Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
BACKGROUND Orbital hemorrhage can be classified as traumatic or spontaneous depending on its cause.Spontaneous orbital hemorrhage refers to an internal orbital hemorrhage without apparent cause.Therefore,we aimed to d...BACKGROUND Orbital hemorrhage can be classified as traumatic or spontaneous depending on its cause.Spontaneous orbital hemorrhage refers to an internal orbital hemorrhage without apparent cause.Therefore,we aimed to describe a case of an orbital hematoma after a severe cough the night before due to inhalation of cooking oil fumes.CASE SUMMARY A 46-year-old woman was referred to our hospital with a complaint of exophthalmos accompanied with blurred vision,pain,binocular diplopia,and dizziness lasting for 5 h noted on waking in the morning.She also experienced nausea and vomiting due to high pressure of orbit and dizziness.Based on the auxiliary examination and her medical history,the patient was finally diagnosed with bulbar conjunctival vascular lesion combined with spontaneous retrobulbar hematoma.The patient was administered tobramycin and dexamethasone eye ointment,and applied pressure dressing on the left eye to stop the bleeding.Simultaneously,we administered intravenous etamsylate,oral Yunnan Baiyao capsule,intravenous mannitol to reduce orbital pressure,and intravenous dexamethasone injection at 10 mg/dL combined with neurotrophic therapy to reduce tissue edema.Among them,the Yunnan Baiyao capsule is a traditional Chinese herbal medicine to remove stasis and stop bleeding;thus,it promotes blood circulation and relieves pain resulting in reduced edema of the lesion site.The symptoms did not improve significantly during the first 2 d of treatment.We speculate that high orbital pressure and binocular diplopia induced frequent nausea and vomiting in the patient,causing increased pressure on the superior vena cava and leading to repeated orbital bleeding.After the second day,the symptoms started gradually improving.CONCLUSION This case further emphasizes the importance of comprehensive,detailed medical history and careful ophthalmic examination of the patient.展开更多
Objectives: To report the 2-years follow-up of patients with bulbar urethral strictures treated with the new AlliumTM Bulbar Urethral Stent (Allium BUS). Methods: The stent is a fully covered, self-expendable, large c...Objectives: To report the 2-years follow-up of patients with bulbar urethral strictures treated with the new AlliumTM Bulbar Urethral Stent (Allium BUS). Methods: The stent is a fully covered, self-expendable, large caliber metal stent specially designed for the treatment of bulbar urethral strictures. The stent is comprised of a coiled super-elastic structure covered by a polymeric coating designed to prevent mucosal hyperplasia. The indwelling time is 12 months, after which the stent should have been removed. Sixty-four patients with recurrent bulbar stricture were treated with Allium BUS in 3 worldwide centers. Results: All stents were successfully inserted with no perioperative complications. In a median follow-up of 25.5 months, the mean maximal flow rate following stent insertion was significantly higher compared to the pre-surgical flow rate (14 ml/sec vs 6.6 ml/sec, p < 0.0001). Longer indwelling time and shorter stricture length were significantly related to success rate. The main complications were stent migration, stent re-stenosis and urinary tract infections. Conclusions: The temporary placement of the AlliumTM BUS showed encouraging results with long-term failure rate of only 25%.展开更多
