Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying A...Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying AIMDs using a genome-wide association study(GWAS).Methods:GWASs on AIMDs were conducted in three independent cohorts:a discovery cohort of 3067 patients(2016 subjects were reserved after quality control),a validation cohort of 277 patients,and a multi-ancestry validation cohort of 766 patients.Subsequent post-GWAS analyses included gene-based analyses,transcriptome-wide association studies(TWASs),and polygenic risk score(PRS)profiling.Results:Our study identified two loci located in RAB44 gene(rs116249243,P=5.98×10^(-9);rs117097482,P=1.17×10^(-8))associated with extrapyramidal symptoms(EPSs),1 locus(rs6826172,P=5.56×10^(-9))related to akathisia,and 76 loci linked to involuntary movements(11 genes were mapped).Risk loci located in CNTNAP2,LUZP2,TMEM167A,and RAB44 genes were successfully replicated in the validation cohort,whereas the locus located in RAB44 was also replicated in the multi-ancestry cohort.Gene-based analyses indicated that XRCC4 and PAIP2B reached significance at the genome-wide level in involuntary movements.Tissue expression analysis revealed that involuntary movement-related genes are predominantly expressed in the substantia nigra.Additionally,the TWAS suggested a causal relationship between XRCC4 and involuntary movement.The PRSs derived from the discovery cohort significantly predicted AIMDs in the validation cohort,with area under the receiver operating characteristic curve(AUC)values from 0.60 to 0.80.Conclusions:Our findings highlight the role of substantia nigra related gene polymorphisms in AIMDs.This study provides novel insights into the pathogenesis of AIMDs and supports the potential for personalized treatment approaches for schizophrenia.展开更多
Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),a...Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),and serve as evidence-based augmenters in treatment-resistant depression.Nonetheless,acute antipsychotic-induced movement disorders(AIMDs)[extrapyramidal symptoms(EPS)]are common and clinically costly,impairing quality of life,adherence,and outcomes.The acute spectrum is dominated by dystonia(sustained,often painful contractions).展开更多
Limb movement disorder after stroke is one of the main causes of disability,seriously affecting patients’quality of life.Although modern medical treatment can alleviate some symptoms,it has limitations.Traditional Ch...Limb movement disorder after stroke is one of the main causes of disability,seriously affecting patients’quality of life.Although modern medical treatment can alleviate some symptoms,it has limitations.Traditional Chinese medicine,with an overall perspective and syndrome differentiation and treatment as its core,intervenes in the disease through various therapies,such as acupuncture,Chinese herbal medicine,Tuina massage,and traditional exercise,demonstrating unique advantages.This article reviews the understanding of the etiology and pathogenesis of limb movement disorders after stroke in traditional Chinese medicine,systematically summarizes the clinical application and research progress of main treatment methods such as acupuncture,Chinese herbal medicine,and Tuina massage,analyzes the problems existing in current research,and looks forward to future development directions,aiming to provide references for clinical treatment.展开更多
Objective To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disord...Objective To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as sia-lorrhea and hyperhidrosis. Methods A retrospective study of BTX-B injections in treatment of 58 patients with various neurological disorders was performed. The mean follow-up time was 0.9 ± 0.8 years. Results of the first and last treatment of patients with at least 3 injection sessions were compared. Results The response of 58 patients to a total of 157 BTX-B treatment sessions was analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in moderate or marked improvement while 17 sessions (10.8%) had no response. The clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41 patients with at least 3 injection ses-sions (mean 10 ± 8.6), most patients needed increased dosage upon the last session compared to the first session. Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with BTX-B treatment. Conclusions Though most patients require increased dosage to maintain effective response after repeated injections, BTX-B is an effective and safe treatment drug for a variety of movement disorders, as well as drooling and hyperhidrosis.展开更多
Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific cir...Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and D2). Single photon emission computerized tomography (SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington’s disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette’s syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson’s disease (PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.展开更多
BACKGROUND The psychological state of patients with post stroke limb movement disorders undergoes a series of changes that affect rehabilitation training and recovery of limb motor function.AIM To determine the correl...BACKGROUND The psychological state of patients with post stroke limb movement disorders undergoes a series of changes that affect rehabilitation training and recovery of limb motor function.AIM To determine the correlation between motor rehabilitation and the psychological state of patients with limb movement disorders after stroke.METHODS Eighty patients with upper and lower limb dysfunction post stroke were retrospectively enrolled in our study.Based on Hospital Anxiety and Depression Scale(HADS)scores measured before rehabilitation,patients with HADS scores≥8 were divided into the psychological group;otherwise,the patients were included in the normal group.Motor function and daily living abilities were compared between the normal and psychological groups.Correlations between the motor function and psychological status of patients,and between daily living ability and psychological status of patients were analyzed.RESULTS After 1,2,and 3 wk of rehabilitation,both the Fugl-Meyer assessment and Barthel index scores improved compared to their respective baseline scores(P<0.05).A greater degree of improvement was observed in the normal group compared to the psychological group(P<0.05).There was a negative correlation between negative emotions and limb rehabilitation(-0.592≤r≤-0.233,P<0.05),and between negative emotions and daily living ability(-0.395≤r≤-0.199,P<0.05).CONCLUSION There is a strong correlation between motor rehabilitation and the psychological state of patients with post stroke limb movement disorders.The higher the negative emotions,the worse the rehabilitation effect.展开更多
