呈急性轴索性运动感觉神经病样表现的线粒体肌病二例:临床病理和基因突变分析

研究背景线粒体肌病主要表现为慢性四肢近端肌无力伴肌肉酸痛,可合并亚临床周围神经损害,而急性轴索性运动感觉神经病样表现伴乳酸酸中毒极为罕见。本研究对2例急性轴索性运动感觉神经病样表现伴乳酸中毒患者的临床特点进行分析,探索其病理和基因突变特点。方法通过周围神经和肌肉肌电图检查,分析神经损害特点;改良Gomori三色、琥珀酸脱氢酶等肌肉组织酶学染色明确肌肉病变性质;电子显微镜观察肌肉组织超微结构改变;24对重叠引物测序法行线粒体基因全序列测定。结果肌电图提示神经源性和肌源性损害并存,运动神经波幅显著降低、传导速度正常,感觉神经波幅轻至中度降低、传导速度正常。病理检查呈慢性肌肉病改变,改良Gomori三色染色可见较多破碎红纤维;电子显微镜观察线粒体数目和形态显著异常,并可见典型的"结晶"样包涵体。线粒体基因全序列测定明确为3243AG(例1)和8344AG(例2)位点突变,均为已知致病突变。结论线粒体肌病可以表现为急性轴索性运动感觉神经病样表现和代谢危象,为急症型,值得重视。     

有机磷中毒后迟发性周围神经病的临床和神经病理四例

目的探讨有机磷中毒后迟发性周围神经病(OPIDP)的临床及神经病理改变特点。方法对4例口服有机磷后出现周围神经损害症状的患者进行电生理和腓肠神经活检检查。结果 4例患者于急性中毒后平均20.5(10～24)天出现以下肢受累为主的逆行性运动感觉周围神经病,其中2例患者存在锥体束征。电生理检查提示以运动神经受累为主的轴索性周围神经损害。腓肠神经活检主要表现为与病程相关的轴索损害及再生现象,可见急性期的炎性反应、小纤维损害和继发的髓鞘改变。结论有机磷中毒后迟发性周围神经病表现为以运动障碍为主的逆行性神经病,中枢神经系统亦可能受累及;周围神经病理表现为轴索损害为主,同时存在小纤维损害及继发的髓鞘改变。     

慢性酒精中毒性肌病的临床与神经电生理学研究

目的　探讨慢性酒精中毒性肌病的临床和电生理改变特点。方法　对 2 6例慢性酒精中毒性肌病、13例慢性酒精中毒性周围神经病、2 1例慢性酒精中毒性神经和肌肉混合损害患者 ,以及 2 0例正常受试者进行详细询问病史、查体 ,并记录酒精摄入量和测定相关神经电生理指标 ,包括肌电图、单纤维肌电图、肌纤维传导速度、周围神经传导速度和诱发电位。结果　 (1)酒精中毒性肌病的主要临床表现为肢带肌的无力、肌肉疼痛和萎缩 ,肌病的症状和体征往往先于周围神经的损害。 (2 )与正常对照受试者比较 ,各组患者神经肌肉颤抖值均增大 (t检验 ,P<0 .0 5 ) ,纤维密度增加 (t检验 ,P<0 .0 5 ) ,周围神经病组患者的神经肌肉颤抖值和纤维密度改变尤为显著 (t检验 ,P<0 .0 1)。 (3)肌病组患者肌纤维传导速度明显减慢 (t检验 ,P<0 .0 5 ) ,其余两组患者无显著变化 (t检验 ,P>0 .0 5 )。结论　 (1)酒精中毒性肌病临床主要表现为对称性肢带肌萎缩、肌力减退和肌肉疼痛。 (2 )肌电图提示肌源性改变 ,特别是肌纤维传导速度减慢 ,是诊断酒精中毒性肌肉病变的客观指征。     

散发性眼咽远端型肌病的临床、肌肉影像与电生理特点

目的探讨眼咽远端型肌病(oculopharyngodistal myopathy,OPDM)的临床、电生理及肌肉核磁影像特点及病理、分子遗传学特点。方法报告1例临床诊断OPDM的临床特点、肌电图、肌肉核磁及病理分析结果、分子遗传学资料,对受累肌肉分布情况及肌电图改变,结合文献进行比较分析。结果患者25岁发病,肌肉受累顺序先后为:眼肌、咽喉肌、肢体远端、双下肢近端,肌酸激酶轻度升高。心脏超声:左室增大,二尖瓣轻度反流,左室舒张功能下降。肌电图显示:脱髓鞘性周围神经病,肌源性损害,为混合性损害。肌肉病理显示:肌源性损害伴镶边空泡肌纤维、可疑线粒体代谢异常。肌肉核磁:小腿脂肪化明显重于大腿,小腿以后群肌受累为主。二代测序未发现已知的远端性肌病、肌营养不良、肌原纤维肌病、空泡性肌病基因突变。结论该患者为散发病例,OPDM作为一类独立表型的肌病,以肌肉受累为主,可以出现脱髓鞘性周围神经损害、心脏受累等多系统表现。     

