatosensory involvement in amyotrophic lateral sclerosis / 中华神经科杂志

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons selectively. Although the motor system lesion is the most predominant clinical manifestation of ALS, with the progression of the understanding of the pathogenesis and clinical detection of the disease, more and more patients are found to have extra-motor features of ALS, such as somatosensory involvement, etc. The research results demonstrated that ALS might be a kind of disorder combined with sensory disturbance according to the electrophysiology, neuropathology, neuroimaging, animal model simulation, genetic evidence, and other methods detected. We, herein, review the prevalence and detection methods especially the aspect of genetic associations implicated in the sensory nerve disturbance of ALS.

Clinical, pathologic and genetic analysis of 3 families with dystrophinopathy / 中华实用儿科临床杂志

Objective:To explore the phenotypic and genotypic characteristics of 3 Chinese families with dystrophinopathy, so as to provide the data for earlier diagnosis and therapy.Methods:The clinical, muscle pathology and electrophysiological data from the 3 families with dystrophinopathy were analyzed.The perpheral venous blood of 15 members from the 3 families was collected.Meanwhile, the known genes that were related to neuromyopathy were detected.Results:There were 8 patients in the 3 families.All the patients presented progressive weakness of extremities as the main manifestation, with elevated creatine kinase (CK) and myogenic changes in electrophysiological examination.The proband of family 1 was a 15 years old boy with 1 year history.He displayed limb weakness and accompanied with muscle pain after exercise.Muscle pathology only revealed denatured and atrophy muscle fibers, without necrosis and hyperplastic muscle fibers.The proband of family 2 was a 9 years old boy with 1 year history.His muscle pathology illustrated degeneration, necrosis, proliferation and lipid deposition muscle fibers.The proband of family 3 was a 16 years old boy with 10 years history.He exhibited generalized muscle atrophy, spine and chest deformity.His muscle pathology demonstrated classical muscular dystrophy changes.Gene detection gave information that deletion mutation in exons 45 to 47 of DMD gene in family 1 proband.c.2636 T> G mutation in exons 18 of DMD gene in family 2 proband, repeat mutation in exons 61 to 76 of DMD gene in family 3 proband; c.2636T>G was classified as pathogenic variation according to the guidelines for the interpretation of sequence variants of the American college of medical genetics and genomics guidelines. Conclusions:The phenotype of dystrophinopathy is related to genotype.A new mutation of DMD gene c. 2636T>G is discovered.Early patient with dystrophinopathy can only display pained weakness of muscle after exercise.Muscle pathology and gene detection should be performed as soon as possible.

Expert consensus on the management strategy of patients with hereditary ataxia during prevention and control of novel coronavirus pneumonia epidemic / 中华医学遗传学杂志

Since December 2019, a series of highly infectious cases of unexplained pneumonia have been discovered in Wuhan, Hubei Province, which have been confirmed as '2019 corona virus disease' caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus can invade many human systems including the lungs. Patients with central nervous system involvement may show a series of neurological symptoms, which is easy to be misdiagnosed and neglected, thereby increasing the risk of SARS-CoV-2 transmission. Hereditary ataxia is a large group of neurodegenerative diseases with great clinical and genetic heterogeneity and high mortality and disability. In view of the seriousness of the COVID-19 epidemic, a series of prevention and control measures adopted by the government have restricted the follow-up, diagnosis and treatment of patients by the hospitals, which has a great impact on their mental and physical health. In order to standardize the management of patients during the prevention and control of COVID-19 epidemic, the Specialized Committee of Neurogenetics of the Neurophysician Branch of Chinese Medical Doctor Association has formulated this consensus, with an aim to help patients to overcome the difficulties and pass the epidemic prevention period safely.