Background Vocal cord movement disorder （VCMD） is a laryngeal disorder characterized by paradoxical adduction of the vocal cords during in inspiration, expiration or both. The nursing experience of patients with VCM...Background Vocal cord movement disorder （VCMD） is a laryngeal disorder characterized by paradoxical adduction of the vocal cords during in inspiration, expiration or both. The nursing experience of patients with VCMD after aortic dissection surgery is limited. Methods We retrospectively analyzed the clinical data and nursing records of 269 patients after aortic dissection surgery in Guangdong General Hospital between May 2010 and May 2012. We observed the patients＇ pronunciation, and judged if there was dysphagia undergoing water drinking test two hours after extubation, to confirm whether patients had VCMD. Results Seventeen patients had VCMD after aortic dissection surgery, of whom 2 suffered hoarseness, 3 had dysphasia and 12 had both hoarseness and dysphasia. After timely treatment and carefully nursing, all the patients recovered well. Conclusions With the enhanced care of patients with aortic dissection, observing hoarseness appearance and drinking experiment immediately after extubation can detect VCMD as soon as possible. Further rehabilita- tion training and psychology care can prevent bucking and aspiration effectively, and promoting recovery and improving patient＇s life quality.展开更多
BACKGROUND Spinal anesthesia is commonly used for various surgeries.While many complications occur after induction of spinal anesthesia,involuntary movement is an extremely rare complication.CASE SUMMARY Herein,we rep...BACKGROUND Spinal anesthesia is commonly used for various surgeries.While many complications occur after induction of spinal anesthesia,involuntary movement is an extremely rare complication.CASE SUMMARY Herein,we report the case of a 54-year-old healthy male patient who experienced involuntary movements after intrathecal injection of local anesthetics.This patient had undergone metal implant removal surgery in both the lower extremities;7 h after intrathecal hyperbaric bupivacaine administration,involuntary raising of the left leg began to occur every 2 min.When the movement disorder appeared,the patient was conscious and cooperative.No other specific symptoms were noted in the physical examination conducted immediately after the involuntary leg raising started;moreover,the patient's motor and sensory assessments were normal.The symptom gradually subsided.Twelve hours after the symptom first occurred,its frequency decreased to approximately once every three hours.Two days postoperatively,the symptoms had completely disappeared without intervention.CONCLUSION Anesthesiologists should be aware that movement disorders can occur after spinal anesthesia and be able to identify the cause,such as electrolyte imbalance or epilepsy,since immediate action may be required for treatment.Furthermore,it is crucial to know that involuntary movement that develop following spinal anesthesia is mostly self-limiting and may not require additional costly examinations.展开更多
AIM:To investigate whether an association exists between sleep-associated movement disorders and cardiovascular disease(CVD).METHODS:Several studies have observed the relationship of sleep-associated movement disorder...AIM:To investigate whether an association exists between sleep-associated movement disorders and cardiovascular disease(CVD).METHODS:Several studies have observed the relationship of sleep-associated movement disorders such as restless legs syndrome(RLS)and periodic limb movements during sleep with CVD,but the results were still contradictory.We performed an extensive literature search on Pub Med,Medline and Web of Science published from inception to December 2014.Additional studies were manually searched from bibliographies of retrieved studies.Meta-analyses were conducted with Stata version 12.0(Stata Corp,College Station,Texas).Pooled odds ratios(ORs)and 95%CIs were calculated to assess the strength of association using the random effects model.Sensitivity and subgroup analyses were performed to explore the underlying sources of heterogeneity.The publication bias was detected using Egger’s test and Begg’s test.RESULTS:A total of 781 unique citations were indentified from electronic databases and 13 articles in English were finally selected.Among these studies,nine are cohort studies;two are case-control studies;and two are cross-sectional studies.The results showed that the summary OR of CVD associated with sleepassociated movement was 1.51(95%CI:1.29-1.77)in a random-effects model.There was significant heterogeneity between individual studies(P for heterogeneity=0.005,I2=57.6%).Further analysis revealed that a large-scale cohort study may account for this heterogeneity.A significant association was also found between RLS and CVD(OR=1.54,95%CI:1.24-1.92).In a fixed-effects model,we determined a significant relationship between sleep-associatedmovement disorders and coronary artery disease(CAD)(OR=1.34,95%CI:1.16-1.54;P for heterogeneity=0.210;I2=30.0%).Our meta-analysis suggests that sleep-associated movement disorders are associated with prevalence of CVD and CAD.CONCLUSION:This finding indicates that sleep-associated movement disorders may prove to be predictive of underlying CVD.展开更多
BACKGROUND Dystonic gait(DG) is one of clinical symptoms associated with functional dystonia in the functional movement disorders(FMDs). Dystonia is often initiated or worsened by voluntary action and associated with ...BACKGROUND Dystonic gait(DG) is one of clinical symptoms associated with functional dystonia in the functional movement disorders(FMDs). Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. There is no report for DG in FMDs caused by an abnormal pattern in the ankle muscle recruitment strategy during gait.CASE SUMMARY A 52-year-old male patient presented with persistent limping gait. When we requested him to do dorsiflexion and plantar flexion of his ankle in the standing and seating positions, we didn’t see any abnormality. However, we could see the DG during the gait. There were no evidences of common peroneal neuropathy and L5 radiculopathy in the electrodiagnostic study. Magnetic resonance imaging of the lumbar spine, lower leg, and brain had no definite finding. No specific finding was seen in the neurologic examination. For further evaluation, a wireless surface electromyography(EMG) was performed. During the gait, EMG amplitude of left medial and lateral gastrocnemius(GCM) muscles was larger than right medial and lateral GCM muscles. When we analyzed EMG signals for each muscle, there were EMG bursts of double-contraction in the left medial and lateral GCM muscles, while EMG analysis of right medial and lateral GCM muscles noted regular bursts of single contraction. We could find a cause of DG in FMDs.CONCLUSION We report an importance of a wireless surface EMG, in which other examination didn’t reveal the cause of DG in FMDs.展开更多
