Objective:To summarize the clinical, imaging, muscle pathological and gene mutational features of patients with late-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).Methods:Three patients with late-onset MELAS, admitted to Department of Neurology, Jiaozuo People's Hospital Affiliated of Xinxiang Medical University from January 1997 to December 2021 were chosen; all patients were screened for mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) mutations by second-generation gene sequencing. The clinical, imaging, muscle pathological and gene mutational features of patients with late-onset MELAS were analyzed retrospectively.Results:The main clinical manifestations of these late-onset MELAS patients included stroke-like attacks, headache, hearing and vision loss, cognitive decline and mental disorder. The muscle tension and muscle strength of both upper extremities in these 3 patients were normal. Increased muscle tension and active tendon reflexes, and positive pathological signs in both lower extremities were noted in 2 patients. Head MRI showed abnormal long T1 and long T2 signals in temporal occipital parietal cortex and subcortex in 3 patients, and CT showed calcification in bilateral globus pallidus in 1 patient. Ragged red fibers (RRF) and ragged blue fibers (RBF) were found in the muscle biopsies of 3 patients, and cytochrome oxidase (COX)-negative muscle fibers were found in 2 patients. MT-TL1 gene m.3243A>G mutation was detected in all 3 patients by genetic testing, among which mutation in the blood of 2 patients was 15% and 17%, respectively, and mutation in the muscle tissues of 1 patient was 73%. Conclusion:Muscle pathology indicates high RRF percentage in patients with late-onset MELAS; and m.3243A>G spot mutation is the most common mutation type in late-onset MELAS, and m.3243A>G mutation ratio in muscle tissues is obviously higher than that in blood.

Objective:To summarize the characteristics of clinical, muscle pathology and gene mutation of late-onset reducing body myopathy caused by FHL1 gene mutation, in order to improve clinicians′ understanding of this disorder. Methods:The clinical, muscle pathology and muscle magnetic resonance imaging data of the proband from a family diagnosed as reducing body myopathy in Jiaozuo People′s Hospital in December 2021 were collected. Genetic tests and pedigree verification were conducted on the proband and her son.Results:The proband was a 59-year-old female with progressive, asymmetrical limb weakness and muscular atrophy. Her mother, sister and brother had similar symptoms. Electromyography showed myogenic and neurogenic damage. Muscle magnetic resonance imaging indicated that the lesion mainly involved the posterior muscles of the thigh and calf, as well as the gluteus maximus. The muscle pathology showed eosinophilic granular inclusion bodies and rimmed vacuoles in the muscle fibers of the lesion. The structure of myofibrils was disordered and abnormal protein deposition was observed. The gene sequencing showed the FHL1 gene p.C150S heterozygous variation. Conclusions:Late-onset reducing body myopathy is characterized by progressive asymmetric proximal limb muscle weakness, partially involving distal limb muscles and gluteus maximus. Muscle pathology shows the characteristic pathological changes of many kinds of myofibrillar myopathies. FHL1 gene mutation is an important basis for diagnosis.

女，36岁，3年前无诱因出现双手无力，表现为手指屈曲力弱、握拳不紧(图1A、1B)，症状缓慢进展。1年前出现走路姿势异常，腰部前倾。1月前发现双足踇不能上翘，双手肌肉轻度萎缩。家族中无类似患者。查体：颅神经功能正常，转头、耸肩力弱，屈颈2级，伸颈4级。四肢肌张力正常，肌力检查臂外展、伸、屈肘均为5级，伸、屈腕4级，伸指4-级，屈指4-/3级(左/右)，伸、屈髋5级，伸、屈膝5-级，跖屈4级，背伸4-级，踇背伸2级，双手大鱼际肌萎缩(图1C)，双上肢腱反射+，双下肢腱反射++，双侧病理征均为阴性。起蹲正常，无法用足跟行走。内科系统查体未见异常。

