Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs ma...Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.展开更多
Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory.Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide(H2S) and ca...Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory.Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide(H2S) and calcium ion overload.Aminooxyacetic acid is a cystathionine-β-synthase activity inhibitor that can reduce H2S formation in the brain.This study sought to observe the effect of aminooxyacetic acid on learning and memory in a chronic alcoholism rat model.Rats were randomly divided into three groups.Rats in the control group were given pure water for 28 days.Rats in the model group were given 6% alcohol for 28 days to establish an alcoholism rat model.Rats in the aminooxyacetic acid remedy group were also given 6% alcohol for 28 days and were also intraperitoneally injected daily with aminooxyacetic acid(5 mg/kg) from day 15 to day 28.Learning and memory was tested using the Morris water maze test.The ultrastructure of mitochondria in the hippocampus was observed by electron microscopy.H2S levels in the hippocampus were measured indirectly by spectrophotometry,and ATPase activity was measured using a commercial kit.The expression of myelin basic protein was determined by immunohistochemistry and western blotting.Compared with the control group,latency and swimming distance were prolonged in the navigation test on days 2,3,and 4 in the model group.In the spatial probe test on day 5,the number of platform crosses was reduced in the model group.Cristae cracks,swelling or deformation of mitochondria appeared in the hippocampus,the hippocampal H2S level was increased,the mitochondrial ATPase activity was decreased,and the expression of myelin basic protein in the hippocampus was down-regulated in the model group compared with the control group.All the above indexes were ameliorated in the aminooxyacetic acid remedy group compared with the model group.These findings indicate that aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model,which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity,and up-regulation of myelin basic protein levels in the hippocampus.展开更多
Objective GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease(NIID).Given the clinical overlap of cognitive impairment in NIID and cere...Objective GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease(NIID).Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease(CSVD),both diseases have white matter hyperintensity on T2-fluid attenuated inversion recovery sequences of brain MRI,and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI.Therefore,we hypothesised that the GGC repeat expansions might also contribute to CSVD.To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD,we performed a genetic analysis of 814 patients with the disease.Methods We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD.Their Fazekas score was greater than or equal to 3 points.Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions,and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD.Results We identified nine(1.11%)patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats.The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%.Conclusion Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD.This provides new thinking for studying the pathogenesis of CSVD.展开更多
Background Stroke is the leading cause of mortality in China,with limited evidence of in-hospital burden obtained from nationwide surveys.We aimed to monitor and track the temporal trends and rural-urban disparities i...Background Stroke is the leading cause of mortality in China,with limited evidence of in-hospital burden obtained from nationwide surveys.We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors,management and outcomes from 2005 to 2015.Methods We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005,2010 and 2015.We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach.We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.Results We analysed 28277 ischaemic stroke admissions from 189 participating hospitals.From 2005 to 2015,the estimated national hospital admission rate for ischaemic stroke per 100000 people increased(from 75.9 to 402.7,Ptrend<0.001),and the prevalence of risk factors,including hypertension,diabetes,dyslipidaemia and current smoking,increased.The composite score of diagnostic tests for stroke aetiology assessment(from 0.22 to 0.36,Ptrend<0.001)and secondary prevention treatments(from 0.46 to 0.70,Ptrend<0.001)were improved.A temporal decrease was found in discharge against medical advice(DAMA)(from 15.2%(95%CI 13.7%to 16.7%)to 8.6%(8.1%to 9.0%);adjusted Ptrend=0.046),and decreases in in-hospital mortality(0.7%in 2015 vs 1.8%in 2005;adjusted OR(aOR)0.52;95%CI 0.32 to 0.85)and the composite outcome of in-hospital mortality or DAMA(8.4%in 2015 vs 13.9%in 2005;aOR 0.65;95%CI 0.47 to 0.89)were observed.Disparities between rural and urban hospitals narrowed;however,disparities persisted in in-hospital management(brain MRI:rural-urban difference from−14.4%to−11.2%;cerebrovascular assessment:from−20.3%to−16.7%;clopidogrel:from−2.1%to−10.3%;anticoagulant for atrial fibrillation:from−10.9%to−8.2%)and in-hospital outcomes(DAMA:from 2.7%to 5.0%;composite outcome of in-hospital mortality or DAMA:from 2.4%to 4.6%).Conclusions From 2005 to 2015,improvements in hospital admission and in-hospital management for ischaemic stroke in China were found.A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed.Disparities between rural and urban hospitals generally narrowed but persisted.展开更多
Background: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing...Background: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients. Methods: We performed an open-label prospective study in genetically confirmed adult (〉18 years old) SCA3 patients. NGF was administered by intramuscular injection (18 μg once daily) fbr 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA). Results: Twenty-one SCA3 patients ( 10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77,57 ± 2.27) were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48± 2.40 to 6.30 ± 1.87 (P 〈 0.001 ). Subsections SARA scores also showed significant improvements in stance (P = 0.003), speech (P = 0.023), finger chase (P = 0.015), fast alternating hand movements (P = 0.009), and heel-shin slide (P = 0.001). Conclusions: Our preliminary data suggest that NGF may be effective in treating patients with SCA3.展开更多