Background Sleep-related movement disorders(SRMDs),such as restless legs syndrome(RLS)and periodic limb movement disorder(PLMD),are common in pediatric sleep practice.There is increasing literature on RLS,PLMD,and a n...Background Sleep-related movement disorders(SRMDs),such as restless legs syndrome(RLS)and periodic limb movement disorder(PLMD),are common in pediatric sleep practice.There is increasing literature on RLS,PLMD,and a newly described sleep disorder called“restless sleep disorder(RSD)”.We aimed to review and provide recent updates on SRMDs.Data sources A comprehensive search for relevant English-language peer-reviewed publications focused on three common SRMDs,namely,RLS,PLMD and RSD,in a variety of indices in PubMed and SCOPUS.Both relevant databases and systematic reviews are included.Results SRMDs,especially RLS and PLMD,are common in children and adolescents.However,they are underrecognized.Genetics,abnormal dopaminergic functions,and iron deficiency are the main pathophysiologies of RLS and PLMD.RLS and RSD may share common pathophysiologic mechanisms,as evidenced by low iron stores in both conditions.The diagnoses of RLS,PLMD,and RSD require specific clinical criteria and polysomnographic features.Several comorbid conditions have been associated with RLS,PLMD,and RSD.Iron therapy has been shown to be effective for treating RLS,PLMD,and RSD.There is increasing evidence on the effectiveness of specific medications in children with RLS and PLMD,but the data are still limited.Conclusions This review summarizes the pathophysiology,clinical manifestations,diagnostic criteria,and management of RLS,PLMD,and RSD in children based on relevant and recent literature.It is important for pediatricians to recognize the clinical presentation of RLS,PLMD,and RSD to facilitate early diagnosis.Further studies are needed to examine the pathogenesis,long-term consequences,and pharmacologic therapy of RSD in children.展开更多
Movement disorder management and therapy are rapidly evolving,owing to an ever-deeper understanding of disease biology and the discovery of new tools for diagnosis and treatment.With this narrative review,we aim to ex...Movement disorder management and therapy are rapidly evolving,owing to an ever-deeper understanding of disease biology and the discovery of new tools for diagnosis and treatment.With this narrative review,we aim to explore emerging therapeutic approaches for movement disorders,with a focus on Parkinson's disease(PD)and other movement-related pathological conditions,including Huntington's disease(HD),essential tremor(ET),and dystonia.This review encompasses preclinical research and human trials,providing a comprehensive overview of the current landscape.Several promising therapeutic strategies have emerged,particularly in the realm of precision medicine for PD associated with GBA and LRRK2 gene mutations.Additionally,innovative immunotherapies and drugs targeting misfoldedα-synuclein are under investigation.These approaches have the potential to influence disease progression and improve patient outcomes.The landscape of pharmacological treatments for movement disorders is both complex and diverse,with substantial progress made over the years.While current treatments effectively manage motor symptoms,they fall short of providing a definitive cure and are limited by nonmotor symptoms and potential side effects.Novel techniques,such as gene therapy,stem cell therapy,and infusion therapies,offer promising avenues for future research.展开更多
Electrical stimulation has been used to influence the nervous system since ancient times,with early examples including the Egyptian use of electric fish for pain relief.The use of electrical stimulation to improve the...Electrical stimulation has been used to influence the nervous system since ancient times,with early examples including the Egyptian use of electric fish for pain relief.The use of electrical stimulation to improve the understanding of brain regions and their functions advanced significantly in the 19th century,with experiments by Fritsch,Hitzig,and Bartholow,culminating in the development of techniques such as electrocorticography by Horsley.The field evolved with the development of stereotactic surgery in the 20th century,which allowed for the precise targeting of brain regions to treat movement disorders and chronic pain.Despite the advent of pharmacological treatments such as levodopa for Parkinson’s disease,surgical approaches such as thalamotomy and deep brain stimulation(DBS)remain crucial for patients who are unresponsive to medication.The refinement of DBS,particularly targeting the thalamus and subthalamic nucleus,has revolutionized the treatment of movement disorders and resulted in the widespread adoption of this technique.In contrast,early psychiatric treatments were typically rudimentary and driven by the dire conditions of mental asylums rather than scientific understanding.DBS has also been extended to the treatment of psychiatric disorders.Early studies conducted in the late 1990s and the early 2000s showed promising results for conditions such as obsessive-compulsive disorder.However,evidence of its efficacy in psychiatric conditions remains mixed,and ongoing research is required to establish its role.Ethical considerations are of paramount importance in this field,particularly concerning the safety,informed consent,and long-term effects of DBS.In contrast to movement disorders,psychiatric conditions experience challenges such as unclear biomarkers,subjective diagnoses,and unpredictable treatment responses,rendering DBS development in this area more complicated.展开更多
Genetic developmental and epileptic encephalopathies(DEE)are often associated with movement disorders.Accurate identification and classification of movement disorders are essential for management of these diseases.In ...Genetic developmental and epileptic encephalopathies(DEE)are often associated with movement disorders.Accurate identification and classification of movement disorders are essential for management of these diseases.In this review,we describe the characteristics of various movement disorders associated with DEE and summarize the distribution of common DEE-related gene mutations reported in previous studies,aiming to provide references for the diagnosis and treatment of these disorders.展开更多
Background:Parkinson’s Disease(PD)is characterized by motor and non‐motor symptoms that can overlap with other movement disorders,complicating accurate diagnosis and monitoring.Wearable technologies,such as smartwat...Background:Parkinson’s Disease(PD)is characterized by motor and non‐motor symptoms that can overlap with other movement disorders,complicating accurate diagnosis and monitoring.Wearable technologies,such as smartwatches,offer continuous and objective assessment of motor function,but their clinical utility in multiclass classification and symptom prediction remains underexplored.This study aimed to determine whether smartwatch‐derived motor features can distinguish idiopathic PD from other movement disorders and whether motor variability is associated with non‐motor symptom burden in PD.Methods:We analyzed data from the Parkinson’s Disease Smartwatch(PADS)dataset(N=469),which includes accelerometer and gyroscope signals recorded during 20 standardized motor tasks.For each participant,mean and standard deviation values for each axis were averaged across tasks.Diagnostic group classification was assessed using multinomial logistic regression.Among individuals with idiopathic PD(n=276),linear regression evaluated associations between motor variability and total non‐motor symptom scores from a 30‐item questionnaire.Results:Motor variability features,particularly accelerometer Y‐axis and gyroscope X‐axis standard deviations,significantly differentiated diagnostic groups(pseudo R2=0.068).Age,sex,and handedness also contributed.In the PD subgroup,higher accelerometer X and gyroscope X variability were associated with greater non‐motor symptom burden,while greater stability in the mediolateral(Y)axis was linked to fewer symptoms(adjusted R2=0.0081,p<0.001).Conclusion:Smartwatch‐derived motor variability features can modestly differentiate movement disorder diagnoses and are associated with non‐motor symptom severity in PD.Our findings support the complementary use of wearable sensors in clinical assessment and remote monitoring.Our findings also lay the foundation for future integration of wearable‐derived data into telemedicine workflows.展开更多