肌电图肌源性损害合并神经源性损害71例临床分析

目的分析和探讨肌电图(EMG)肌源性损害合并神经源性损害的临床和电生理特点。方法检索作者医院EMG数据库,收集EMG表现为肌源性损害合并神经源性损害患者共71例,对其临床和电生理特点进行回顾性分析。结果在此组患者中,最常见的是结缔组织病,共63例(占88.7%)。其余依次为:肿瘤、进行性肌营养不良、AIDS、甲状腺功能亢进(甲亢)。在全部患者中,临床表现为近端无力者55例(占77.5%),有感觉症状体征者27例(占38.0%),肌肉萎缩者12例(占16.9%)。患者的三角肌52例(占73.2%)、股四头肌49例(占69.0%)EMG表现为肌源性损害,其中上下肢同时为肌源性损害者32例(占45.1%)。所合并存在的神经源性损害主要表现为多发性周围神经病(39例)、单神经病(27例)、颈或腰骶神经根病(5例)。结论EMG检查有助于检出临床下神经肌肉病变,电生理检查发现肌源性合并神经源性损害的同时分析肌病所合并周围神经病变类型将有助于揭示病变性质。     

脂肪累积肌肉病的病理和肌电图改变之间的关系

目的探讨脂肪累积性肌肉病和线粒体脂肪累积性肌肉病的肌肉活检病理改变和肌电图改变之间的关系。方法对33例肌活检确诊患者的肌肉病理改变分为单纯脂肪累积性肌肉病和线粒体-脂肪累积性肌肉病两组,对比两者肌纤维内脂肪沉积的程度以及肌电图改变的差异。结果33.3%为线粒体-脂肪累积性肌肉病,66.7%为单纯脂肪累积性肌肉病。前者肌纤维内脂肪沉积程度显著,7例出现小组样分布的小角状萎缩的肌纤维,后者脂肪沉积的程度相对轻,只有3例患者出现小角状萎缩的肌纤维。在前者81.8%的患者肌电图为肌源性损害、18.2%为混合性损害、45.5%合并周围神经损害。在后者59.1%的患者出现肌源性损害、13.6%出现混合或神经源损害、27.3%肌电图正常、22.7%合并周围神经损害。结论和单纯脂肪累积性肌肉病比较,线粒体-脂肪累积性肌肉病的脂肪滴沉积程度更显著以及更多的患者出现肌纤维萎缩,更易导致骨骼肌的电生理改变以及合并周围神经损害。     

线粒体肌病合并周围神经病的临床病理研究

目的:分析线粒体肌病合并周围神经病的临床特点、电生理和病理特征。方法:对10例肌肉活检确诊为线粒体肌病同时又合并周围神经病的患者从临床症状与体征、电生理检查和腓肠神经活检等几方面予以分析,并探讨周围神经病的病理基础。结果:本组10例患者中1例仅有临床下受累,另外9例表现为轻中度感觉运动性周围神经病,以感觉症状为重。结论:对线粒体肌病患者应将详细的神经系统查体与神经电生理检查相结合,提高周围神经病的检出率。电生理检查和腓肠神经活检有助于诊断。周围神经病的发病机制可能与线粒体功能异常有关。     

MELAS综合征的临床、影像学及病理研究

目的探讨线粒体脑肌病中MELAS综合征患者的临床表现、影像学、组织病理学特点及诊断方法。方法对5例MELAS综合征患者的临床、影像学及神经电生理、肌肉和脑组织病理学特点进行系统分析,3例行肌活检,其中1例患者行肌肉电镜检查;2例行脑活检。结果 MELAS综合征患者主要临床表现为运动不耐受、脑卒中发作、抽搐发作、偏盲、偏头痛发作、听力下降、视力下降。5例患者中血乳酸增高4例,肌电图提示肌源性损害4例,脑电图检查提示重度异常脑电图5例,头颅MRI检查主要为颞、枕、顶叶的不对称病灶;3例患者肌肉组织有破碎红纤维,1例行肌肉电镜检查发现异常线粒体,2例患者脑组织活检可见皮质组织成分层样改变。结论根据患者的临床及影像学特点,并结合肌肉及脑组织活检可对线粒体脑肌病MELAS综合征进行诊断。     

