Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve domi...Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles.A new method of ulnar nerve compound muscle action potential measurement was developed in 2020,which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist.This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential.In this prospective cross-sectional study,we included 64 patients with amyotrophic lateral sclerosis and 64 age-and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital.The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage.In the controls,no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings.In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy,the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2(P<0.01).Using the new method,damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method,in particular for patients in early stage amyotrophic lateral sclerosis.In addition,the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores.These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position,and that this method is more suitable for monitoring disease progression than the traditional montage.This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.展开更多
Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuropr...Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).展开更多
The dying-back hypothesis holds that the damage to neuromuscular junctions and distal axons in amyotrophic lateral sclerosis occurs at the earliest stage of the disease.Previous basic studies have confirmed early dama...The dying-back hypothesis holds that the damage to neuromuscular junctions and distal axons in amyotrophic lateral sclerosis occurs at the earliest stage of the disease.Previous basic studies have confirmed early damage to neuromuscular junctions,but it is difficult to obtain such evidence directly in clinical practice.In this prospective cross-sectional study,we recruited 22 patients with early amyotrophic lateral sclerosis with disease duration < 12 months and with clinical symptoms limited to the upper limbs.We also recruited 32 healthy controls.Repetitive nerve stimulation was performed,and patients were followed for 12 months.We found a significant change in the response to repetitive nerve stimulation in amyotrophic lateral sclerosis patients without spontaneous electromyographic activity.Patients that were prone to denervation had an increased decrement response of target muscles after repetitive nerve stimulation.These results suggest that changes in response to repetitive nerve stimulation may occur before denervation in amyotrophic lateral sclerosis patients.The damage to lower motor neurons is more obvious in patients with a higher percentage of repetitive never stimulation-related amplitude decrements.This study was approved by the Institutional Ethics Committee of Peking University Third Hospital(approval No.M2017198) on August 24,2017.展开更多
Objective:To compare the effect of surgical intervention on functional treatment.Methods: By searching the MEDLINE(1966 to October 2011),EMBASE(1980 to October 2011),the Chinese Biomedical Database Databases(1980 to O...Objective:To compare the effect of surgical intervention on functional treatment.Methods: By searching the MEDLINE(1966 to October 2011),EMBASE(1980 to October 2011),the Chinese Biomedical Database Databases(1980 to October 2011),a total of 9 related RCT studies comparing surgical intervention with functional treatment were included in our study.RevMan software was taken to analyze the data.Results:These 9 studies Involved a total of 1 268 mostly young adults,including 580 patients with surgical treatment and 688 patients with functional treatment.The results showed the stability of ankle activity in surgical treatment group was better than that in functional treatment group,with the OR and 95%CI of 0.72(0.52-0.99).No significant difference was found in the recurrence of the surgical and functional group.However, the movement disorder in the surgical treatment suggested increased risk than that in functional group,with the OR and 95%CI of 2 39(0.98-5.85).Surgical group found more complication than the function group,such as deep vein thrombosis,deep venous thrombosis,tenderness of scar and sensory loss.Conclusions:In conclusion,our finding showed that surgical treatment could gain better efficacy than functional treatment,but may bring more complication.Therefore,further large sample size RCT is warranted.展开更多
BACKGROUND Autosomal recessive spinocerebellar ataxia type 4(SCAR4)is a type of SCA that is a group of hereditary diseases characterized by gait ataxia.The main clinical features of SCAR4 are progressive cerebellar at...BACKGROUND Autosomal recessive spinocerebellar ataxia type 4(SCAR4)is a type of SCA that is a group of hereditary diseases characterized by gait ataxia.The main clinical features of SCAR4 are progressive cerebellar ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.To date,many gene dysfunctions have been reported to be associated with SCAR4.CASE SUMMARY Here,we report a novel compound heterozygous mutation,c.3288delA(p.Asp1097-ThrfsTer6),in the VPS13D gene in a young female Chinese patient.The patient found something wrong with her legs about 10 years ago and presented with the typical characteristics of SCAR4 when she came to the hospital,including ataxia,neuropathy,and positive pyramidal signs.She was then diagnosed with SCAR4 and went home with symptomatic schemes.CONCLUSION SCAR4 is a hereditary disease characterized by ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.We report a novel compound heterozygous mutation,c.3288delA(p.Asp1097ThrfsTer6),in the VPS13D gene,which enriches the gene mutation spectrum and provides additional information about SCAR4.展开更多