Objective:To investigate the clinical characteristics and electron transfer flavoprotein dehydrogenase ( ETFDH) genetic mutations in patients with riboflavin responsive lipid storage myopathy (RR-LSM). Methods:A retrospective analysis was performed. The clinical data and muscular pathology of 26 patients with RR-LSM, admitted to our hospital from January 2009 to June 2021, were collected. Peripheral venous blood DNA was extracted, and the mutations of ETFDH gene were detected and analyzed by whole exome sequencing. Results:These 26 patients had onset of proximal limb myasthenia, 17 patients had difficulty in raising their head, 12 patients had mastication weakness, 6 had dysphagia, 5 had nausea and vomiting, and one was complicated with rhabdomyolysis and one was with reversible splenic lesion syndrome. Muscle biopsy indicated pathological deposition of lipid droplet, which type I fibers were involved mainly; degenerative necrotic muscle fibers were seen in a few cases. ETFDH gene mutations were detected in 26 patients; 23 patients had compound heterozygous mutation, two had single heterozygous mutation and one had homozygous mutation; 25 different mutation sites were found, mainly missense mutations; the C.770A>G frequency was the highest, accounting for 20% alleles (10/50); two novel mutation sites were found: c.1115A>G and c.1781T>C. Conclusion:RR-LSM is mainly characterized by proximal limb muscle weakness and fatigue intolerance, often accompanied by neck extensor and masticatory weakness; c. 770A>G is the hot site of ETFDH genetic mutations in RR-LSM patients.

Objective:To investigate the characteristics of clinical, muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods:The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020. The next generation sequencing was preformed to detect NEB gene in all patients, and characteristics of gene mutation were analyzed.Results:Among the 11 patients, there were 8 males and 3 females, and 6 of them came from 2 families. The age of seeing a doctor ranged from 11 to 52 years, the age of onset was from 6 to 23 years, and the course of disease ranged from 5 to 35 years. Neurological examination showed that among the 11 patients, 8 patients had high palatal arch and long face. The muscle tone of both upperlimbs was normal, the tendon reflex was depressed, the proximal muscle strength was grade Ⅲ-Ⅴ, and the distal muscle strength was grade Ⅴ. The muscle tone of both lower extremities was reduced and the tendon reflex was absent. The proximal muscle strength was grade Ⅱ-Ⅳ and the distal muscle strength was grade Ⅲ-Ⅴ. No dysphagia or respiratory muscle involvement was found. Muscle biopsies were performed in 7 of the 11 patients, the pathological changes were muscle fibers of different sizes, circular atrophic muscle fibers and compensatory hypertrophic fibers, and occasionally denatured and necrotic muscle fibers were found. Different degrees of rod aggregation could be seen in all the 7 patients. Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils, and most of them were located near the Z band, but no intranuclear rod was found. NEB gene was found in all 11 patients, and a total of 9 different mutation sites were detected, including 8 in exon region and 1 in intron region. Among them, c.21522+3A>G was found in 10 cases, c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases. There was 1 case of c.4417C>T, c.2549delA, c.21065dupA, c.3520G>A, c.20943G>A, c.192G>A respectively.Conclusions:The clinical phenotype of nemaline myopathy caused by NEB gene has great heterogeneity. Muscle pathology shows that rod aggregation is an important basis for the diagnosis of this disease. Mutation c.21522+3A>G in intron is the most common mutation in this group of NEB gene. And the novel mutation sites of NEB gene are respectively c.17611C>T, c.2549delA, c.3520G>A, c.21065dupA, c.20943G>A and c.192G>A.