Background：Progressive bulbar palsy （PBP） is a classic phenotype ofbulbar onset amyotrophic lateral sclerosis （ALS） with more rapid progression and worse prognosis.However,as an often under-understood variant of ...Background：Progressive bulbar palsy （PBP） is a classic phenotype ofbulbar onset amyotrophic lateral sclerosis （ALS） with more rapid progression and worse prognosis.However,as an often under-understood variant of ALS,isolated bulbar palsy （IBP） appears to progress more slowly and has a relatively benign prognosis.This study aimed to investigate the natural course and clinical features of IBP in Chinese population and to compare them with those of PBP.Methods：The clinical data of patients with bulbar onset ALS were collected from January 2009 to December 2013.Revised ALS Functional Rating Scale （ALSFRS-R）,forced vital capacity （FVC）,and follow-up evaluation were performed,and the differences in basic clinical features,ALSFRS-R,FVC,and primary outcome measures between IBP and PBP were analyzed.The independent t-test,Chi-square test,Mann-Whitney U-test,and Kaplan-Meier analysis were used.Results：Totally 154 patients with bulbar onset ALS were categorized into two groups,33 with IBP and 121 with PBP.In the IBP group,the male to female ratio was 0.7 to 1.0,and the mean onset age was 58.5 years.The mean duration from the onset was 16.0 months,and the mean ALSFRS-R score was 43.4 at patients＇ first visit to our hospital.In 14 IBP patients performing FVC examination,the mean FVC value was 90.5% and there were only two cases with abnormal FVC.In 26 IBP patients completing follow-up,15 （58%） suffered death or tracheotomy and the mean survival time was 40.5 months.Significant differences were noted in sex ratio,onset age,ALSFRS-R score,upper motor neuron limb signs,pure lower motor neuron （LMN） bulbar signs,FVC,and survival time between IBP and PBP.Conclusions：IBP was evidently different from PBP.which was characterized with the predominance of female,pure LMN bulbar signs,an older onset age,a relative preservation of respiratory function,and a better prognosis.展开更多
Objective： To investigate the factors influencing the therapeutic effect in acupuncture treatment of apoplectic pseudobulbar palsy （PBP）. Methods： Sixty patients with apoplectic pseudobulbar palsy in pattern of ob...Objective： To investigate the factors influencing the therapeutic effect in acupuncture treatment of apoplectic pseudobulbar palsy （PBP）. Methods： Sixty patients with apoplectic pseudobulbar palsy in pattern of obstruction of wind and phlegm in the meridians were randomly divided into the treatment group and control group, to observe the therapeutic effect. Results and Conclusion： The therapeutic effect was significantly better in the treatment group than in the control group （P〈0.05）. It has been found in the study that with increase in the occurrence of cerebral apoplexy, the incidence rate of severe dysphagia increased and dysphagia took place progressively earlier, indicating the importance of early treatment and prevention of cerebral apoplexy.展开更多
Bulbar urethral ischemic necrosis(BUIN)is an iatrogenic entity resulting from repeated attempts at performing anastomotic urethroplasty for pelvic fracture urethral injuries.Etiologically speaking,BUIN is related to a...Bulbar urethral ischemic necrosis(BUIN)is an iatrogenic entity resulting from repeated attempts at performing anastomotic urethroplasty for pelvic fracture urethral injuries.Etiologically speaking,BUIN is related to a compromised blood supply of the bulbar urethra,which normally relies on anterograde supply from bulbar arteries and retrograde supply from recurrent branches of dorsal penile arteries,through the glans.At each transection of the bulbar urethra,both the anterograde and retrograde supplies are compromised,increasing the risk of BUIN.Even though this term is widely used among reconstructive urologists,BUIN is orphan of an accepted scientific definition.We aim to report our personal perspective on BUIN,to identify factors associated with its occurrence,and to describe the management options in these patients.展开更多
目的探讨肌萎缩侧索硬化症(amyotrophy lateral sclerosis,ALS)患者初级运动皮层(primary motor cortex,PMC)的face-head区域皮质厚度变化特点及对生存期的影响。方法对同时行头颅MRI扫描的105例ALS患者回顾性分析,PMC区A4hf(face-head...目的探讨肌萎缩侧索硬化症(amyotrophy lateral sclerosis,ALS)患者初级运动皮层(primary motor cortex,PMC)的face-head区域皮质厚度变化特点及对生存期的影响。方法对同时行头颅MRI扫描的105例ALS患者回顾性分析,PMC区A4hf(face-head)区域作为兴趣区域(region of interest,ROI),根据患者临床症状分为延髓受累和未受累两组,分析临床特点和ROI区域的皮质厚度在两组间的差异;根据患者延髓麻痹症状、神经系统查体和舌肌肌电图,将延髓受累ALS分为下运动神经元(lower motor neuron,LMN)、上运动神经元(upper motor neuron,UMN)和LMN+UMN共3组,分析延髓亚组评分和ROI皮质厚度在3组间的差异;将起病年龄、体质量指数、诊断延迟时间、延髓亚组评分和ROI皮质厚度纳入生存分析。结果①延髓受累组ROI皮质厚度明显小于延髓未受累组(-0.198±0.87 vs.0.235±0.95,P=0.017);②延髓亚组评分和ROI皮质厚度在LMN、UMN和LMN+UMN三组间无统计学差异(P>0.05);③生存分析示起病年龄(HR=3.296,95%CI:1.63~6.664,P=0.001)、诊断延迟时间(HR=0.361,95%CI:0.184~0.705,P=0.003)、延髓亚组评分(HR=0.389,95%CI:0.174~0.868,P=0.021)及ZRE_ROI皮质厚度(HR=2.309,95%CI:1.046~5.096,P=0.038)均是ALS患者生存期的独立影响因素。结论大脑运动前回A4hf(face-head)区域的皮质厚度可更为客观反映延髓UMN体征。影响ALS患者生存期的因素除了起病年龄和诊断延迟时间,延髓亚组评分和face-head区域的皮质厚度也是其独立影响因素,且face-head区域皮质变薄是ALS患者生存期的保护因素。展开更多
Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immun...Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immunocompromised individuals and the elderly, particularly those with a history of diabetes mellitus. Diagnosis is challenging because of non-specific symptoms that lead to late detection and complications. This report discusses a case of SBO with multiple bilateral cranial nerve abnormalities and highlights the diagnostic and management challenges in high-risk individuals with subtle clinical signs. Case presentation: This report describes a 63-year-old patient with hypertension and diabetes who underwent surgical debridement of the left ear due to malignant otitis externa 4 months prior to presentation. The patient presented with significant dysarthria, dysphagia, ptosis of the left eye with double vision, and hearing impairment in the left ear. Examination revealed bilateral CN VI palsy, right CN VII palsy, left CN VIII palsy, and a right CN XII deficit. Initial tests were unremarkable, but a high Fungitell assay and a second review of the CT scan and MRI revealed a pathological process in the base of the skull involving bony structures and cranial nerves bilaterally, which helped diagnose SBO. The patient was subsequently discharged with oral voriconazole and continued his usual medications. The patient requested further management abroad, because he did not notice resolution of his symptoms. Surgical treatment was employed abroad to relieve his symptoms, as he recovered slowly. Conclusion: This case report underscores the importance of a multidisciplinary approach to address SBO. Collaboration between specialists in infectious diseases, otolaryngology, radiology, and neurology plays a pivotal role in achieving an accurate diagnosis and developing a tailored treatment plan. Although SBO may be infrequent, this case report highlights the need to maintain heightened clinical suspicion in high-risk individuals.展开更多
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
文摘BACKGROUND Orbital hemorrhage can be classified as traumatic or spontaneous depending on its cause.Spontaneous orbital hemorrhage refers to an internal orbital hemorrhage without apparent cause.Therefore,we aimed to describe a case of an orbital hematoma after a severe cough the night before due to inhalation of cooking oil fumes.CASE SUMMARY A 46-year-old woman was referred to our hospital with a complaint of exophthalmos accompanied with blurred vision,pain,binocular diplopia,and dizziness lasting for 5 h noted on waking in the morning.She also experienced nausea and vomiting due to high pressure of orbit and dizziness.Based on the auxiliary examination and her medical history,the patient was finally diagnosed with bulbar conjunctival vascular lesion combined with spontaneous retrobulbar hematoma.The patient was administered tobramycin and dexamethasone eye ointment,and applied pressure dressing on the left eye to stop the bleeding.Simultaneously,we administered intravenous etamsylate,oral Yunnan Baiyao capsule,intravenous mannitol to reduce orbital pressure,and intravenous dexamethasone injection at 10 mg/dL combined with neurotrophic therapy to reduce tissue edema.Among them,the Yunnan Baiyao capsule is a traditional Chinese herbal medicine to remove stasis and stop bleeding;thus,it promotes blood circulation and relieves pain resulting in reduced edema of the lesion site.The symptoms did not improve significantly during the first 2 d of treatment.We speculate that high orbital pressure and binocular diplopia induced frequent nausea and vomiting in the patient,causing increased pressure on the superior vena cava and leading to repeated orbital bleeding.After the second day,the symptoms started gradually improving.CONCLUSION This case further emphasizes the importance of comprehensive,detailed medical history and careful ophthalmic examination of the patient.