Genetic and clinical features of sorbitol dehydrogenase gene-related Charcot-Marie-Tooth disease in Chinese population / 中华神经科杂志

Objective:To report the genetic and clinical features of sorbitol dehydrogenase (SORD) gene-related Charcot-Marie-Tooth disease (CMT) in Chinese population.Methods:Fifty-seven undiagnosed sporadic or autosomal recessive (AR) inherited CMT2 families were collected from the Department of Neurology of the Third Xiangya Hospital from 2009 through 2018 .Polymerase chain reaction combined with Sanger sequencing were used to detect the mutations of SORD gene, and the relative clinical features were summarized. Results:The homozygous SORD gene hot spot mutation c.757delG (p. Ala253GlnfsTer27) was detected in four sporadic patients, accounting for about 7% of the total. Two patients with CMT2 phenotype were characterized by progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in both motor and sensory nerves. Two patients with distal hereditary motor neuropathy (dHMN) phenotype exhibited progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in motor nerves only. The age of onset was between five and 16 years, and the CMT neuropathy score was 2-9.Conclusions:The homozygous hot spot mutation of SORD gene (c.757delG, p.Ala253GlnfsTer27), and related childhood or adolescence onset, mildly affected CMT2/dHMN phenotypes are firstly reported in Chinese population. SORD gene-related CMT might be the most common subtype of AR-CMT2.

Advances in research on myoclonus-dystonia syndrome / 中华神经科杂志

Myoclonus-dystonia syndrome (MDS) is a special type of dystonia-plus syndromes. It is an autosomal-dominant movement disorder syndrome characterized by myoclonus and dystonia and accompanied by certain mental symptoms. The disorder usually occurs in childhood. Myoclonus and dystonia are usually involved in upper limbs, trunk and neck. The main pathogenic gene of MDS is ε-sarcoglycan gene (SGCE). Up to date, the mechanism that how this gene leads to the disease is not clear. The continuous progress of MDS can cause disability and bring great pain to patients and their families. In recent years, significant progress has been made in the research of this disease. This article will systematically review the pathogenesis, clinical phenotype, genetics, diagnostic criteria, differential diagnosis and treatment of MDS.

Mechanism of re-emergent tremor in Parkinson′s disease / 中华神经科杂志

Parkinson′s disease is a common degenerative disease of the central nerve system, mainly caused by the degeneration of dopaminergic neurons in the compact part of substantia nigra. Tremor is one of the most common symptoms of Parkinson′s disease. Part of patients changing posture position could cause the tremor suspended for a period of time, after that, the tremor appear again. This clinical phenomenon is characterized by the reproducibility of Parkinson′s disease tremor, called re-emergent tremor (RET). The cause of RET mechanism is still unclear and the relative researches are less. This review summarizes the possible mechanism, clinical features and significance of RET in Parkinson′s disease.

Pay attention to repeat expansion mutation related neurogenetic diseases / 中华神经科杂志

Repeat expansion diseases (REDs), which include Huntington disease, spinocerebellar ataxia and fragile X syndrome, are important part of the neurogenetic diseases. REDs are caused by expansions of sequence repeats in the human genome. The REDs spectrum expanded rapidly with the advances of technology regarding molecular genetics in recent years. Although rare, these genetic disorders can be frequently met by neurologists. This article introduces the definition, classification, diagnosis and new progresses in treatment of REDs based on the most recent research findings.

Research progress of oculomotor disorder in Parkinson's disease / 中华神经科杂志

Parkinson's disease (PD) is a common neurodegenerative disease characterized by bradykinesia,resting tremor,muscle rigidity,and abnormal gait posture.Ocular motor function test plays an important part in neurological examinations.It has been widely accepted that specific ocular motor patterns contribute to diagnosis of Parkinsonian syndrome including progressive supranuclear palsy and multiple system atrophy.However,recent studies have shown that patients of PD may also exhibit specific eye movement disorders,which will be helpful in the early diagnosis,evaluation and differential diagnosis of PD.In 2015,the Movement Disorder Society clinical diagnostic criteria for Parkinson's disease suggested that sustained staring evoked nystagmus could be used as an exclusive criterion for PD.The clinical features,detection methods and clinical significance of oculomotor dysfunction in PD are reviewed in this article.