Background:Reports evaluating the efficacy of transcranial sonography(TCS)for the differential diagnosis of Parkinson disease(PD)and other movement disorders in China are scarce.Therefore,this study aimed to assess th...Background:Reports evaluating the efficacy of transcranial sonography(TCS)for the differential diagnosis of Parkinson disease(PD)and other movement disorders in China are scarce.Therefore,this study aimed to assess the application of TCS for the differential diagnosis of PD,multiple system atrophy(MSA),progressive supranuclear palsy(PSP),and essential tremor(ET)in Chinese individuals.Methods:From 2017 to 2019,500 inpatients treated at the Department of Dyskinesia,Beijing Tiantan Hospital,Capital Medical University underwent routine transcranial ultrasound examination.The cross-sections at the midbrain and thalamus levels were scanned,and the incidence rates of substantia nigra(SN)positivity and the incidence rates of lenticular hyperechoic area were recorded.The echo of the SN was manually measured.Results:Of the 500 patients,125 were excluded due to poor signal in temporal window sound transmission.Among the 375 individuals with good temporal window sound transmission,200 were diagnosed with PD,90 with ET,50 with MSA,and 35 with PSP.The incidence rates of SN positivity differed significantly among the four patient groups(χ^(2)=121.061,P<0.001).Between-group comparisons were performed,and the PD group showed a higher SN positivity rate than the ET(χ^(2)=94.898,P<0.017),MSA(χ^(2)=57.619,P<0.017),and PSP(χ^(2)=37.687,P<0.017)groups.SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases,collectively or individually.The incidences of lenticular hyperechoic area significantly differed among the four patient groups(χ^(2)=38.904,P<0.001).Next,between-group comparisons were performed.The lenticular hyperechoic area was higher in the PD group than in the ET(χ^(2)=6.714,P<0.017)and MSA(χ^(2)=18.680,P<0.017)groups but lower than that in the PSP group(χ^(2)=0.679,P>0.017).Conclusion:SN positivity could effectively differentiate PD from ET,PSP,and MSA in a Chinese population.展开更多
Background:RHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64),which is characterized by epilepsy,developmental delay,microcephaly,unspecific facial dysmorphism,and paroxysmal movemen...Background:RHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64),which is characterized by epilepsy,developmental delay,microcephaly,unspecific facial dysmorphism,and paroxysmal movement disorders.Most previous studies showed that the phenotypes of RHOBTB2 gene include developmental and epileptic encephalopathy(DEE)and DEE with paroxysmal movement disorders.Only one study showed that patient with RHOBTB2 variant had paroxysmal movement disorders with no epilepsy.Case presentations:Two cases with RHOBTB2 variants are presented here:Case one was diagnosed as DEE,he had recurrent afebrile focal status epilepticus and paroxysmal extrapyramidal symptoms in infancy.Interictal electroencephalogram(EEG)showed focal discharges.Brain magnetic resonance imaging(MRI)showed cortical dysplasia.Epilepsy of case one was refractory.Nevertheless,case two only showed paroxysmal movement disorders alone in adolescence.Video EEG showed focal discharges during an interictal dystonic episode and he brain MRI was normal.Conclusion:The phenotypes of RHOBTB2 gene include DEE,paroxysmal movement disorders,and DEE with paroxysmal movement disorders.RHOBTB2 can be one of the pathogenic genes of paroxysmal movement disorders.展开更多
Previous reports on the pathogenesis of age-related movement disorders,such as Parkinson’s disease(PD)and essential tremor(ET),have demonstrated the potential implications of LINGO1(leucine-rich repeat and immunoglob...Previous reports on the pathogenesis of age-related movement disorders,such as Parkinson’s disease(PD)and essential tremor(ET),have demonstrated the potential implications of LINGO1(leucine-rich repeat and immunoglobulin domain-containing protein)gene.Although LINGO2 has a high degree of homology with LINGO1,but it is less characterized and the role of LINGO2 in the development of PD/ET remains unreported.Hence,this metaanalysis was conducted to evaluate the role of LINGO2 in PD/ET pathogenesis.A total of 4 studies,which complied with the Hardy-Weinberg equilibrium,were included in the meta-analysis.Analysis of the pooled odds ratio and confidence interval of the studies were performed for five genetic models,namely:allelic,dominant,recessive,homozygous,and heterozygous.No significant association was observed between the LINGO2 polymorphism and PD/ET,although subgroup analysis through conventional metaanalysis indicated that the recessive models of rs7033345 and rs10812774 are significantly associated with predisposition to ET in the Asian population.However,trial sequential analyses for both polymorphisms were unlikely to reveal any robust effect.Hence,studies with larger samples on this association are needed in the future to corroborate our results.展开更多
Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize...Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.展开更多
α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
基金supported by the National Natural Science Foundation of China(82330042,82441005 and 82301687)the National Key R&D Program of China(2023YFE0119400)+9 种基金the Capital’s Funds for Health Improvement and Research(2024-1-4111)the STI2030-Major Projects-2021ZD0200702Fundamental Research Funds for the Central Universities(Peking University Medicine Fund for world’s leading discipline or discipline cluster development,BMU2022DJXK007)the Beijing Municipal Health Commission Research Ward Programme(3rd batch)Beijing Nova Program(20230484425)the Beijing Municipal Science&Technology Commission,Administrative Commission of Zhongguancun Science Park(Z221100003522010)the China Postdoctoral Science Foundation(2024M760141 and 2022M720302)the National Postdoctoral Program for Innovative Talents(BX20240029)the Beijing Natural Science Foundation(7254462)the Peking University Medicine Sailing Program for Young Scholars’Scientific&Technological Innovation,the Fundamental Research Funds for the Central Universities(BMU2025YFJHPY044 and BMU2025YFJHPY046).