Background:Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS)in remission.The primary objective of the current analysis was to assess the efficacy and safety of two terifluno...Background:Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS)in remission.The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7mg and 14mg)in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods:TOWER was a multicenter,multinational,randomized, double-blind,parallel-group (three groups),placebo-controlled study.This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7mg (n =51), teriflunomide 14mg (n=43),or placebo (n=54). Results:Of the 148patients in the intent-to-treat population, adjusted annualized-relapse rates were 0.63(95% confidence interval [CI]:0.44,0.92)in the placebo group,0.48(95%CI:0.33, 0.70)in the teriflunomide 7mg group,and 0.18(95%CI:0.09,0.36)in the terifltmomide 14mg group;this corresponded to a significant relative risk reduction in the teriflunomide 14mg group versus placebo (-71.2%,P =0.0012).Terifiunomide 14mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio:0.319,P =0.1194).There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs;72.2% in the placebo group,74.5%in the teriflunomide 7mg group,and 69.8% in the teriflunomide 14mg group);corresponding proportions for serious adverse events were 11.1%,3.9%,and 11.6%,respectively.The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia,increased alanine aminotransferase,and hair thinning. Conclusions:Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial.Teriflunomide has the potential to meet unmet medical needs for MS patients in China.展开更多
The imbalance between β-amyloid(Aβ) generation and clearance plays a fundamental role in the pathogenesis of Alzheimer 's disease(AD). The sporadic form of AD is characterized by an overall impairment in Aβ cle...The imbalance between β-amyloid(Aβ) generation and clearance plays a fundamental role in the pathogenesis of Alzheimer 's disease(AD). The sporadic form of AD is characterized by an overall impairment in Aβ clearance. Immunotherapy targeting Aβ clearance is believed to be a promising approach and is under active clinical investigation. Autophagy is a conserved pathway for degrading abnormal protein aggregates and is crucial for Aβ clearance. We previously reported that oral vaccination with a recombinant AAV/Aβ vaccine increased the clearance of Aβ from the brain and improved cognitive ability in AD animal models, while the underlying mechanisms were not well understood. In this study, we first demonstrated that oral vaccination with rAAV/Aβ decreased the p62 level and up-regulated the LC3BII/LC3B-I ratio in APP/PS1 mouse brain, suggesting enhanced autophagy. Further, inhibition of the Akt/m TOR pathway may account for autophagy enhancement. We also found increased anti-Aβ antibodies in the sera of APP/PS1 mice with oralvaccination, accompanied by elevation of complement factors C1 q and C3 levels in the brain. Our results indicate that autophagy is closely involved in oral vaccination-induced Aβ clearance, and modulating the autophagy pathway may be an important strategy for AD prevention and intervention.展开更多
Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer's disease(AD). Furthermore, it is also well accepted that some inhalation anesthetics, such as isofl...Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer's disease(AD). Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause ADlike neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocampal autophagy in aged rats. Aged Sprague-Dawley rats(20 months old) were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze(4 trials/day for 5 consecutive days). Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B(LC3B), as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3 BII, and p62 at 24 h post-anesthesia between the1-h isoflurane-exposed rats and their controls(P >0.05). Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 postanesthesia and less time spent in the target quadrant than sham-exposed animals(P <0.05). These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane(P <0.01 and P <0.05). Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease w ithin 12–24 h post-anesthesia(P <0.05). Hippocampal p62 p eaked at 6 h but subsequently resolved. These results from our pilot in vivo study support a durationdependent relationship between 1.5% isoflurane exposure, and s patial cognitive function as well as hippocampal phagophore formation.展开更多
To the Editor:Distal myopathy is a heterogenetic disorder characterized by early distal lower limb involvement,which has been linked to 18 disease-causing genes.The gene responsible for Laing distal myopathy(LDM,also ...To the Editor:Distal myopathy is a heterogenetic disorder characterized by early distal lower limb involvement,which has been linked to 18 disease-causing genes.The gene responsible for Laing distal myopathy(LDM,also called distal myopathy 1;OMIM 160500)was determined to be the myosin heavy chain 7 gene(MYH7)located on chromosome 14q11.[1] MYH7 encodes the myosin heavy chain beta isoform(MyHC-β)and is expressed predominantly in the cardiac ventricle and in type 1 skeletal muscle fibers.展开更多