新生儿型神经轴索营养不良的皮肤神经和肌肉病理改变

目的　报道2例新生儿型神经轴索营养不良(INAD)的神经末梢和骨骼肌的病理改变特点。方法　2例患者均为男性,年龄分别为3岁及2岁,均于1岁左右出现智力和运动发育落后或倒退,头颅磁共振成像(MRI)均示小脑萎缩。肌电图提示骨骼肌神经源性损害。例1进行左侧腓肠神经、肌肉和皮肤活检,例2进行左小腿皮肤和肌肉活检,标本进行光镜和电镜检查。结果　2例患者皮下神经末梢均可见椭圆体状巨大轴索,其内充满空泡或致密物质。例1腓肠神经偶见小的致密轴索。例2的骨骼肌间小神经发现异常巨大轴索。两例骨骼肌均存在神经源性病理改变。电镜发现巨大轴索内存在颗粒样物质或空泡膜管样结构。结论　出现中枢神经系统、周围神经系统以及视神经的广泛受累提示INAD的可能性,而脑外病理检查发现神经末梢出现椭圆体样巨大轴索可以确诊该病。巨大轴索内的成分具有不同的超微结构特点。显著的皮肤神经末梢损害提示此病存在小纤维性周围神经病。     

脂质沉积性肌病的临床、神经电生理和病理学特征

目的研究脂质沉积性肌病(LSM)的临床、神经电生理及病理学特点。方法回顾性分析5例LSM患者的临床、神经电生理及病理学资料。结果本组发病年龄平均为25.6岁;均为亚急性或慢性起病,病情缓慢进展或出现缓解复发;2例有家族史;主要表现为运动耐受差和不同程度的肌无力(5/5)、腱反射减弱或消失(5/5)、肌痛或肌压痛(4/5)、肌萎缩(3/5)、末梢型感觉障碍(2/5);肌酶轻至中度升高(4/5),肌电图表现周围神经源性损害合并肌源性损害(2/5),或者单纯肌源性损害(1/5);肌肉病理学显示纤维间、肌膜下、胞核周围大量排列成串的或成团的脂滴,无炎性细胞浸润。高肉碱、低脂肪饮食、以及糖皮质激素治疗有效。结论LSM临床以肌无力和运动不耐受为主要症状,神经电生理表现为肌源性损害和/或周围神经损害,肌肉活检为诊断脂质沉积性肌病所必需。     

Colchicine-induced myopathy with myotonia in a patient with chronic renal failure

Although colchicine induced myopathy has been described in patients with chronic renal failure, colchicine induced myopathy with myotonia has been reported very rarely. A 49-year-old man with chronic renal failure was hospitalised for investigation of fatigue, malaise and severe pain in all extremities. He was on colchicine therapy for 5 months. Neurological examination showed mildly decreased sensation in a distal symmetric pattern in lower extremities, moderate proximal limb weakness, hyporeflexia and severe myalgia on palpation. No clinical evidence of myotonia was present. Laboratory studies showed elevated creatine phosphokinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Electromyographic (EMG) findings were compatible with myopathy and abundant, widespread myotonic discharges were determined. Muscle biopsy was consistent with vacuolar myopathy. After withdrawal of colchicine, CK, LDH, AST and ALT levels were normalised and the symptoms were disappeared gradually. In conclusion, the detection of myopathic motor unit potentials with myotonic discharges on EMG in patients on colchicine therapy is an important finding and it is possible to suggest that this clue may lead to the invasive procedure of muscle biopsy unnecessary.     

Mitochondrial myopathy and myoclonic epilepsy

The authors describe a family (mother, son and two daughters) with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.     

Skeletal muscle toxoplasmosis in patients with acquired immunodeficiency syndrome: a clinical and pathological study.

The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.     

替比夫定与聚乙二醇干扰素α-2a联用导致感觉神经病二例

目的 报道2例使用替比夫定和聚乙二醇干扰素α-2a联合治疗乙型肝炎导致的感觉神经病患者,对其临床、电生理和病理改变规律进行讨论.方法 2例男性患者分别为48岁和20岁,均为慢性乙型肝炎病毒感染者,在应用替比夫定和聚乙二醇干扰素α-2a治疗4个月后出现双下肢麻木和疼痛,症状进行性加重.体检发现均出现四肢远端痛觉减退,例2出现腱反射减低.2例均出现四肢远端无汗,例1出现手指和足趾的甲根部灰白样改变.例2伴随出现下肢轻度肌力下降和血清肌酸激酶轻度升高.对2例患者进行电生理检查及腓肠神经病理检查.结果 2例患者的电生理检查发现感觉神经动作电位波幅显著减低,传导速度轻度下降,其中1例出现运动神经动作电位波幅减低.腓肠神经活体组织检查显示有髓神经纤维中度减少、有髓神经纤维轴索变性和轻度再生簇形成.电镜检查进一步发现无髓神经纤维也出现减少.停止药物治疗并给予B族维生素、辅酶Q10和左旋肉碱治疗后症状好转.结论 替比夫定联合聚乙二醇干扰素α-2a治疗可以导致感觉神经病,出现轴索性神经病的电生理和病理改变特点.此病具有可逆性.     