文摘Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying AIMDs using a genome-wide association study(GWAS).Methods:GWASs on AIMDs were conducted in three independent cohorts:a discovery cohort of 3067 patients(2016 subjects were reserved after quality control),a validation cohort of 277 patients,and a multi-ancestry validation cohort of 766 patients.Subsequent post-GWAS analyses included gene-based analyses,transcriptome-wide association studies(TWASs),and polygenic risk score(PRS)profiling.Results:Our study identified two loci located in RAB44 gene(rs116249243,P=5.98×10^(-9);rs117097482,P=1.17×10^(-8))associated with extrapyramidal symptoms(EPSs),1 locus(rs6826172,P=5.56×10^(-9))related to akathisia,and 76 loci linked to involuntary movements(11 genes were mapped).Risk loci located in CNTNAP2,LUZP2,TMEM167A,and RAB44 genes were successfully replicated in the validation cohort,whereas the locus located in RAB44 was also replicated in the multi-ancestry cohort.Gene-based analyses indicated that XRCC4 and PAIP2B reached significance at the genome-wide level in involuntary movements.Tissue expression analysis revealed that involuntary movement-related genes are predominantly expressed in the substantia nigra.Additionally,the TWAS suggested a causal relationship between XRCC4 and involuntary movement.The PRSs derived from the discovery cohort significantly predicted AIMDs in the validation cohort,with area under the receiver operating characteristic curve(AUC)values from 0.60 to 0.80.Conclusions:Our findings highlight the role of substantia nigra related gene polymorphisms in AIMDs.This study provides novel insights into the pathogenesis of AIMDs and supports the potential for personalized treatment approaches for schizophrenia.
文摘Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),and serve as evidence-based augmenters in treatment-resistant depression.Nonetheless,acute antipsychotic-induced movement disorders(AIMDs)[extrapyramidal symptoms(EPS)]are common and clinically costly,impairing quality of life,adherence,and outcomes.The acute spectrum is dominated by dystonia(sustained,often painful contractions).
文摘Limb movement disorder after stroke is one of the main causes of disability,seriously affecting patients’quality of life.Although modern medical treatment can alleviate some symptoms,it has limitations.Traditional Chinese medicine,with an overall perspective and syndrome differentiation and treatment as its core,intervenes in the disease through various therapies,such as acupuncture,Chinese herbal medicine,Tuina massage,and traditional exercise,demonstrating unique advantages.This article reviews the understanding of the etiology and pathogenesis of limb movement disorders after stroke in traditional Chinese medicine,systematically summarizes the clinical application and research progress of main treatment methods such as acupuncture,Chinese herbal medicine,and Tuina massage,analyzes the problems existing in current research,and looks forward to future development directions,aiming to provide references for clinical treatment.
文摘Objective To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as sia-lorrhea and hyperhidrosis. Methods A retrospective study of BTX-B injections in treatment of 58 patients with various neurological disorders was performed. The mean follow-up time was 0.9 ± 0.8 years. Results of the first and last treatment of patients with at least 3 injection sessions were compared. Results The response of 58 patients to a total of 157 BTX-B treatment sessions was analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in moderate or marked improvement while 17 sessions (10.8%) had no response. The clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41 patients with at least 3 injection ses-sions (mean 10 ± 8.6), most patients needed increased dosage upon the last session compared to the first session. Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with BTX-B treatment. Conclusions Though most patients require increased dosage to maintain effective response after repeated injections, BTX-B is an effective and safe treatment drug for a variety of movement disorders, as well as drooling and hyperhidrosis.
文摘Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and D2). Single photon emission computerized tomography (SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington’s disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette’s syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson’s disease (PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.
基金The study was reviewed and approved by the First Affiliated Hospital of Henan University of Science and Technology(Approval No.2022-03-B160).
文摘BACKGROUND The psychological state of patients with post stroke limb movement disorders undergoes a series of changes that affect rehabilitation training and recovery of limb motor function.AIM To determine the correlation between motor rehabilitation and the psychological state of patients with limb movement disorders after stroke.METHODS Eighty patients with upper and lower limb dysfunction post stroke were retrospectively enrolled in our study.Based on Hospital Anxiety and Depression Scale(HADS)scores measured before rehabilitation,patients with HADS scores≥8 were divided into the psychological group;otherwise,the patients were included in the normal group.Motor function and daily living abilities were compared between the normal and psychological groups.Correlations between the motor function and psychological status of patients,and between daily living ability and psychological status of patients were analyzed.RESULTS After 1,2,and 3 wk of rehabilitation,both the Fugl-Meyer assessment and Barthel index scores improved compared to their respective baseline scores(P<0.05).A greater degree of improvement was observed in the normal group compared to the psychological group(P<0.05).There was a negative correlation between negative emotions and limb rehabilitation(-0.592≤r≤-0.233,P<0.05),and between negative emotions and daily living ability(-0.395≤r≤-0.199,P<0.05).CONCLUSION There is a strong correlation between motor rehabilitation and the psychological state of patients with post stroke limb movement disorders.The higher the negative emotions,the worse the rehabilitation effect.