Background:SOD1 mutations are the most common cause of amyotrophic lateral sclerosis(ALS)in non-Caucasian patients.Detailed natural history profiles of SOD1-mutant patients will be beneficial for the strategy and inte...Background:SOD1 mutations are the most common cause of amyotrophic lateral sclerosis(ALS)in non-Caucasian patients.Detailed natural history profiles of SOD1-mutant patients will be beneficial for the strategy and interpretation of future SOD1-targeted clinical practice.Methods:Mutational distribution,age at onset(AAO),site of onset,diagnostic delay,disease progression(rate of ALSFRS-R decrease,ΔFS)and survival were analysed.Further comparisons between heredity of disease,gender,and mutations were performed.Results:Sixty-six cases with 43 SOD1 mutations were included and analysed,with p.His47Arg as the leading mutation and seven novel variants identified.The mean(SD)AAO was 43.92 years(9.24)for all subjects,with a significant difference between patients carrying mutations in exon 2(n=24,46.83,8.31)and exon 4(n=18,37.75,7.67)(p=0.002).The median(IQR)diagnostic delay from symptom onset was 14.50(6.00–36.50)months for all SOD1-mutant patients,9.50(4.75–24.25)months for males and 24.00(9.50–47.50)months for females,revealing a gender difference(p=0.009).Similar advantages in median(IQR)ΔFS[male:female,0.55(0.24–0.94)vs 0.19(0.06–0.90),p=0.041]and mean(95%CI)survival[57.4(38.90–75.90)months vs 125.6(99.80–151.50)months,p=0.006]were also observed in females,both of which existed in sporadic ALS only when stratified by familiar or sporadic ALS.Conclusions:The results highlight a distinct mutational distribution and natural history spectrum in ALS patients carrying SOD1 mutations in China.A prominent mild disease progression was observed in female patients,which had rarely been reported in the previous literature.This finding,together with the detailed analysis of natural history among each mutation,can have important implications for future genetic counselling and SOD1-targeted clinical trials.展开更多
To the Editor:A 39-year-old man presented with progressive limb atrophy and weakness.The patient had generalized muscular hypotonia at birth;he could not run well in elementary school.Neurologic examination revealed a...To the Editor:A 39-year-old man presented with progressive limb atrophy and weakness.The patient had generalized muscular hypotonia at birth;he could not run well in elementary school.Neurologic examination revealed atrophy of the facial muscles and limited left eye adduction.In the upper limbs,the patients showed proximal muscle atrophy and weakness[Figure 1A],while in the lower extremities,the weakness was more prominent distally than proximally.Neither spontaneous or percussion myotonia nor muscle hypertrophy was observed.展开更多
To the Editor:Motor neuron disease(MND)is a kind of progressive,fatal neurodegenerative disease involving the upper and lower motor neurons and the pyramidal tract.Currently,the etiology of MND remains unknown,and the...To the Editor:Motor neuron disease(MND)is a kind of progressive,fatal neurodegenerative disease involving the upper and lower motor neurons and the pyramidal tract.Currently,the etiology of MND remains unknown,and there are limited treatment strategies.Paraneoplastic syndrome(PNS)is a rare form of MND-mimic syndrome.There have been reports of MND-like clinical symptoms in patients with different types of cancer,including breast cancer,lung cancer,and lymphoma.Epidemiological studies have drawn different conclusions,some have suggested that there is no relation between site-specific cancers and the risk of incident amyotrophic lateral sclerosis(ALS),while others have found that the overall risk of cancer of any site is significantly reduced in cases with ALS.[1]However,the prevalence of tumors in Chinese MND patients and the characteristics of patients with MND concomitant tumors are unclear.展开更多
In the original publication of this article[1],a numerical value in the sentence“The mean(SD)AAO was 43.92 years(9.24)for all subjects,with a significant difference between patients carrying mutations in exon 2(n=24,...In the original publication of this article[1],a numerical value in the sentence“The mean(SD)AAO was 43.92 years(9.24)for all subjects,with a significant difference between patients carrying mutations in exon 2(n=24,46.83,8.31)and exon 4(n=18,37.75,7.67)(p=0.002).”is wrong.The true value in the parenthesis of exon 2 should be(n=24,46.63,8.31).展开更多
基金supported by the National Natural Science Foundation of China,Nos.81873784,82071426Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DSF)。
文摘Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles.A new method of ulnar nerve compound muscle action potential measurement was developed in 2020,which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist.This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential.In this prospective cross-sectional study,we included 64 patients with amyotrophic lateral sclerosis and 64 age-and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital.The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage.In the controls,no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings.In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy,the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2(P<0.01).Using the new method,damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method,in particular for patients in early stage amyotrophic lateral sclerosis.In addition,the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores.These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position,and that this method is more suitable for monitoring disease progression than the traditional montage.This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.