The electrophysiological characteristics of the four most common genotypes of Charcot-Marie-Tooth disease / 中华神经科杂志

Objective To analyze the electrophysiological characteristics of Charcot-Marie-Tooth (CMT) disease 1A,1X,2A and myelin protein zero (MPZ)-related CMT in Chinese patients.Methods Baseline electrophysiological data from 36 CMT1A patients,78 CMT1X patients,31 CMT2A patients and 10 MPZ-related CMT patients in the Third Xiangya Hospital and Xiangya Hospital of Central South University during 2004-2018 were analyzed.Electrophysiological recordings were taken from the upper limbs (median nerve,ulnar nerve) and lower limbs (tibial nerve,peroneal nerve).Demyelination in different nerve segments was assessed by measurement of distal motor latency,motor nerve conduction velocity (MNCV),sensory nerve conduction velocity and F-wave latency,and calculation of conduction block,terminal latency index (TLI) and modified F ratio (MFR);Axonal degeneration was assessed by measuring compound motor action potential (CMAP) and sensory nerve action potential.The relationship between the gender,age at onset,duration,Overall Neuropathy Limitation Scale (ONLS) score and indexes of peripheral nerve electrophysiology was statistically analyzed.Results The peripheral nerves of CMT1A patients were characterized by uniform demyelination and axonal degeneration.MNCV ((21.39± 6.72) m/s) and CMAP amplitude (2.40 (3.50) mY) of median nerve of CMT1A patients were decreased.The peripheral nerves of CMT1X patients were also characterized by uniform demyelination and axonal degeneration.MNCV (35.20 (6.77) m/s) and CMAP amplitude (2.60 (3.79) mY) of median nerve of CMT1X patients were decreased.CMT2A patients showed axonal degeneration of the peripheral nerves and CMAP amplitude ((4.75 ±2.38) mV) of median nerve of CMT2A patients was decreased.The electrophysiological data in MPZ-related CMT patients demonstrated variability.The TLI and MFR for the median and ulnar nerves in these four subtypes were normal.MNCV (r=0.423,P=0.025) of median nerve in CMT1A patients was positively correlated with age at onset.MNCV (r=0.782,P=-0.013) of median nerve in MPZ-related CMT patients was positively correlated with age at onset.CMAP amplitude (r=0.652,P＜0.01) of median nerve in CMT2A patients was positively correlated with age at onset.Demyelination and axonal degeneration in male CMT1X patients were relatively more severe than those in female patients,and MNCV (Z=-3.300,P＜0.01) and CMAP amplitude (Z=-3.960,P＜0.01) of median nerve,MNCV (Z=-2.56,P=0.011) and CMAP amplitude (Z=-2.311,P=0.048) of ulnar nerve of male patients were lower than those of female patients.The ONLS score of CMT1A (r=-0.494,P＜0.01),CMT1X (r=-0.596,P＜0.01) and CMT2A patients (r=-0.494,P=0.012) was inversely associated with CMAP amplitude.Conclusions The electrophysiological characteristics of CMT1A,CMT1X,CMT2A and MPZ-related CMT are different.Electrophysiological examinations are the basis of clinical classification and could provide guidance for further genetic testing and diagnosis.CMAP amplitude may serve as an objective index to assess the severity of functional disability in CMT patients.

A review on evaluating application of abnormal iron deposition in brain on diagnosis and differential diagnosis of Parkinson's disease / 中华老年医学杂志

Parkinson's disease (PD)is a common neurological degenerative diseases,and its diagnosis mainly depends on a patient's clinical manifestations and the response to dopaminergic drugs.The coincidence rate between clinical diagnosis and pathological diagnosis for PD is only 70％-80％.It is found that abnormality of intracranial iron deposition is one of the important pathological changes in PD progression.Therefore,it can be helpful to detect the abnormal iron deposition in brain using MRI and Doppler sonography for early diagnosis and differential diagnosis of PD.