Reappraisal of alcoholic myopathy: Clinical and biopsy study on chronic alcoholics without muscle weakness or wasting

To determine if alcoholic neuropathy which causes denervation of the distal muscles of chronic alcoholics also produces a subclinical myopathy of their proximal muscles, we studied 11 chronic alcoholics who had no muscular weakness or wasting. Six patients demonstrated distal hyporeflexic (ankle jerks) sensory neuropathy on clinical examination. Four patients, one of whom was asymptomatic, had slow peroneal motor nerve conduction velocities. Patterns of neuropathy were present in the electromyograms of the proximal muscles of two patients. Muscle biopsy studies with enzyme histochemistry indicated denervation atrophy and myopathic changes in the contralateral quadriceps muscles of eight patients. As denervation atrophy was present, we concluded that these myopathic changes represented the effects of denervation of these muscles. We conclude, therefore, that the proximal subclinical alcoholic myopathy, previously described as primary by ourselves and others, is the result of denervation due to the well-known alcoholic neuropathy.     

Benign reversible muscle cytochrome c oxidase deficiency: a second case

A 6-week-old boy had generalized weakness, requiring assisted ventilation, and lactic acidosis. At 6 months, the lactic acidosis resolved, and the patient started to improve; assisted ventilation was discontinued at 15 months. Muscle biopsies at 4 and 11 months showed accumulation of mitochondria, lipid, and glycogen; cytochrome c oxidase (COX) activity was 11% of the lowest control in the first biopsy and 57% in the second. Immunocytochemistry and immunotitration showed presence of immunologically reactive enzyme protein in both biopsies. This case confirms a previous report of benign infantile myopathy due to reversible COX deficiency. The severe fibrosis in the second biopsy may explain the slower rate of clinical recovery in this child.     

Myopathy with antibodies to the signal recognition particle: clinical and pathological features

OBJECTIVES: To study myopathies with serum antibodies to the signal recognition particle (SRP), an unusual, myositis specific antibody associated syndrome that has not been well characterised pathologically. METHODS: Clinical, laboratory, and myopathological features were evaluated in seven consecutive patients with a myopathy and serum anti-SRP antibodies, identified over three years. The anti-SRP myopathy was compared with myopathology in other types of inflammatory and immune myopathies. RESULTS: The patients with anti-SRP antibodies developed weakness at ages ranging from 32 to 70 years. Onset was seasonal (August to January). Weakness became severe and disability developed rapidly over a period of months. Muscle pain and fatigue were present in some patients. No patient had a dermatomyositis-like rash. Serum creatine kinase was very high (3000 to 25 000 IU/l). Muscle biopsies showed an active myopathy, including muscle fibre necrosis and regeneration. There was prominent endomysial fibrosis, but little or no inflammation. Endomysial capillaries were enlarged, reduced in number, and associated with deposits of the terminal components of complement (C5b-9, membrane attack complex). Strength improved in several patients after corticosteroid treatment. CONCLUSIONS: Myopathies associated with anti-SRP antibodies may produce severe and rapidly progressive weakness and disability. Muscle biopsies show active myopathy with pathological changes in endomysial capillaries but little inflammation. Corticosteroid treatment early in the course of the illness is often followed by improvement in strength. In patients with rapidly progressive myopathies and a high serum creatine kinase but little inflammation on muscle biopsy, measurement of anti-SRP antibodies and pathological examination of muscle, including evaluation of endomysial capillaries, may provide useful information on diagnosis and treatment.     

AZT myopathy and HIV-1 polymyositis: one disease or two?

PURPOSE: This paper discusses the association between inflammatory and mitochondrial pathologies in patients with HIV-1/AIDS treated with zidovudine (AZT). METHODS: We present the clinical and pathological details of a 52-year-old HIV-1 positive male who presented with progressive muscle weakness. We also review the current literature and address the debated pathogenesis of the inflammatory pathology. RESULTS: Muscle biopsy revealed evidence of both HIV-1 polymyositis and AZT myopathy. Six months after initiation of corticosteroid therapy and discontinuation of AZT, the patient's symptoms had greatly improved. The biopsy was repeated to show that both pathologies had resolved. CONCLUSIONS: The perceived overlap in the pathological spectra of HIV-1 polymyositis and AZT myopathy has produced some debate on causation and treatment. Unfortunately, there have been very few reports where a repeat biopsy following a drug washout period confirmed resolution of the pathology. Furthermore, affected patients have not been treated in a uniform fashion. Whether this represents one disease or two remains uncertain. The clinical relevance of this issue lies in the potential for harm from the unnecessary use of corticosteroids. This question may be best addressed by a randomized clinical trial.