Objective Linguistic problem is common in Huntington’s disease(HD)patients.It has been studied before in native speakers of alphabetic languages,such as English.As a hieroglyphic language,Chinese differs from alphabe...Objective Linguistic problem is common in Huntington’s disease(HD)patients.It has been studied before in native speakers of alphabetic languages,such as English.As a hieroglyphic language,Chinese differs from alphabetic languages in terms of phonology,morphology,semantics and syntax.We aimed to investigate the linguistic characteristics of manifest HD in native speakers of Mandarin.Meanwhile,we expected to explore the linguistic differences associated with cortical or subcortical pathology.Methods Five HD patients and five Alzheimer’s disease(AD)patients matched in age,gender,disease course and educational level were enrolled.All the participants were Mandarin native speakers.All finished history inquiry,physical examination,basic test,genetic test and neuropsychological assessment.Language evaluation was performed by Aphasia Battery of Chinese.Results HD patients had a mean disease course of 5.4±2.97(range,2-10)years.They showed a linguistic disorder close to transcortical motor aphasia.They exhibited prominent phonological impairment,as well as slight semantic and syntactic abnormality.Tonic errors were found in speech.Character structural errors and substitutions were detected in writing.In comparison,AD patients showed a more severe linguistic impairment,characterized by global aphasia with more semantic errors.Conclusion Mandarin-speaking HD patients have a transcortical motor aphasia-like disturbance with prominent phonological impairment,whereas AD patients have a more severe global aphasia with salient semantic impairment.展开更多
Facial synkinesis is one of the most severe sequelae of facial nerve paralysis,and it can result in facial movement disorders,abnormal facial expressions,and even problems of social communication.The underlying mechan...Facial synkinesis is one of the most severe sequelae of facial nerve paralysis,and it can result in facial movement disorders,abnormal facial expressions,and even problems of social communication.The underlying mechanism of postparalysis facial synkinesis remains unclear.In recent years,researchers have demonstrated several possible mechanisms of facial synkinesis,including aberrant regeneration,ephaptic transmission,overacting of the facial nucleus in the pons,and changes in the cerebral cortex.Management includes botulinum toxin type A(BTX-A)injection,surgery,and neuromuscular reeducation.展开更多
Background:In the clinic,practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging(MRI)signal in the basal ganglia,a phenomenon known as"cheese sign".This si...Background:In the clinic,practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging(MRI)signal in the basal ganglia,a phenomenon known as"cheese sign".This sign is reported as common in cerebrovascular diseases,dementia,and old age.Recently,cheese sign has been speculated to consist of dense perivascular space(PVS).This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods:A total of 812 patients from Peking Union Medical College Hospital(PUMCH)dementia cohort were enrolled.We analyzed the relationship between cheese sign and vascular risk.For assessing cheese sign and defining its degree,the abnormal punctate signals were classified into basal ganglia hyperintensity(BGH),PVS,lacunae/infarctions and microbleeds,and counted separately.Each type of lesion was rated on a four-level scale,and then the sum was calculated;this total was defined as the cheese sign score.Fazekas and Age-Related White Matter Changes(ARWMC)scores were used to evaluate the paraventricular,deep,and subcortical gray/white matter hyperintensities.Results:A total of 118 patients(14.5%)in this dementia cohort were found to have cheese sign.Age(odds ratio[OR]:1.090,95%confidence interval[CI]:1.064-1.120,P<0.001),hypertension(OR:1.828,95%CI:1.123-2.983,P=0.014),and stroke(OR:1.901,95%CI:1.092-3.259,P=0.025)were risk factors for cheese sign.There was no significant relationship between diabetes,hyperlipidemia,and cheese sign.The main components of cheese sign were BGH,PVS,and lacunae/infarction.The proportion of PVS increased with cheese sign severity.Conclusions:The risk factors for cheese sign were hypertension,age,and stroke.Cheese sign consists of BGH,PVS,and lacunae/infarction.展开更多
To the Editor:Idiopathic normal pressure hydrocephalus(iNPH)patients present disturbances in gait,cognition,and/or control of urination with neuroimaging characterized by enlargement of the cerebral ventricles.Typical...To the Editor:Idiopathic normal pressure hydrocephalus(iNPH)patients present disturbances in gait,cognition,and/or control of urination with neuroimaging characterized by enlargement of the cerebral ventricles.Typically,gait disturbance in iNPH patients is the initial and most prominent symptom,but motor impairments can also extend to upper extremity.The cerebrospinaluid(CSF)tap test(TT),in which the symptoms of iNPH patients are assessed before and after drainage of 30-50mL CSF by lumbar puncture,is a commonly used auxiliary test for predicting shunt responsiveness.Standard methods for determining the CSF TT response are based on the clinical impression of changes in gait after lumber puncture.iNPH patients who are unable to ambulate(e.g.,the patient is wheelchair bound)may not be able to comply with the gait evaluation but still benet from shunt placement.The grooved pegboard test(GPT)and symbol-digit modalities test(SDMT)are psychometric measures of upper extremity motor and psychomotor speed.Herein,we sought to identify whether these tests could be used to objectively assess responsiveness to the CSF TT.展开更多