文摘Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).
文摘The dying-back hypothesis holds that the damage to neuromuscular junctions and distal axons in amyotrophic lateral sclerosis occurs at the earliest stage of the disease.Previous basic studies have confirmed early damage to neuromuscular junctions,but it is difficult to obtain such evidence directly in clinical practice.In this prospective cross-sectional study,we recruited 22 patients with early amyotrophic lateral sclerosis with disease duration < 12 months and with clinical symptoms limited to the upper limbs.We also recruited 32 healthy controls.Repetitive nerve stimulation was performed,and patients were followed for 12 months.We found a significant change in the response to repetitive nerve stimulation in amyotrophic lateral sclerosis patients without spontaneous electromyographic activity.Patients that were prone to denervation had an increased decrement response of target muscles after repetitive nerve stimulation.These results suggest that changes in response to repetitive nerve stimulation may occur before denervation in amyotrophic lateral sclerosis patients.The damage to lower motor neurons is more obvious in patients with a higher percentage of repetitive never stimulation-related amplitude decrements.This study was approved by the Institutional Ethics Committee of Peking University Third Hospital(approval No.M2017198) on August 24,2017.
文摘Objective:To compare the effect of surgical intervention on functional treatment.Methods: By searching the MEDLINE(1966 to October 2011),EMBASE(1980 to October 2011),the Chinese Biomedical Database Databases(1980 to October 2011),a total of 9 related RCT studies comparing surgical intervention with functional treatment were included in our study.RevMan software was taken to analyze the data.Results:These 9 studies Involved a total of 1 268 mostly young adults,including 580 patients with surgical treatment and 688 patients with functional treatment.The results showed the stability of ankle activity in surgical treatment group was better than that in functional treatment group,with the OR and 95%CI of 0.72(0.52-0.99).No significant difference was found in the recurrence of the surgical and functional group.However, the movement disorder in the surgical treatment suggested increased risk than that in functional group,with the OR and 95%CI of 2 39(0.98-5.85).Surgical group found more complication than the function group,such as deep vein thrombosis,deep venous thrombosis,tenderness of scar and sensory loss.Conclusions:In conclusion,our finding showed that surgical treatment could gain better efficacy than functional treatment,but may bring more complication.Therefore,further large sample size RCT is warranted.
文摘BACKGROUND Autosomal recessive spinocerebellar ataxia type 4(SCAR4)is a type of SCA that is a group of hereditary diseases characterized by gait ataxia.The main clinical features of SCAR4 are progressive cerebellar ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.To date,many gene dysfunctions have been reported to be associated with SCAR4.CASE SUMMARY Here,we report a novel compound heterozygous mutation,c.3288delA(p.Asp1097-ThrfsTer6),in the VPS13D gene in a young female Chinese patient.The patient found something wrong with her legs about 10 years ago and presented with the typical characteristics of SCAR4 when she came to the hospital,including ataxia,neuropathy,and positive pyramidal signs.She was then diagnosed with SCAR4 and went home with symptomatic schemes.CONCLUSION SCAR4 is a hereditary disease characterized by ataxia,pyramidal signs,neuropathy,and macrosaccadic intrusions.We report a novel compound heterozygous mutation,c.3288delA(p.Asp1097ThrfsTer6),in the VPS13D gene,which enriches the gene mutation spectrum and provides additional information about SCAR4.