文摘Objectives: To report the 2-years follow-up of patients with bulbar urethral strictures treated with the new AlliumTM Bulbar Urethral Stent (Allium BUS). Methods: The stent is a fully covered, self-expendable, large caliber metal stent specially designed for the treatment of bulbar urethral strictures. The stent is comprised of a coiled super-elastic structure covered by a polymeric coating designed to prevent mucosal hyperplasia. The indwelling time is 12 months, after which the stent should have been removed. Sixty-four patients with recurrent bulbar stricture were treated with Allium BUS in 3 worldwide centers. Results: All stents were successfully inserted with no perioperative complications. In a median follow-up of 25.5 months, the mean maximal flow rate following stent insertion was significantly higher compared to the pre-surgical flow rate (14 ml/sec vs 6.6 ml/sec, p < 0.0001). Longer indwelling time and shorter stricture length were significantly related to success rate. The main complications were stent migration, stent re-stenosis and urinary tract infections. Conclusions: The temporary placement of the AlliumTM BUS showed encouraging results with long-term failure rate of only 25%.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81030019）.
文摘Background：Progressive bulbar palsy （PBP） is a classic phenotype ofbulbar onset amyotrophic lateral sclerosis （ALS） with more rapid progression and worse prognosis.However,as an often under-understood variant of ALS,isolated bulbar palsy （IBP） appears to progress more slowly and has a relatively benign prognosis.This study aimed to investigate the natural course and clinical features of IBP in Chinese population and to compare them with those of PBP.Methods：The clinical data of patients with bulbar onset ALS were collected from January 2009 to December 2013.Revised ALS Functional Rating Scale （ALSFRS-R）,forced vital capacity （FVC）,and follow-up evaluation were performed,and the differences in basic clinical features,ALSFRS-R,FVC,and primary outcome measures between IBP and PBP were analyzed.The independent t-test,Chi-square test,Mann-Whitney U-test,and Kaplan-Meier analysis were used.Results：Totally 154 patients with bulbar onset ALS were categorized into two groups,33 with IBP and 121 with PBP.In the IBP group,the male to female ratio was 0.7 to 1.0,and the mean onset age was 58.5 years.The mean duration from the onset was 16.0 months,and the mean ALSFRS-R score was 43.4 at patients＇ first visit to our hospital.In 14 IBP patients performing FVC examination,the mean FVC value was 90.5% and there were only two cases with abnormal FVC.In 26 IBP patients completing follow-up,15 （58%） suffered death or tracheotomy and the mean survival time was 40.5 months.Significant differences were noted in sex ratio,onset age,ALSFRS-R score,upper motor neuron limb signs,pure lower motor neuron （LMN） bulbar signs,FVC,and survival time between IBP and PBP.Conclusions：IBP was evidently different from PBP.which was characterized with the predominance of female,pure LMN bulbar signs,an older onset age,a relative preservation of respiratory function,and a better prognosis.
文摘Objective： To investigate the factors influencing the therapeutic effect in acupuncture treatment of apoplectic pseudobulbar palsy （PBP）. Methods： Sixty patients with apoplectic pseudobulbar palsy in pattern of obstruction of wind and phlegm in the meridians were randomly divided into the treatment group and control group, to observe the therapeutic effect. Results and Conclusion： The therapeutic effect was significantly better in the treatment group than in the control group （P〈0.05）. It has been found in the study that with increase in the occurrence of cerebral apoplexy, the incidence rate of severe dysphagia increased and dysphagia took place progressively earlier, indicating the importance of early treatment and prevention of cerebral apoplexy.