目的 探讨ETFDH基因突变致核黄素反应性脂质沉积性肌病(Riboflavin-responsive lipid storage myopathy,RR-LSM)的临床、病理和ETFDH基因突变特点.方法 回顾性分析2009年1月-2020年12月就诊于我院,经肌肉活检病理确诊和基因检测证实的18例RR-LSM患者的临床和病理资料,并采取外周血DNA进行Illu-mina NovaSeq高通量测序,进行数据读取和生物信息学分析.结果 18例患者中男女各9例,发病年龄9～60岁,平均(29.83±13.44)岁,病程1 m～22 y,平均4.5 y.主要临床表现为肢体近端无力和运动不能耐受,伴颈伸肌无力14例,咀嚼肌无力9例,吞咽困难5例,恶心纳差5例,少数患者伴有肌肉疼痛和呼吸困难.本组患者肌肉病理均可见肌纤维内有大量脂质沉积,5例可见少量坏死肌纤维,伴有CD68(+)的巨噬细胞浸润.18例患者经核黄素治疗均获得良好疗效.本组病例均检测到ETFDH基因突变,其中复合杂合突变15例(83.3％),单一杂合突变2例(11.1％),纯合突变1例(5.6％).共发现20个突变位点,其中频率最高的突变位点为c.770A>G,占等位基因的19.4％(7/36),其次为c.1454C>G,占等位基因的8.3％(3/36).结论 ETFDH基因突变所致的RR-LSM患者以躯干中轴肌和咀嚼肌受累为特点,肌肉病理发现肌纤维内有大量脂质沉积是诊断的重要依据.c.770A>G和c.1454C>G是本组病例ETFDH基因最常见的突变位点.

肉芽肿性肌炎(GrM)是一组发生在横纹肌的非特异性上皮样肉芽肿性炎性反应综合征,临床上多表现为肌痛、肌无力、皮下结节和吞咽困难,可有肌酶不同水平的升高、炎性肌病的神经电生理表现.病理检查是确诊的主要手段,典型的肌肉病理可发现多核巨细胞和肌纤维炎性改变.肉芽肿性肌炎最常与结节病和结缔组织疾病伴发[1],少有同时合并重症肌无力的病例报道.我们在临床中发现了1例罕见的重症肌无力合并肉芽肿性肌炎的患者,从诊断和治疗过程中吸取了一定的经验教训,现对该病例和文献报道的7例类似病例进行分析,初步概括其特点,为临床同道提供借鉴.

1 病例介绍 患者女性,66岁,主因"头晕、意识障碍15?min"于2020年9月2日09:43急诊入院.患者于15?m i n前行走中突发头晕,随即出现意识不清、摔倒在地,无恶心、呕吐、肢体抽搐及大小便失禁,家属打120送至我院.

目的 探讨伴骨骼肌损害的嗜酸性肌筋膜炎的临床特点及病理改变.方法 对5例伴骨骼肌损害的嗜酸性肌筋膜炎的临床特征及组织病理学进行回顾性分析,采用免疫组化EnVision法检测淋巴细胞CD4、CD8、CD20和CD68的表达,并复习相关文献.结果 5例患者临床主要表现为不同程度的肢体肿胀,肌肉疼痛无力,均以肢体远端为主.其中4例患者局部皮肤有色素沉着和橘皮样改变,3例出现双手握拳困难,呈"空心拳"征.肌电图检查肌源性损害4例,血清肌酸激酶升高3例.5例患者骨骼肌和筋膜组织病理活检:均可见不同程度的肌筋膜增厚和小血管增多,并伴有炎性细胞浸润.在与深筋膜相邻的骨骼肌组织中可见部分肌纤维变性坏死,伴炎性细胞浸润.免疫组化提示炎性细胞主要为CD8+和CD68+淋巴细胞浸润.结论 嗜酸性肌筋膜炎可累及相邻的骨骼肌组织引起肢体远端无力,肌肉和筋膜组织活检是确诊的重要手段.