文摘Background Vocal cord movement disorder （VCMD） is a laryngeal disorder characterized by paradoxical adduction of the vocal cords during in inspiration, expiration or both. The nursing experience of patients with VCMD after aortic dissection surgery is limited. Methods We retrospectively analyzed the clinical data and nursing records of 269 patients after aortic dissection surgery in Guangdong General Hospital between May 2010 and May 2012. We observed the patients＇ pronunciation, and judged if there was dysphagia undergoing water drinking test two hours after extubation, to confirm whether patients had VCMD. Results Seventeen patients had VCMD after aortic dissection surgery, of whom 2 suffered hoarseness, 3 had dysphasia and 12 had both hoarseness and dysphasia. After timely treatment and carefully nursing, all the patients recovered well. Conclusions With the enhanced care of patients with aortic dissection, observing hoarseness appearance and drinking experiment immediately after extubation can detect VCMD as soon as possible. Further rehabilita- tion training and psychology care can prevent bucking and aspiration effectively, and promoting recovery and improving patient＇s life quality.
文摘BACKGROUND Spinal anesthesia is commonly used for various surgeries.While many complications occur after induction of spinal anesthesia,involuntary movement is an extremely rare complication.CASE SUMMARY Herein,we report the case of a 54-year-old healthy male patient who experienced involuntary movements after intrathecal injection of local anesthetics.This patient had undergone metal implant removal surgery in both the lower extremities;7 h after intrathecal hyperbaric bupivacaine administration,involuntary raising of the left leg began to occur every 2 min.When the movement disorder appeared,the patient was conscious and cooperative.No other specific symptoms were noted in the physical examination conducted immediately after the involuntary leg raising started;moreover,the patient's motor and sensory assessments were normal.The symptom gradually subsided.Twelve hours after the symptom first occurred,its frequency decreased to approximately once every three hours.Two days postoperatively,the symptoms had completely disappeared without intervention.CONCLUSION Anesthesiologists should be aware that movement disorders can occur after spinal anesthesia and be able to identify the cause,such as electrolyte imbalance or epilepsy,since immediate action may be required for treatment.Furthermore,it is crucial to know that involuntary movement that develop following spinal anesthesia is mostly self-limiting and may not require additional costly examinations.
基金Supported by The National Natural Science Foundation of China,Nos.81470456 and 81170160The priority Academic Program Development of Jiangsu Higher Education Institutions
文摘AIM:To investigate whether an association exists between sleep-associated movement disorders and cardiovascular disease(CVD).METHODS:Several studies have observed the relationship of sleep-associated movement disorders such as restless legs syndrome(RLS)and periodic limb movements during sleep with CVD,but the results were still contradictory.We performed an extensive literature search on Pub Med,Medline and Web of Science published from inception to December 2014.Additional studies were manually searched from bibliographies of retrieved studies.Meta-analyses were conducted with Stata version 12.0(Stata Corp,College Station,Texas).Pooled odds ratios(ORs)and 95%CIs were calculated to assess the strength of association using the random effects model.Sensitivity and subgroup analyses were performed to explore the underlying sources of heterogeneity.The publication bias was detected using Egger’s test and Begg’s test.RESULTS:A total of 781 unique citations were indentified from electronic databases and 13 articles in English were finally selected.Among these studies,nine are cohort studies;two are case-control studies;and two are cross-sectional studies.The results showed that the summary OR of CVD associated with sleepassociated movement was 1.51(95%CI:1.29-1.77)in a random-effects model.There was significant heterogeneity between individual studies(P for heterogeneity=0.005,I2=57.6%).Further analysis revealed that a large-scale cohort study may account for this heterogeneity.A significant association was also found between RLS and CVD(OR=1.54,95%CI:1.24-1.92).In a fixed-effects model,we determined a significant relationship between sleep-associatedmovement disorders and coronary artery disease(CAD)(OR=1.34,95%CI:1.16-1.54;P for heterogeneity=0.210;I2=30.0%).Our meta-analysis suggests that sleep-associated movement disorders are associated with prevalence of CVD and CAD.CONCLUSION:This finding indicates that sleep-associated movement disorders may prove to be predictive of underlying CVD.
文摘BACKGROUND Dystonic gait(DG) is one of clinical symptoms associated with functional dystonia in the functional movement disorders(FMDs). Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. There is no report for DG in FMDs caused by an abnormal pattern in the ankle muscle recruitment strategy during gait.CASE SUMMARY A 52-year-old male patient presented with persistent limping gait. When we requested him to do dorsiflexion and plantar flexion of his ankle in the standing and seating positions, we didn’t see any abnormality. However, we could see the DG during the gait. There were no evidences of common peroneal neuropathy and L5 radiculopathy in the electrodiagnostic study. Magnetic resonance imaging of the lumbar spine, lower leg, and brain had no definite finding. No specific finding was seen in the neurologic examination. For further evaluation, a wireless surface electromyography(EMG) was performed. During the gait, EMG amplitude of left medial and lateral gastrocnemius(GCM) muscles was larger than right medial and lateral GCM muscles. When we analyzed EMG signals for each muscle, there were EMG bursts of double-contraction in the left medial and lateral GCM muscles, while EMG analysis of right medial and lateral GCM muscles noted regular bursts of single contraction. We could find a cause of DG in FMDs.CONCLUSION We report an importance of a wireless surface EMG, in which other examination didn’t reveal the cause of DG in FMDs.