文摘Bulbar urethral ischemic necrosis(BUIN)is an iatrogenic entity resulting from repeated attempts at performing anastomotic urethroplasty for pelvic fracture urethral injuries.Etiologically speaking,BUIN is related to a compromised blood supply of the bulbar urethra,which normally relies on anterograde supply from bulbar arteries and retrograde supply from recurrent branches of dorsal penile arteries,through the glans.At each transection of the bulbar urethra,both the anterograde and retrograde supplies are compromised,increasing the risk of BUIN.Even though this term is widely used among reconstructive urologists,BUIN is orphan of an accepted scientific definition.We aim to report our personal perspective on BUIN,to identify factors associated with its occurrence,and to describe the management options in these patients.
文摘目的探讨肌萎缩侧索硬化症(amyotrophy lateral sclerosis,ALS)患者初级运动皮层(primary motor cortex,PMC)的face-head区域皮质厚度变化特点及对生存期的影响。方法对同时行头颅MRI扫描的105例ALS患者回顾性分析,PMC区A4hf(face-head)区域作为兴趣区域(region of interest,ROI),根据患者临床症状分为延髓受累和未受累两组,分析临床特点和ROI区域的皮质厚度在两组间的差异;根据患者延髓麻痹症状、神经系统查体和舌肌肌电图,将延髓受累ALS分为下运动神经元(lower motor neuron,LMN)、上运动神经元(upper motor neuron,UMN)和LMN+UMN共3组,分析延髓亚组评分和ROI皮质厚度在3组间的差异;将起病年龄、体质量指数、诊断延迟时间、延髓亚组评分和ROI皮质厚度纳入生存分析。结果①延髓受累组ROI皮质厚度明显小于延髓未受累组(-0.198±0.87 vs.0.235±0.95,P=0.017);②延髓亚组评分和ROI皮质厚度在LMN、UMN和LMN+UMN三组间无统计学差异(P>0.05);③生存分析示起病年龄(HR=3.296,95%CI:1.63~6.664,P=0.001)、诊断延迟时间(HR=0.361,95%CI:0.184~0.705,P=0.003)、延髓亚组评分(HR=0.389,95%CI:0.174~0.868,P=0.021)及ZRE_ROI皮质厚度(HR=2.309,95%CI:1.046~5.096,P=0.038)均是ALS患者生存期的独立影响因素。结论大脑运动前回A4hf(face-head)区域的皮质厚度可更为客观反映延髓UMN体征。影响ALS患者生存期的因素除了起病年龄和诊断延迟时间,延髓亚组评分和face-head区域的皮质厚度也是其独立影响因素,且face-head区域皮质变薄是ALS患者生存期的保护因素。
文摘Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immunocompromised individuals and the elderly, particularly those with a history of diabetes mellitus. Diagnosis is challenging because of non-specific symptoms that lead to late detection and complications. This report discusses a case of SBO with multiple bilateral cranial nerve abnormalities and highlights the diagnostic and management challenges in high-risk individuals with subtle clinical signs. Case presentation: This report describes a 63-year-old patient with hypertension and diabetes who underwent surgical debridement of the left ear due to malignant otitis externa 4 months prior to presentation. The patient presented with significant dysarthria, dysphagia, ptosis of the left eye with double vision, and hearing impairment in the left ear. Examination revealed bilateral CN VI palsy, right CN VII palsy, left CN VIII palsy, and a right CN XII deficit. Initial tests were unremarkable, but a high Fungitell assay and a second review of the CT scan and MRI revealed a pathological process in the base of the skull involving bony structures and cranial nerves bilaterally, which helped diagnose SBO. The patient was subsequently discharged with oral voriconazole and continued his usual medications. The patient requested further management abroad, because he did not notice resolution of his symptoms. Surgical treatment was employed abroad to relieve his symptoms, as he recovered slowly. Conclusion: This case report underscores the importance of a multidisciplinary approach to address SBO. Collaboration between specialists in infectious diseases, otolaryngology, radiology, and neurology plays a pivotal role in achieving an accurate diagnosis and developing a tailored treatment plan. Although SBO may be infrequent, this case report highlights the need to maintain heightened clinical suspicion in high-risk individuals.