目的 探讨杆状体肌病的临床特点、肌肉MRI改变和基因突变.方法 回顾性分析1例NEB基因新复合杂合突变致儿童型杆状体肌病患者的临床资料.结果 本例患者为男性,6岁发病,以双下肢远端无力起病,逐渐向近端发展,14岁行肌肉活检在肌纤维内发现大量杆状体而被确诊,29岁复诊时做基因检测明确为NEB基因突变.双下肢肌肉MRI提示双侧股外侧肌、股中间肌、大收肌萎缩并脂肪变性.双侧比目鱼肌脂肪变性并萎缩,腓肠肌内侧头和胫前肌水肿.与文献报道不同的是本例患者双下肢远端无力明显重于近端,且发病23年仍未累及颈肌和上肢肌肉.基因检测发现NEB基因有两处杂合突变,c.2549delA发生移码变异,c.21522+3A>G发生点突变,家系验证结果显示这两处杂合突变分别来自其父亲和母亲.目前文献报道NEB基因已发现有312种突变,本例发生在第27号外显子上的c.2549delA突变,在人类基因数据库和HGMDpro数据库中亦均未见有报道,为新发现的突变位点.结论 杆状体肌病临床表型异质性较大,肌肉病理和基因检测是诊断的重要依据,c.2549delA为NEB基因新发的突变位点.

线粒体神经胃肠型脑肌病(mitochondrial neurogastroint-estinal encephalomyopathy,MNGIE)是一种罕见的常染色体隐性遗传的多系统疾病,由于核基因TYMP突变导致胸苷磷酸化酶(thymidine phosphorylase,TP)缺陷所致[1].TP的活性降低或缺失,可导致脱氧胸苷和脱氧尿嘧啶核苷在组织中的蓄积,引起线粒体功能的异常,从而导致患者出现多系统受累的临床症状.MNGIE典型的临床症状包括严重的胃肠动力障碍、脑白质病变、眼外肌麻痹、周围神经病变和肌肉萎缩[2].自2012年许二赫等首次在国内报道了该病以来[3],目前国内约有13例MNGIE的相关报道[4-8].本文报告1例经肌肉病理与基因检测共同确诊的MNGIE患者,与以往文献报道不同的是本例患者的脑影像不仅有脑白质病变,而且有双侧基底节区和小脑齿状核病变.基因检测发现TYMP基因在7号和10号外显子区域分别有c.914T＞C和c.1319T＞C两处新发的错义突变,扩展了TYMP基因的变异谱系.

Objective: To investigate the clinical features, skeletal muscle imaging, and muscle pathological characteristics of late-onset GSD IIIa caused by mutation of the AGL gene in adults. Methods: The clinical data, skeletal muscle imaging, pathological data, and gene test results of a family with late-onset GSD IIIa in adulthood were collected in detail in November 2019. Results: The proband is a 40-years-old male, who was admitted into our hospital due to a 2-years history of limb weakness. The proband was diagnosed with the following syndrome: he had a 15-years history of elevated muscle enzymes; the cranial nerve examinations showed no abnormal findings; the muscle tension in both upper and lower limbs was low, and tendon reflexes were absent; the proband's muscle strength was 5 in the proximal muscles and 4 in the distal muscles of the upper limbs, with 3 in the proximal muscles and 4 in the distal muscles of the lower limbs; Magnetic Resonance Imaging (MRI) revealed abnormally high signal intensity changes in the posterior thigh muscle group, and the posterior-medial calf muscle group; and vacuoles were evident in some muscle fibers biopsied from the gastrocnemius muscle. Periodic acid-Schiff staining stained the cytoplasm of muscle fibers a dark red color. The proband's older brother exhibited the same clinical features. DNA analysis identified mutations in the AGL gene in the proband, his older brother, and parents. The proband and his older brother both carried two compound heterozygous mutations, c.866G>A and c.2855_2856insT. Pedigree analysis demonstrated that c.866G>A and c.2855_2856insT mutations had been inherited from the mother and father, respectively. Conclusion: Late-onset GSD IIIa in adults is clinically characterized by muscle weakness, muscle atrophy, and mainly occurred in the posterior thigh muscle group. We also identified two novel compound heterozygous mutations (c.866G> A and c.2855_2856insT) in the AGL gene.