Background and purpose Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China,but its underlying risk genes and pathways are far from being comprehen...Background and purpose Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China,but its underlying risk genes and pathways are far from being comprehensively understood.We here describe the design and methods of whole genome sequencing(WGS)for 10914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry(CNSR-III).Methods Baseline clinical characteristics of the included patients in this study were reported.DNA was extracted from white blood cells of participants.Libraries are constructed using qualified DNA,and WGS is conducted on BGISEQ-500 platform.The average depth is intended to be greater than 30×for each subject.Afterwards,Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants(SNVs)and insertion-deletions.For each included subject,21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual.The copy number variations and structural variations are also called for each patient.All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases.Results The average age of the included 10914 patients was 62.2±11.3 years,and 31.4%patients were women.Most of the baseline clinical characteristics of the 10914 and the excluded patients were balanced.Conclusions The WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke.展开更多
Background Somatic mutation contributes to clonal haematopoiesis of indeterminate potential(CHIP)is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease.Here,we investi...Background Somatic mutation contributes to clonal haematopoiesis of indeterminate potential(CHIP)is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease.Here,we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke(AIS)cohort and explored the underlying mechanisms.Methods We studied a prospective cohort of 6016 patients who had a first-ever AIS in China.Whole-genome sequencing was performed to identify CHIP.High-sensitivity C reactive protein(hs-CRP)levels above 3 mg/L at baseline were defined as hyperinflammation.Recurrent stroke during the 3-month follow-up was the primary outcome.Results Among the 6016 patients who had a first-ever AIS,with a median age was 62 years(IQR,54.0‒70.0),3.70%were identified as CHIP carriers.The most common mutations occurred in the DNMT3A(30.0%)and TET2(11.4%)genes.During a follow-up of 3 months,the presence of CHIP was associated with recurrent stroke(HR 1.62,95%CI 1.04 to 2.51,p=0.03),recurrent ischaemic stroke(HR 1.64,95%CI 1.04 to 2.58,p=0.03)and combined vascular events(HR 1.58,95%CI 1.02 to 2.44,p=0.04)after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS.Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation(OR 3.10,95%CI 1.92 to 5.00,p<0.001)but not in those without hyperinflammation(OR 0.18,95%CI 0.03 to 1.04,p=0.06,Pinteraction=0.002).Conclusion Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS.Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.展开更多
基金supported by grants from CAMS Innovation Fund for Medical Sciences(No.2016-I2M-1-004)National Natural Science Foundation of China(No.81550021)+1 种基金13th Five-year National Key Research and Development Program of China(No.2016YFC1306300)the strategic priority research program(pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(XDPB10)。
文摘Objective Linguistic problem is common in Huntington’s disease(HD)patients.It has been studied before in native speakers of alphabetic languages,such as English.As a hieroglyphic language,Chinese differs from alphabetic languages in terms of phonology,morphology,semantics and syntax.We aimed to investigate the linguistic characteristics of manifest HD in native speakers of Mandarin.Meanwhile,we expected to explore the linguistic differences associated with cortical or subcortical pathology.Methods Five HD patients and five Alzheimer’s disease(AD)patients matched in age,gender,disease course and educational level were enrolled.All the participants were Mandarin native speakers.All finished history inquiry,physical examination,basic test,genetic test and neuropsychological assessment.Language evaluation was performed by Aphasia Battery of Chinese.Results HD patients had a mean disease course of 5.4±2.97(range,2-10)years.They showed a linguistic disorder close to transcortical motor aphasia.They exhibited prominent phonological impairment,as well as slight semantic and syntactic abnormality.Tonic errors were found in speech.Character structural errors and substitutions were detected in writing.In comparison,AD patients showed a more severe linguistic impairment,characterized by global aphasia with more semantic errors.Conclusion Mandarin-speaking HD patients have a transcortical motor aphasia-like disturbance with prominent phonological impairment,whereas AD patients have a more severe global aphasia with salient semantic impairment.
文摘Facial synkinesis is one of the most severe sequelae of facial nerve paralysis,and it can result in facial movement disorders,abnormal facial expressions,and even problems of social communication.The underlying mechanism of postparalysis facial synkinesis remains unclear.In recent years,researchers have demonstrated several possible mechanisms of facial synkinesis,including aberrant regeneration,ephaptic transmission,overacting of the facial nucleus in the pons,and changes in the cerebral cortex.Management includes botulinum toxin type A(BTX-A)injection,surgery,and neuromuscular reeducation.