基金supported by Cincinnati Children’s Hospital Research Foundation。
文摘Background Sleep-related movement disorders(SRMDs),such as restless legs syndrome(RLS)and periodic limb movement disorder(PLMD),are common in pediatric sleep practice.There is increasing literature on RLS,PLMD,and a newly described sleep disorder called“restless sleep disorder(RSD)”.We aimed to review and provide recent updates on SRMDs.Data sources A comprehensive search for relevant English-language peer-reviewed publications focused on three common SRMDs,namely,RLS,PLMD and RSD,in a variety of indices in PubMed and SCOPUS.Both relevant databases and systematic reviews are included.Results SRMDs,especially RLS and PLMD,are common in children and adolescents.However,they are underrecognized.Genetics,abnormal dopaminergic functions,and iron deficiency are the main pathophysiologies of RLS and PLMD.RLS and RSD may share common pathophysiologic mechanisms,as evidenced by low iron stores in both conditions.The diagnoses of RLS,PLMD,and RSD require specific clinical criteria and polysomnographic features.Several comorbid conditions have been associated with RLS,PLMD,and RSD.Iron therapy has been shown to be effective for treating RLS,PLMD,and RSD.There is increasing evidence on the effectiveness of specific medications in children with RLS and PLMD,but the data are still limited.Conclusions This review summarizes the pathophysiology,clinical manifestations,diagnostic criteria,and management of RLS,PLMD,and RSD in children based on relevant and recent literature.It is important for pediatricians to recognize the clinical presentation of RLS,PLMD,and RSD to facilitate early diagnosis.Further studies are needed to examine the pathogenesis,long-term consequences,and pharmacologic therapy of RSD in children.
文摘Movement disorder management and therapy are rapidly evolving,owing to an ever-deeper understanding of disease biology and the discovery of new tools for diagnosis and treatment.With this narrative review,we aim to explore emerging therapeutic approaches for movement disorders,with a focus on Parkinson's disease(PD)and other movement-related pathological conditions,including Huntington's disease(HD),essential tremor(ET),and dystonia.This review encompasses preclinical research and human trials,providing a comprehensive overview of the current landscape.Several promising therapeutic strategies have emerged,particularly in the realm of precision medicine for PD associated with GBA and LRRK2 gene mutations.Additionally,innovative immunotherapies and drugs targeting misfoldedα-synuclein are under investigation.These approaches have the potential to influence disease progression and improve patient outcomes.The landscape of pharmacological treatments for movement disorders is both complex and diverse,with substantial progress made over the years.While current treatments effectively manage motor symptoms,they fall short of providing a definitive cure and are limited by nonmotor symptoms and potential side effects.Novel techniques,such as gene therapy,stem cell therapy,and infusion therapies,offer promising avenues for future research.
文摘Electrical stimulation has been used to influence the nervous system since ancient times,with early examples including the Egyptian use of electric fish for pain relief.The use of electrical stimulation to improve the understanding of brain regions and their functions advanced significantly in the 19th century,with experiments by Fritsch,Hitzig,and Bartholow,culminating in the development of techniques such as electrocorticography by Horsley.The field evolved with the development of stereotactic surgery in the 20th century,which allowed for the precise targeting of brain regions to treat movement disorders and chronic pain.Despite the advent of pharmacological treatments such as levodopa for Parkinson’s disease,surgical approaches such as thalamotomy and deep brain stimulation(DBS)remain crucial for patients who are unresponsive to medication.The refinement of DBS,particularly targeting the thalamus and subthalamic nucleus,has revolutionized the treatment of movement disorders and resulted in the widespread adoption of this technique.In contrast,early psychiatric treatments were typically rudimentary and driven by the dire conditions of mental asylums rather than scientific understanding.DBS has also been extended to the treatment of psychiatric disorders.Early studies conducted in the late 1990s and the early 2000s showed promising results for conditions such as obsessive-compulsive disorder.However,evidence of its efficacy in psychiatric conditions remains mixed,and ongoing research is required to establish its role.Ethical considerations are of paramount importance in this field,particularly concerning the safety,informed consent,and long-term effects of DBS.In contrast to movement disorders,psychiatric conditions experience challenges such as unclear biomarkers,subjective diagnoses,and unpredictable treatment responses,rendering DBS development in this area more complicated.
基金supported by National Natural Science Foundation of China(82071686)Clinical Research Fund of West China Second University Hospital,Sichuan University(KL115,KL072).
文摘Genetic developmental and epileptic encephalopathies(DEE)are often associated with movement disorders.Accurate identification and classification of movement disorders are essential for management of these diseases.In this review,we describe the characteristics of various movement disorders associated with DEE and summarize the distribution of common DEE-related gene mutations reported in previous studies,aiming to provide references for the diagnosis and treatment of these disorders.