The aim of the present study was to explore the clinical, neuroelectrophysiological and muscular pathological characteristics of chronic progressive external ophthalmoplegia (CPEO) and to improve the understanding of CPEO. Clinical manifestations, neuroelectrophysiology and pathological features of muscle biopsies from 12 patients with CPEO were retrospectively analyzed. The average age of onset for the 12 patients (6 males and 6 females) was 17.2 years. All patients had different degrees of blepharoptosis. A total of 11 patients experienced ocular dyskinesia, but diplopia was rare. Electrophysiological testing in 12 patients revealed abnormal changes in 6 patients, including 4 patients with a myogenic lesion, 1 patient with a neurogenic lesion, and 1 patient with mixed myogenic/neurogenic lesions. Two patients had slow sensory nerve conduction velocity. Muscle biopsies in 12 patients demonstrated ragged-red, irregular and broken fibers in 11 patients through Gomori trichrome and hematoxylin and eosin (H&E) staining, increased lipid levels in some muscle fibers in 4 patients through omicron il ed O staining and abnormal distribution of type I and II muscle fibers in 3 patients through ATPase staining. Electron microscopy in 5 patients showed an increased number of mitochondria and abnormal mitochondrial aggregation between submucosa and myofibrils in 4 patients. These findings suggest that the possibility of CPEO should be considered if patients present with obvious extraocular muscle paralysis without diplopia. Furthermore, the identification of ragged-red fibers by Gomori trichrome and H&E staining of muscle biopsies from patients is an important basis for the diagnosis of CPEO.

亨廷顿病(Huntington disease,HD)又称亨廷顿舞蹈病,是一种常染色体显性遗传性神经变性疾病,主要临床表现为慢性进行性舞蹈样不自主运动、精神障碍和痴呆.IT15基因为HD的致病性基因,IT15基因1号外显子内含有一段多态性三核苷酸( CAG)重复序列,当患者CAG重复拷贝数大于35次时即可引起发病[1].我们收集1例IT15基因变异导致的亨廷顿舞蹈病家系,三代人中共有4例发病,本文对其临床特点、脑影像学改变和基因检测结果进行分析总结,并结合相关文献进行讨论.

多酰基辅酶A脱氢缺陷(multiple acyl coenzyme A dehydrogenation deficiency,MADD)是一种影响脂肪酸、氨基酸及胆碱代谢的常染色体隐性遗传病,主要由电子转运黄素蛋白(ETF)或电子转运黄素蛋白脱氢酶(ETFDH)的基因突变所致.MADD主要临床表现为波动性肌无力和运动不能耐受,以肢体近端肌和颈伸肌无力为特征.由于MADD临床表型的异质性,使其早期很容易被误诊为多发性肌炎、重症肌无力、线粒体肌病等.肌肉活检和血尿生化检测有助于MADD的早期诊断,对阴性患者可进行MADD相关的基因检测.核黄素是目前MADD最有效的治疗药物.

目的 探讨伴有肌纤维坏死的脂质沉积性肌病患者的骨骼肌病理改变及其临床特点.方法 回顾性分析8例伴有肌纤维坏死的脂质沉积性肌病患者的肌肉组织病理改变和临床特点.结果 8例患者中上肢近端肌力3级以下者4例(其中2例伴呼吸肌受累),下肢近端肌力3级以下者6例;8例均伴有颈伸肌无力;8例患者除肌纤维内大量脂质沉积外,均伴有不同程度肌纤维变性坏死,其中5例偶见变性坏死肌纤维,坏死肌纤维比率0.1％～0.9％,病程较长且年龄偏大,有反复出现肌无力的病史;3例可见较多变性坏死纤维,坏死肌纤维比率＞1.0％,病程较短、进展迅速且较年轻,其中2例免疫组织化学结果显示CD4(一)、CD8(一)、CD20(--)、CD68(+);3例基因检测显示ETFDH基因突变.结论 部分脂质沉积性肌病患者的肌肉病理中可见变性坏死肌纤维,伴有明显肌纤维坏死者临床症状较重,病情进展较快.