文摘Background:Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS)in remission.The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7mg and 14mg)in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods:TOWER was a multicenter,multinational,randomized, double-blind,parallel-group (three groups),placebo-controlled study.This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7mg (n =51), teriflunomide 14mg (n=43),or placebo (n=54). Results:Of the 148patients in the intent-to-treat population, adjusted annualized-relapse rates were 0.63(95% confidence interval [CI]:0.44,0.92)in the placebo group,0.48(95%CI:0.33, 0.70)in the teriflunomide 7mg group,and 0.18(95%CI:0.09,0.36)in the terifltmomide 14mg group;this corresponded to a significant relative risk reduction in the teriflunomide 14mg group versus placebo (-71.2%,P =0.0012).Terifiunomide 14mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio:0.319,P =0.1194).There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs;72.2% in the placebo group,74.5%in the teriflunomide 7mg group,and 69.8% in the teriflunomide 14mg group);corresponding proportions for serious adverse events were 11.1%,3.9%,and 11.6%,respectively.The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia,increased alanine aminotransferase,and hair thinning. Conclusions:Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial.Teriflunomide has the potential to meet unmet medical needs for MS patients in China.
基金supported by the National Basic Research Development Program of China(2012CB911000 and 2012CB911004)the NSFC-JSPS Cooperation Program (81211140047)the National Natural Science Foundation of China(81171015)
文摘The imbalance between β-amyloid(Aβ) generation and clearance plays a fundamental role in the pathogenesis of Alzheimer 's disease(AD). The sporadic form of AD is characterized by an overall impairment in Aβ clearance. Immunotherapy targeting Aβ clearance is believed to be a promising approach and is under active clinical investigation. Autophagy is a conserved pathway for degrading abnormal protein aggregates and is crucial for Aβ clearance. We previously reported that oral vaccination with a recombinant AAV/Aβ vaccine increased the clearance of Aβ from the brain and improved cognitive ability in AD animal models, while the underlying mechanisms were not well understood. In this study, we first demonstrated that oral vaccination with rAAV/Aβ decreased the p62 level and up-regulated the LC3BII/LC3B-I ratio in APP/PS1 mouse brain, suggesting enhanced autophagy. Further, inhibition of the Akt/m TOR pathway may account for autophagy enhancement. We also found increased anti-Aβ antibodies in the sera of APP/PS1 mice with oralvaccination, accompanied by elevation of complement factors C1 q and C3 levels in the brain. Our results indicate that autophagy is closely involved in oral vaccination-induced Aβ clearance, and modulating the autophagy pathway may be an important strategy for AD prevention and intervention.
基金supported by grants from the National Natural Science Foundation of China (81371205)the National Basic Research Development Program (973 Program) of China (2012CB911000 and 2012CB911004)
文摘Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer's disease(AD). Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause ADlike neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocampal autophagy in aged rats. Aged Sprague-Dawley rats(20 months old) were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze(4 trials/day for 5 consecutive days). Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B(LC3B), as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3 BII, and p62 at 24 h post-anesthesia between the1-h isoflurane-exposed rats and their controls(P >0.05). Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 postanesthesia and less time spent in the target quadrant than sham-exposed animals(P <0.05). These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane(P <0.01 and P <0.05). Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease w ithin 12–24 h post-anesthesia(P <0.05). Hippocampal p62 p eaked at 6 h but subsequently resolved. These results from our pilot in vivo study support a durationdependent relationship between 1.5% isoflurane exposure, and s patial cognitive function as well as hippocampal phagophore formation.