The clinical characteristics and risk factors of frozen gait in Parkinson's disease / 中国医师杂志

Objective o investigate the clinical characteristics and relevant risk factors of freezing gait in patients with Parkinson's disease (PD).Methods A total of 570 consecutive PD patients were registered basic information and evaluated by Unified Parkinson's Disease Rating Scale (UPDRS) and New Freezing of gait questionnaire (NFOG-Q).They were divided into the PD with freezing gait group (188 cases) and non-freezing gait group.Results UPDRS score in each part (UPDRS-Ⅰ,UPDRS-Ⅱ,UPDRS-Ⅲ,UPDRS-Ⅳ) and Hoehn & Yahr stage of the PD freezing gait group was significantly higher than that of the non frozen gait group (P ＜ 0.05).Conclusions PD patients with frozen gait group experience more rapid PD progression than those without freezing of gait.The appearance of FOG is associated with the mental behavior and emotion,treatment complication,disease severity,and course of PD.

Study on fatigue symptoms and related factors in Parkinson's disease patients / 中国医师杂志

Objective To investigate the prevalence of fatigue symptoms and investigate its related factors in patients with Parkinson's disease (PD).Methods The Parkinson's Fatigue Scale (PFS-16) was used to assess the fatigue status of 453 PD patients.These patients were divided into fatigue group (mean PFS-16≥3.3 defined as fatigue) and non-fatigue group.All of them completed the assessment of the relevant scale.Results Among 453 PD patients,there were 169 patients (37.3％) in fatigue group and 284 patients (62.7％) in non-fatigue group.Unified Parkinson's disease Rating Scale (UPDRS) and HoehnYahr (H-Y) staging in fatigue group were significantly higher than non-fatigue group (P ＜0.05).Motor symptoms,mental and emotional status and daily living ability are positively correlated with fatigue symptoms.Conclusions The motor symptoms and non-motor symptoms are more serious in PD patients with fatigue.The motor symptoms,mental and emotional status,daily living ability and Hoehn-Yahr (H-Y) stage are the main related factors of fatigue symptoms in PD patients.

Study on the clinical features and related factors of cognitive impairment in Parkinson's disease / 中国医师杂志

Objective To explore the correlated factors and clinical features of cognitive impariment in parkinson's disease (PD).Methods A total of 419 patients with PD were collected from Xiangya Hospital of Centre-South University during Mar 1st,2017 to Nov 30th,2017.The cognitive functions of patients were assessed with the Mini-Mental State Examination (MMSE),and the basic information and the motor symptoms of 419 PD patients were selected at the same time.The PD patients were classified into three groups according to the MMSE score:PD with no cognitive impairment (PD-NC),mild cognitive impairment in PD (PD-MCI),and Dementia in PD (PD-D).The data were analyzed by SPSS 20.0.Results There were 156 patients with PD-MCI (37.2％) and 64 patients with PD-D (15.3％).The difference of sex and disease duration among three groups were not statistically significant (P ＞ 0.05).The significant difference was found among PD-D,PD-MCI,and PD-NC groups in age of onset,age,educational attainment,Unified Parkinson's disease Rating Scale (UPDRS)-Ⅱ score,UPDRS-Ⅲ score and Hoehn-Yahr stage (P ＜ 0.05).There were significant differences among three groups in MMSE score and its items (P ＜ 0.01).Logistics regression analysis found that the age of onset,educational attainment,and Hoehn-Yahr stage were the risk factors of cognitive impairment in PD patients (P ＜ 0.05).Conclusions Cognitive impairment is common in PD patients,and it is relevant to the age of onset,educational attainment and the severity of illness of PD patients.