Background:The 9-hole peg test (9-HPT) and 10-meter walk test (10-MWT) are commonly used to test finger motor function and walking ability.The aim of this present study was to investigate the efficacy of these te...Background:The 9-hole peg test (9-HPT) and 10-meter walk test (10-MWT) are commonly used to test finger motor function and walking ability.The aim of this present study was to investigate the efficacy of these tests for evaluating functional loss in Chinese Charcot-Marie-Tooth (CMT) disease.Methods:Thirty-four Chinese CMT patients (CMT group) from August 2015 to December 2016 were evaluated with 9-HPT,10-MWT,CMT disease examination score,overall neuropathy limitation scale (ONLS),functional disability score,and Berg Balance Scale (BBS).Thirty-five age-and gender-matched healthy controls (control group) were also included in the study.Student's nonpaired or paired t-test were performed to compare data between two independent or related groups,respectively.The Pearson test was used to examine the correlations between recorded parameters.Results:The mean 9-HPT completion time in the dominant hand of CMT patients was significantly slower than that in the healthy controls (29.60 ± 11.89 s vs.19.58 ± 3.45 s;t =-4.728,P 〈 0.001).Women with CMT completed the 9-HPT significantly faster than men with CMT (dominant hand:24.74 ± 7.93 s vs.33.01 ± 13.14 s,t =2.097,P =0.044).The gait speed of the average self-selected velocity and the average fast-velocity assessed using 10-MWT for CMT patients were significantly slower than those in the control group (1.03 ± 0.18 m/s vs.1.44 ± 0.17 m/s,t =9.333,P 〈 0.001;1.31 ± 0.30 m/s vs.1.91 ± 0.25 m/s,t =8.853,P 〈 0.00 1,respectively).There was no difference in gait speed between men and women.Both 9-HPT and 10-MWT were significantly correlated with the ONLS,functional disability score,and BBS (P 〈 0.05 for all).Conclusion:The 9-HPT and 10-MWT might be useful for functional assessment in Chinese patients with CMT.展开更多
Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the presen...Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.Additionally,white matter progression is an independent risk factor,which may be a potential therapeutic target.展开更多
基金supported by grants from the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2019ZX09301159)the“Thousand Talent Program”for Science and Technology Innovation Leader in Henan(No.194200510002)+1 种基金the Bingtuan Science and Technology Project(No.2019AB034)the Natural Science Foundation of Henan Province of China(No.202300410381).
文摘Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.
基金supported by the National Natural Science Foundation of China(to YMX),No.81530037,81471158a grant from the Department of Education of Henan Province of China(to ALD),No.15A310006
文摘Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory.Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide(H2S) and calcium ion overload.Aminooxyacetic acid is a cystathionine-β-synthase activity inhibitor that can reduce H2S formation in the brain.This study sought to observe the effect of aminooxyacetic acid on learning and memory in a chronic alcoholism rat model.Rats were randomly divided into three groups.Rats in the control group were given pure water for 28 days.Rats in the model group were given 6% alcohol for 28 days to establish an alcoholism rat model.Rats in the aminooxyacetic acid remedy group were also given 6% alcohol for 28 days and were also intraperitoneally injected daily with aminooxyacetic acid(5 mg/kg) from day 15 to day 28.Learning and memory was tested using the Morris water maze test.The ultrastructure of mitochondria in the hippocampus was observed by electron microscopy.H2S levels in the hippocampus were measured indirectly by spectrophotometry,and ATPase activity was measured using a commercial kit.The expression of myelin basic protein was determined by immunohistochemistry and western blotting.Compared with the control group,latency and swimming distance were prolonged in the navigation test on days 2,3,and 4 in the model group.In the spatial probe test on day 5,the number of platform crosses was reduced in the model group.Cristae cracks,swelling or deformation of mitochondria appeared in the hippocampus,the hippocampal H2S level was increased,the mitochondrial ATPase activity was decreased,and the expression of myelin basic protein in the hippocampus was down-regulated in the model group compared with the control group.All the above indexes were ameliorated in the aminooxyacetic acid remedy group compared with the model group.These findings indicate that aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model,which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity,and up-regulation of myelin basic protein levels in the hippocampus.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences[grant number 2020-PT310-01]the National Natural Science Foundation of China to Dr.Chang-he Shi[grant number 82171247,81974211]the National Natural Science Foundation of China to Dr.Yu-ming Xu[grant numbers U1904207].
文摘Objective GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease(NIID).Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease(CSVD),both diseases have white matter hyperintensity on T2-fluid attenuated inversion recovery sequences of brain MRI,and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI.Therefore,we hypothesised that the GGC repeat expansions might also contribute to CSVD.To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD,we performed a genetic analysis of 814 patients with the disease.Methods We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD.Their Fazekas score was greater than or equal to 3 points.Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions,and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD.Results We identified nine(1.11%)patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats.The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%.Conclusion Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD.This provides new thinking for studying the pathogenesis of CSVD.