基金National Key Research and Development Program of China(Nos.2020YFA0804500 and 2020YFA0804501)CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-I2M-1-020 and 2020-I2M-C&T-B-010)+1 种基金National Natural Science Foundation of China(Nos.81550021 and 30470618)Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Project(No.2021ZD0201106)
文摘Background:In the clinic,practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging(MRI)signal in the basal ganglia,a phenomenon known as"cheese sign".This sign is reported as common in cerebrovascular diseases,dementia,and old age.Recently,cheese sign has been speculated to consist of dense perivascular space(PVS).This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods:A total of 812 patients from Peking Union Medical College Hospital(PUMCH)dementia cohort were enrolled.We analyzed the relationship between cheese sign and vascular risk.For assessing cheese sign and defining its degree,the abnormal punctate signals were classified into basal ganglia hyperintensity(BGH),PVS,lacunae/infarctions and microbleeds,and counted separately.Each type of lesion was rated on a four-level scale,and then the sum was calculated;this total was defined as the cheese sign score.Fazekas and Age-Related White Matter Changes(ARWMC)scores were used to evaluate the paraventricular,deep,and subcortical gray/white matter hyperintensities.Results:A total of 118 patients(14.5%)in this dementia cohort were found to have cheese sign.Age(odds ratio[OR]:1.090,95%confidence interval[CI]:1.064-1.120,P<0.001),hypertension(OR:1.828,95%CI:1.123-2.983,P=0.014),and stroke(OR:1.901,95%CI:1.092-3.259,P=0.025)were risk factors for cheese sign.There was no significant relationship between diabetes,hyperlipidemia,and cheese sign.The main components of cheese sign were BGH,PVS,and lacunae/infarction.The proportion of PVS increased with cheese sign severity.Conclusions:The risk factors for cheese sign were hypertension,age,and stroke.Cheese sign consists of BGH,PVS,and lacunae/infarction.
基金National Key Research and Development Program of China(No.2020YFA0804500)CAMS Innovation fund for Medical Sciences(No.2016-12 M-1-004)National Natural Science Foundation of China(No.81550021)
文摘To the Editor:Idiopathic normal pressure hydrocephalus(iNPH)patients present disturbances in gait,cognition,and/or control of urination with neuroimaging characterized by enlargement of the cerebral ventricles.Typically,gait disturbance in iNPH patients is the initial and most prominent symptom,but motor impairments can also extend to upper extremity.The cerebrospinaluid(CSF)tap test(TT),in which the symptoms of iNPH patients are assessed before and after drainage of 30-50mL CSF by lumbar puncture,is a commonly used auxiliary test for predicting shunt responsiveness.Standard methods for determining the CSF TT response are based on the clinical impression of changes in gait after lumber puncture.iNPH patients who are unable to ambulate(e.g.,the patient is wheelchair bound)may not be able to comply with the gait evaluation but still benet from shunt placement.The grooved pegboard test(GPT)and symbol-digit modalities test(SDMT)are psychometric measures of upper extremity motor and psychomotor speed.Herein,we sought to identify whether these tests could be used to objectively assess responsiveness to the CSF TT.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China(2016YFC0901002,2016YFC0901001)Beijing Municipal Science&Technology Commission(D171100003017002)+1 种基金Beijing Municipal Administration of Hospitals’Mission Plan(SML20150502)National Science and Technology Major Project(2017ZX09304018)。
文摘Background and purpose Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China,but its underlying risk genes and pathways are far from being comprehensively understood.We here describe the design and methods of whole genome sequencing(WGS)for 10914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry(CNSR-III).Methods Baseline clinical characteristics of the included patients in this study were reported.DNA was extracted from white blood cells of participants.Libraries are constructed using qualified DNA,and WGS is conducted on BGISEQ-500 platform.The average depth is intended to be greater than 30×for each subject.Afterwards,Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants(SNVs)and insertion-deletions.For each included subject,21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual.The copy number variations and structural variations are also called for each patient.All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases.Results The average age of the included 10914 patients was 62.2±11.3 years,and 31.4%patients were women.Most of the baseline clinical characteristics of the 10914 and the excluded patients were balanced.Conclusions The WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke.
基金supported by grants from National Natural Science Foundation of China(grant number 82171270,81870905,U20A20358)Natural Science Foundation of Beijing(Z200016)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029).
文摘Background Somatic mutation contributes to clonal haematopoiesis of indeterminate potential(CHIP)is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease.Here,we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke(AIS)cohort and explored the underlying mechanisms.Methods We studied a prospective cohort of 6016 patients who had a first-ever AIS in China.Whole-genome sequencing was performed to identify CHIP.High-sensitivity C reactive protein(hs-CRP)levels above 3 mg/L at baseline were defined as hyperinflammation.Recurrent stroke during the 3-month follow-up was the primary outcome.Results Among the 6016 patients who had a first-ever AIS,with a median age was 62 years(IQR,54.0‒70.0),3.70%were identified as CHIP carriers.The most common mutations occurred in the DNMT3A(30.0%)and TET2(11.4%)genes.During a follow-up of 3 months,the presence of CHIP was associated with recurrent stroke(HR 1.62,95%CI 1.04 to 2.51,p=0.03),recurrent ischaemic stroke(HR 1.64,95%CI 1.04 to 2.58,p=0.03)and combined vascular events(HR 1.58,95%CI 1.02 to 2.44,p=0.04)after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS.Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation(OR 3.10,95%CI 1.92 to 5.00,p<0.001)but not in those without hyperinflammation(OR 0.18,95%CI 0.03 to 1.04,p=0.06,Pinteraction=0.002).Conclusion Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS.Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.