文摘To the Editor:Distal myopathy is a heterogenetic disorder characterized by early distal lower limb involvement,which has been linked to 18 disease-causing genes.The gene responsible for Laing distal myopathy(LDM,also called distal myopathy 1;OMIM 160500)was determined to be the myosin heavy chain 7 gene(MYH7)located on chromosome 14q11.[1] MYH7 encodes the myosin heavy chain beta isoform(MyHC-β)and is expressed predominantly in the cardiac ventricle and in type 1 skeletal muscle fibers.
基金This work was supported by the National Natural Science Foundation of China under Grant 81030019Peking University-Ulm University Union Foundation under Grant PKU2017ZC001-2+1 种基金the Natural Science Foundation of Beijing Municipality under Grant 7102161the National Clinical Key Program of China.
文摘Background:SOD1 mutations are the most common cause of amyotrophic lateral sclerosis(ALS)in non-Caucasian patients.Detailed natural history profiles of SOD1-mutant patients will be beneficial for the strategy and interpretation of future SOD1-targeted clinical practice.Methods:Mutational distribution,age at onset(AAO),site of onset,diagnostic delay,disease progression(rate of ALSFRS-R decrease,ΔFS)and survival were analysed.Further comparisons between heredity of disease,gender,and mutations were performed.Results:Sixty-six cases with 43 SOD1 mutations were included and analysed,with p.His47Arg as the leading mutation and seven novel variants identified.The mean(SD)AAO was 43.92 years(9.24)for all subjects,with a significant difference between patients carrying mutations in exon 2(n=24,46.83,8.31)and exon 4(n=18,37.75,7.67)(p=0.002).The median(IQR)diagnostic delay from symptom onset was 14.50(6.00–36.50)months for all SOD1-mutant patients,9.50(4.75–24.25)months for males and 24.00(9.50–47.50)months for females,revealing a gender difference(p=0.009).Similar advantages in median(IQR)ΔFS[male:female,0.55(0.24–0.94)vs 0.19(0.06–0.90),p=0.041]and mean(95%CI)survival[57.4(38.90–75.90)months vs 125.6(99.80–151.50)months,p=0.006]were also observed in females,both of which existed in sporadic ALS only when stratified by familiar or sporadic ALS.Conclusions:The results highlight a distinct mutational distribution and natural history spectrum in ALS patients carrying SOD1 mutations in China.A prominent mild disease progression was observed in female patients,which had rarely been reported in the previous literature.This finding,together with the detailed analysis of natural history among each mutation,can have important implications for future genetic counselling and SOD1-targeted clinical trials.
文摘To the Editor:A 39-year-old man presented with progressive limb atrophy and weakness.The patient had generalized muscular hypotonia at birth;he could not run well in elementary school.Neurologic examination revealed atrophy of the facial muscles and limited left eye adduction.In the upper limbs,the patients showed proximal muscle atrophy and weakness[Figure 1A],while in the lower extremities,the weakness was more prominent distally than proximally.Neither spontaneous or percussion myotonia nor muscle hypertrophy was observed.
基金National Natural Sciences Foundation of China(No.81873784)。
文摘To the Editor:Motor neuron disease(MND)is a kind of progressive,fatal neurodegenerative disease involving the upper and lower motor neurons and the pyramidal tract.Currently,the etiology of MND remains unknown,and there are limited treatment strategies.Paraneoplastic syndrome(PNS)is a rare form of MND-mimic syndrome.There have been reports of MND-like clinical symptoms in patients with different types of cancer,including breast cancer,lung cancer,and lymphoma.Epidemiological studies have drawn different conclusions,some have suggested that there is no relation between site-specific cancers and the risk of incident amyotrophic lateral sclerosis(ALS),while others have found that the overall risk of cancer of any site is significantly reduced in cases with ALS.[1]However,the prevalence of tumors in Chinese MND patients and the characteristics of patients with MND concomitant tumors are unclear.
文摘In the original publication of this article[1],a numerical value in the sentence“The mean(SD)AAO was 43.92 years(9.24)for all subjects,with a significant difference between patients carrying mutations in exon 2(n=24,46.83,8.31)and exon 4(n=18,37.75,7.67)(p=0.002).”is wrong.The true value in the parenthesis of exon 2 should be(n=24,46.63,8.31).