目的 观察静脉溶栓桥接机械取栓在脑梗死患者中的治疗效果.方法 取2014-12—2016-10焦作市人民医院神经内科二区收治脑梗死患者60例,采用随机数字方法将患者分为对照组(n=30)和观察组(n=30).对照组采用静脉溶栓治疗,观察组在对照组基础上联合机械取栓治疗,比较2组临床疗效.结果 2组治疗前NIHSS、FIM评分比较差异无统计学意义(P>0.05);观察组治疗后NIHSS评分低于对照组(P<0.05),观察组治疗后FIM评分高于对照组(P<0.05);2组治疗后3个月颅内出血率及病死率比较差异无统计学意义(P>0.05).结论 脑梗死患者在静脉溶栓基础上联合机械取栓治疗效果理想,能提高临床治疗效果,改善患者预后,值得推广应用.

目的:探究阿尔茨海默病患者海马代谢的磁共振波谱的分布规律以及特点,为临床诊断提供重要的参考依据.方法:采用对比实验方法,以20例阿尔茨海默病患者作为实验组患者,选取同期年龄性别等基本相似的20例健康人作为对照组,对两组研究对象的智力状况、认知能力等进行简单的评定,同时采用核磁共振波普成像检查技术和方法对两组研究对象的核磁波谱分布状况和规律进行对比和分析.结果:两组智力状况、认知能力、海马区核磁共振谱的各项指标存在显著差异(P<0.05).结论:阿尔茨海默病患者海马区的图谱明显与健康研究对象有明显的差别,这临床诊断提供了有效的证据,具有重要的价值和意义.

目的 观察Solitaire AB支架取栓术在急性脑梗死患者中的临床治疗效果及对功能恢复的影响.方法 取急性脑梗死患者60例,分为对照组(n=30)和观察组(n=30).对照组采用静脉溶栓治疗,观察组采用Solitaire AB支架取栓术治疗,采用脑卒中量表(NIHSS)评分、mRS评分对患者治疗前、后功能恢复情况进行评估,比较2组临床疗效及对功能恢复的影响.结果 观察组治疗后即刻、治疗后24h NIHSS评分,高于对照组(P<0.05);观察组治疗后3d、3周NIHSS评分,低于对照组(P<0.05);2组患者治疗后症状性颅内出血、死亡率比较差异无统计学意义(P>0.05);观察组mRS≤2分患者,多于对照组(P<0.05).结论 急性脑梗死患者采用Solitaire AB支架取栓术治疗效果理想,能提高患者功能恢复,值得推广应用.

Objective To expore the correlation between plasma homocysteine (Hcy) level and mutation of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in middle-age and young patients with ischemic cerebravascular diseases (ICVDs).Methods Two hundred and twenty patients with ICVDs (≤ 55 years),admitted to our hospital from January 2010 to September 2012,were included as the case group while 203 subjects without stroke and coronary arterial disease matched with the case group for gender and age were collected as the control group.Plasma Hcy level was measured using fluorescence polarization immunoassay; and MTHFR c677T mutant was determined by polymerase chain reaction and restriction fragment length polymorphism.Results The mutated T allele frequencies in case and control groups were 59.8％ and 45.8％ with statistically significant difference (P＜0.05); homozygous mutant TT and heterozygous mutant CT,homozygous wild type CC between the two groups were statistically different (P＜0.05).The level of plasma Hcy were (32.16±19.52) μmol/L in the case group and (18.73±8.75) μmol/L in the control group with statistical significance difference (P＜0.05).The level of plasma Hcy of case and control groups with TT type was significantly higher than that with CT and CC types (P＜0.05).Multivariate Logistic regression analysis showed that age,hypertension,low-density lipoprotein cholesterol,diabetes mellitus,and high Hcy were risk factors for onset of ICVDs in middle-age and young patients.Conclusions High plasma Hcy level is a risk factor for onset of ICVDs in middle-age and young patients; MTHFR gene C677T homozygous mutation can induce an increase in plasma Hcy level,and there may be interactions with other factors.