文摘Background:Parkinson’s Disease(PD)is characterized by motor and non‐motor symptoms that can overlap with other movement disorders,complicating accurate diagnosis and monitoring.Wearable technologies,such as smartwatches,offer continuous and objective assessment of motor function,but their clinical utility in multiclass classification and symptom prediction remains underexplored.This study aimed to determine whether smartwatch‐derived motor features can distinguish idiopathic PD from other movement disorders and whether motor variability is associated with non‐motor symptom burden in PD.Methods:We analyzed data from the Parkinson’s Disease Smartwatch(PADS)dataset(N=469),which includes accelerometer and gyroscope signals recorded during 20 standardized motor tasks.For each participant,mean and standard deviation values for each axis were averaged across tasks.Diagnostic group classification was assessed using multinomial logistic regression.Among individuals with idiopathic PD(n=276),linear regression evaluated associations between motor variability and total non‐motor symptom scores from a 30‐item questionnaire.Results:Motor variability features,particularly accelerometer Y‐axis and gyroscope X‐axis standard deviations,significantly differentiated diagnostic groups(pseudo R2=0.068).Age,sex,and handedness also contributed.In the PD subgroup,higher accelerometer X and gyroscope X variability were associated with greater non‐motor symptom burden,while greater stability in the mediolateral(Y)axis was linked to fewer symptoms(adjusted R2=0.0081,p<0.001).Conclusion:Smartwatch‐derived motor variability features can modestly differentiate movement disorder diagnoses and are associated with non‐motor symptom severity in PD.Our findings support the complementary use of wearable sensors in clinical assessment and remote monitoring.Our findings also lay the foundation for future integration of wearable‐derived data into telemedicine workflows.
基金the National Natural Science Foundation of China(No.81730050).
文摘Background:Reports evaluating the efficacy of transcranial sonography(TCS)for the differential diagnosis of Parkinson disease(PD)and other movement disorders in China are scarce.Therefore,this study aimed to assess the application of TCS for the differential diagnosis of PD,multiple system atrophy(MSA),progressive supranuclear palsy(PSP),and essential tremor(ET)in Chinese individuals.Methods:From 2017 to 2019,500 inpatients treated at the Department of Dyskinesia,Beijing Tiantan Hospital,Capital Medical University underwent routine transcranial ultrasound examination.The cross-sections at the midbrain and thalamus levels were scanned,and the incidence rates of substantia nigra(SN)positivity and the incidence rates of lenticular hyperechoic area were recorded.The echo of the SN was manually measured.Results:Of the 500 patients,125 were excluded due to poor signal in temporal window sound transmission.Among the 375 individuals with good temporal window sound transmission,200 were diagnosed with PD,90 with ET,50 with MSA,and 35 with PSP.The incidence rates of SN positivity differed significantly among the four patient groups(χ^(2)=121.061,P<0.001).Between-group comparisons were performed,and the PD group showed a higher SN positivity rate than the ET(χ^(2)=94.898,P<0.017),MSA(χ^(2)=57.619,P<0.017),and PSP(χ^(2)=37.687,P<0.017)groups.SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases,collectively or individually.The incidences of lenticular hyperechoic area significantly differed among the four patient groups(χ^(2)=38.904,P<0.001).Next,between-group comparisons were performed.The lenticular hyperechoic area was higher in the PD group than in the ET(χ^(2)=6.714,P<0.017)and MSA(χ^(2)=18.680,P<0.017)groups but lower than that in the PSP group(χ^(2)=0.679,P>0.017).Conclusion:SN positivity could effectively differentiate PD from ET,PSP,and MSA in a Chinese population.
基金supported by Key Research Project of the Ministry of Science and Technology of China(Grant Nos.2016YFC0904400 and 2016YFC0904401).
文摘Background:RHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64),which is characterized by epilepsy,developmental delay,microcephaly,unspecific facial dysmorphism,and paroxysmal movement disorders.Most previous studies showed that the phenotypes of RHOBTB2 gene include developmental and epileptic encephalopathy(DEE)and DEE with paroxysmal movement disorders.Only one study showed that patient with RHOBTB2 variant had paroxysmal movement disorders with no epilepsy.Case presentations:Two cases with RHOBTB2 variants are presented here:Case one was diagnosed as DEE,he had recurrent afebrile focal status epilepticus and paroxysmal extrapyramidal symptoms in infancy.Interictal electroencephalogram(EEG)showed focal discharges.Brain magnetic resonance imaging(MRI)showed cortical dysplasia.Epilepsy of case one was refractory.Nevertheless,case two only showed paroxysmal movement disorders alone in adolescence.Video EEG showed focal discharges during an interictal dystonic episode and he brain MRI was normal.Conclusion:The phenotypes of RHOBTB2 gene include DEE,paroxysmal movement disorders,and DEE with paroxysmal movement disorders.RHOBTB2 can be one of the pathogenic genes of paroxysmal movement disorders.
文摘Previous reports on the pathogenesis of age-related movement disorders,such as Parkinson’s disease(PD)and essential tremor(ET),have demonstrated the potential implications of LINGO1(leucine-rich repeat and immunoglobulin domain-containing protein)gene.Although LINGO2 has a high degree of homology with LINGO1,but it is less characterized and the role of LINGO2 in the development of PD/ET remains unreported.Hence,this metaanalysis was conducted to evaluate the role of LINGO2 in PD/ET pathogenesis.A total of 4 studies,which complied with the Hardy-Weinberg equilibrium,were included in the meta-analysis.Analysis of the pooled odds ratio and confidence interval of the studies were performed for five genetic models,namely:allelic,dominant,recessive,homozygous,and heterozygous.No significant association was observed between the LINGO2 polymorphism and PD/ET,although subgroup analysis through conventional metaanalysis indicated that the recessive models of rs7033345 and rs10812774 are significantly associated with predisposition to ET in the Asian population.However,trial sequential analyses for both polymorphisms were unlikely to reveal any robust effect.Hence,studies with larger samples on this association are needed in the future to corroborate our results.
基金supported by STI 2030-Major Projects,No.2021ZD0201603(to JL)the Joint Foundation Program of the Chinese Academy of Sciences,No.8091A170201(to JL)+1 种基金the National Natural Science Foundation of China,Nos.T2293730(to XC),T2293731(to XC),T2293734(to XC),62471291(to YW),62121003(to XC),61960206012(to XC),62333020(to XC),and 62171434(to XC)the National Key Research and Development Program of China,Nos.2022YFC2402501(to XC),2022YFB3205602(to XC).
文摘Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
文摘α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
