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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan department of neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key Laboratory for neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

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Neural Regeneration Research 2025年第1期20卷 82-92页

作者： Stiven Roytman Rebecca Paalanen Giulia Carli Uros Marusic Prabesh Kanel Teus van Laar Nico I.Bohnen department of Radiology University of MichiganAnn ArborMIUSA department of neurology University of MichiganAnn ArborMIUSA Morris K.Udall Center of Excellence for Parkinson’s Disease Research University of MichiganAnn ArborMIUSA Institute for Kinesiology Research Science and Research Centre KoperKoperSlovenia department of Health Sciences Alma Mater Europaea–ECMMariborSlovenia Parkinson’s Foundation Research Center of Excellence University of MichiganAnn ArborMIUSA department of neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands neurology Service and GRECC VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

关键词： aging balance encephalography functional magnetic resonance imaging gait multisensory integration Parkinson’s disease positron emission tomography somatosensory vestibular visual

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

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Stroke & Vascular neurology 2024年第1期9卷 75-81,I0047-I0052页

作者： Xiaoling Liao Shuo Feng Yicong Wang Yuesong Pan Weiqi Chen Hui Qu Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang department of neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical Research Center for Neurological Diseases Beijing TiantanHospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina National Center for Neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen.Tirofiban,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic stroke.However,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear.Aim To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination.Methods Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in China.Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90.The primary endpoint is a new stroke or END within 90 days.The primary safety endpoint is severe or moderate bleeding within 90 days.Discussion The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.Trial registration number NCT05310968.

关键词： Aspirin regimen centre

Serotonin syndrome controversies:A need for consensus

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World Journal of Critical Care Medicine 2024年第2期13卷 150-158页

作者： Sanjay Prakash Chetsi S Shah Anurag Prakash department of neurology Smt.B.K.Shah Medical Institute and Research CentreSumandeep VidyapeethVadodara 391760GujarātIndia Medicine Parul Institute of Medical Sciences and Research CentreParul University WaghodiaVadodara 391760India

Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.

关键词： Serotonin Serotonin syndrome Serotonin toxicity Selective serotonin reuptake inhibitors Antidepressants Cyproheptadine

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan clinical Medical School Beijing Huilongguan HospitalBeijing 100096China department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA department of Medicine Harvard Medical SchoolBostonMA 02115USA department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China department of neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong department of neurology of the Second Afliated Hospital and department of Human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China department of Physiology and department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of Human Reproduction and Developmental Genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

Early identification of stroke through deep learning with multi-modal human speech and movement data

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Neural Regeneration Research 2025年第1期20卷 234-241页

作者： Zijun Ou Haitao Wang Bin Zhang Haobang Liang Bei Hu Longlong Ren Yanjuan Liu Yuhu Zhang Chengbo Dai Hejun Wu Weifeng Li Xin Li School of Computer Science and Engineering Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina department of Emergency Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina

Early identification and treatment of stroke can greatly improve patient outcomes and quality of life.Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized training.In this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute settings.We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the FAST.We compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and MViT.We found that the findings of our deep learning model had a higher clinical value compared with the other approaches.Moreover,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech audio.These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

关键词： artificial intelligence deep learning diagnosis early detection FAST screening stroke

Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi department of Veterinary Sciences University of TurinGrugliascoTOItaly department of Psychiatry and neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical cord.MSCs have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue repair.MSCs enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC secretome.An increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

Biofluid Biomarkers of Alzheimer's Disease:Progress,Problems,and Perspectives

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neuroscience Bulletin 2022年第6期38卷 677-691页

作者： Shan Huang Yan-Jiang Wang Junhong Guo department of neurology First HospitalShanxi Medical UniversityTaiyuan 030000China department of neurology and centre for clinical neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China

Since the establishment of the biomarker-based A-T-N(Amyloid/Tau/Neurodegeneration)framework in Alzheimer's disease(AD),the diagnosis of AD has become more precise,and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted.However,the A-T-N framework does not encompass the whole spectrum of AD pathologies,and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system.Therefore,we suggest the addition of an“X”to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD.In this review,we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework,analyze the problems,and present our perspectives on the diagnosis of AD.

关键词： Alzheimer's disease Biomarker Amyloidbeta Tau Diagnosis