基金Ministry of Science and Technology of the People’s Republic of China(National Key R&D Programme of China,2017YFC1310901,2016YFC0901002,2017YFC1307905,2015BAI12B00)National Natural Science Foundation of China(No.81801152,92046016)+1 种基金Beijing Natural Science Foundation(Z200016),Beijing Talents Project(2018000021223ZK03)Youth Programme(QML20180501)and Sanofi funding.
文摘Background Stroke is the leading cause of mortality in China,with limited evidence of in-hospital burden obtained from nationwide surveys.We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors,management and outcomes from 2005 to 2015.Methods We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005,2010 and 2015.We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach.We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.Results We analysed 28277 ischaemic stroke admissions from 189 participating hospitals.From 2005 to 2015,the estimated national hospital admission rate for ischaemic stroke per 100000 people increased(from 75.9 to 402.7,Ptrend<0.001),and the prevalence of risk factors,including hypertension,diabetes,dyslipidaemia and current smoking,increased.The composite score of diagnostic tests for stroke aetiology assessment(from 0.22 to 0.36,Ptrend<0.001)and secondary prevention treatments(from 0.46 to 0.70,Ptrend<0.001)were improved.A temporal decrease was found in discharge against medical advice(DAMA)(from 15.2%(95%CI 13.7%to 16.7%)to 8.6%(8.1%to 9.0%);adjusted Ptrend=0.046),and decreases in in-hospital mortality(0.7%in 2015 vs 1.8%in 2005;adjusted OR(aOR)0.52;95%CI 0.32 to 0.85)and the composite outcome of in-hospital mortality or DAMA(8.4%in 2015 vs 13.9%in 2005;aOR 0.65;95%CI 0.47 to 0.89)were observed.Disparities between rural and urban hospitals narrowed;however,disparities persisted in in-hospital management(brain MRI:rural-urban difference from−14.4%to−11.2%;cerebrovascular assessment:from−20.3%to−16.7%;clopidogrel:from−2.1%to−10.3%;anticoagulant for atrial fibrillation:from−10.9%to−8.2%)and in-hospital outcomes(DAMA:from 2.7%to 5.0%;composite outcome of in-hospital mortality or DAMA:from 2.4%to 4.6%).Conclusions From 2005 to 2015,improvements in hospital admission and in-hospital management for ischaemic stroke in China were found.A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed.Disparities between rural and urban hospitals generally narrowed but persisted.
基金This study was supported by grants from the National Natural Science Foundation of China grant,The Innovation Team Fund of the First Affiliated Hospital of Zhengzhou University and the National Natural Science Foundation of China
文摘Background: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients. Methods: We performed an open-label prospective study in genetically confirmed adult (〉18 years old) SCA3 patients. NGF was administered by intramuscular injection (18 μg once daily) fbr 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA). Results: Twenty-one SCA3 patients ( 10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77,57 ± 2.27) were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48± 2.40 to 6.30 ± 1.87 (P 〈 0.001 ). Subsections SARA scores also showed significant improvements in stance (P = 0.003), speech (P = 0.023), finger chase (P = 0.015), fast alternating hand movements (P = 0.009), and heel-shin slide (P = 0.001). Conclusions: Our preliminary data suggest that NGF may be effective in treating patients with SCA3.
文摘Background:The 9-hole peg test (9-HPT) and 10-meter walk test (10-MWT) are commonly used to test finger motor function and walking ability.The aim of this present study was to investigate the efficacy of these tests for evaluating functional loss in Chinese Charcot-Marie-Tooth (CMT) disease.Methods:Thirty-four Chinese CMT patients (CMT group) from August 2015 to December 2016 were evaluated with 9-HPT,10-MWT,CMT disease examination score,overall neuropathy limitation scale (ONLS),functional disability score,and Berg Balance Scale (BBS).Thirty-five age-and gender-matched healthy controls (control group) were also included in the study.Student's nonpaired or paired t-test were performed to compare data between two independent or related groups,respectively.The Pearson test was used to examine the correlations between recorded parameters.Results:The mean 9-HPT completion time in the dominant hand of CMT patients was significantly slower than that in the healthy controls (29.60 ± 11.89 s vs.19.58 ± 3.45 s;t =-4.728,P 〈 0.001).Women with CMT completed the 9-HPT significantly faster than men with CMT (dominant hand:24.74 ± 7.93 s vs.33.01 ± 13.14 s,t =2.097,P =0.044).The gait speed of the average self-selected velocity and the average fast-velocity assessed using 10-MWT for CMT patients were significantly slower than those in the control group (1.03 ± 0.18 m/s vs.1.44 ± 0.17 m/s,t =9.333,P 〈 0.001;1.31 ± 0.30 m/s vs.1.91 ± 0.25 m/s,t =8.853,P 〈 0.00 1,respectively).There was no difference in gait speed between men and women.Both 9-HPT and 10-MWT were significantly correlated with the ONLS,functional disability score,and BBS (P 〈 0.05 for all).Conclusion:The 9-HPT and 10-MWT might be useful for functional assessment in Chinese patients with CMT.
文摘Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.Additionally,white matter progression is an independent risk factor,which may be a potential therapeutic target.