伴小脑萎缩的线粒体脑肌病MELAS一例

线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)是一种少见的遗传性疾病,可累及机体多系统。该病主要临床表现为头痛、癫痫、耳聋、皮质盲及认知功能下降等。MELAS呈卒中样发作,临床易误诊为脑梗死及脑炎,目前尚缺乏特效治疗方法。该文报道1例33岁女性MELAS患者,其以突发头痛、视物不清为首发症状,伴有不完全感觉性失语、听力下降、不能耐受疲劳,急诊颅脑CT显示双侧小脑半球萎缩,入院后经外周血基因检查明确MELAS诊断,予辅酶Q10胶囊、艾地苯醌及维生素E治疗。患者病情好转后出院,随访3个月病情稳定。该病例提示临床医师应提高对MELAS的认识,注意鉴别诊断,避免漏诊或误诊。     

MELAS综合征的影像学特点

目的：探讨MELAS综合征影像学特点及诊断价值。方法：回顾性分析6例MELAS综合征的临床、影像学及肌肉病理资料。结果：3例颅脑CT未发现钙化。10次卒中样发作颅脑MRI发作期常规T1、T2加权相表现为颞顶枕叶皮质及皮质下白质长T1、T2异常信号，2例弥散加权成像表现为相应部位脑回样高信号。恢复期受累部位表现为局限性萎缩，可显示典型层状坏死。5例患者肌肉Gomori染色可见典型的破碎红边纤维。结论：MRI反复颞顶枕叶皮质及皮质下白质病灶可为临床诊断提供帮助，与在脑梗死诊断中的作用类似，弥散加权成像可能会更早地显示病灶。     

一种新的线粒体DNA基因突变:线粒体脑肌病伴高乳酸血症和卒中样发作综合征1例基因与残障特征分析

背景线粒体脑肌病伴高乳酸血症和卒中样发作综合征(MELAS)是线粒体脑肌病中最常见的一种临床类型,多种线粒体基因突变均可导致MELAS.目的探讨1例MELAS患者的临床表现和线粒体基因突变的关系.设计临床、病理和基因分析对照研究.地点和对象实验在解放军济南军区总医院神经内科病房、神经病理实验室和神经分子生物学实验室进行.患者,男,13岁,因发作性头痛、呕吐,肢体抽搐1个月于2001-06-04入院,入院后逐渐出现失明和智能减退.血乳酸和丙酮酸水平升高,临床诊断MELAS.干预对患者行头颅MRI检查、脑活检病理检查和线粒体基因分析.主要观察指标临床表现特点、MRI病变特征、脑组织病理改变特点以及线粒体基因突变类型.结果患者不存在能引起MELAS的较常见的突变,但在线粒体3314～3589之间有276 bp的碱基缺失.结论线粒体DNA 3314～3589位点之间276 bp的碱基缺失可能是能够导致MELAS的一种新的基因突变类型,也是导致患者出现失明、癫痫和痴呆的原因.     

酷似免疫性脑炎的线粒体脑肌病伴乳酸酸中毒及卒中样发作综合征的诊断学特征

目的探讨酷似免疫性脑炎的线粒体脑肌病伴乳酸酸中毒及卒中样发作(MELAS)综合征的临床、神经电生理及影像学改变的诊断学特征,总结诊疗过程。 方法回顾性分析1例酷似免疫性脑炎的MELAS综合征的发病过程及临床资料,并复习相关文献。 结果患儿曾以发热、头痛、恶心、呕吐、视物模糊、眼球阵挛、步态不稳等相似症状分别于3,6个月前误诊为病毒性脑炎、免疫性脑炎两次住院,经治疗症状逐渐好转出院。现以相同症状加重并出现视物不清、行走困难再次入院。检查脑脊液常规及抗N-甲基-D-天冬氨酸受体(NMDA-R)抗体阴性,脑电图显示右侧枕部、后颞部大量散发－阵发性棘波/棘慢复合波、尖波/尖慢复合波,可波及右侧顶部;头颅磁共振(MRI)表现多样,可累及皮质和髓质,以灰质为主,表现为脑回明显肿胀,脑沟变窄、变浅,DWI呈弥散受限高信号,晚期脑组织可出现局部软化、脑萎缩改变,病灶可反复出现,基因检测A3243G位点突变,最终确诊为MELAS综合征。 结论临床症状酷似免疫性脑炎的患儿,遇有病情不稳、症状反复出现,应做进一步检查,排除或确诊是否为MELAS综合征。     

Diagnosis and management of MELAS

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is the most common maternally inherited mitochondrial disease. An A-->G mutation in the transfer RNA(Leu(UUR)) gene at position 3243 of the mitochondrial DNA accounts for most MELAS cases. The transient nature of the stroke-like episodes is reflected in abnormalities on neuroimaging. The cardinal laboratory abnormalities include elevated serum lactate during the acute episodes and respiratory enzyme defects in skeletal muscle. Muscle biopsy also helps confirm the diagnosis by identifying abnormal proliferation of mitochondria. Although current treatment options for MELAS are largely supportive, several therapeutic approaches have been attempted with limited success. Genetic counseling is an important component of patient management in MELAS. Newer reproductive technologies hold promise for reducing the recurrence of MELAS in subsequent generations. Advances in research into gene therapy offer hope of treatment for the future.     

质子磁共振波谱对MELAS诊断的初步评价

目的探讨质子磁共振波谱(1HMRS)在MELAS型线粒体脑肌病中的特点及其诊断价值。方法7例临床诊断为线粒体脑肌病的患者行MRI及1HMRS检查,分析其MRS检查技术、谱线特点、与临床实验室检查的关系。结果7例患者MRI脑内均有异常表现,异常信号主要出现在双侧枕叶、顶叶、颞叶,其中4例合并基底节受累,2例额叶轻度受累,1例合并双侧中脑大脑脚、丘脑受累,1例左侧岛叶受累;1HMRS的谱线显示6例患者病变处可检出乳酸双峰,其中3例在脑脊液中检出乳酸峰。结论在MELAS型线粒体脑肌病中1HMRS可提供额外的直接反映疾病代谢异常的信息,有助于其诊断的确立,且具有替代传统有创检测脑脊液乳酸水平方法的潜能。     

Headache and mitochondrial disorders

We report on 2 patients who have a mitochondrial myopathy, encephalopathy, lactic acidosis, and recurrent cerebral insults that resemble strokes (MELAS). These 2, and 9 other, reported patients share the following features: ragged red fibers evident on muscle biopsy, normal early development, short stature, seizures, and hemiparesis, hemianopia, or cortical blindness. Lactic acidemia is a common finding. We believe that MELAS represents a distinctive syndrome and that it can be differentiated from 2 other clinical disorders that also are associated with mitochondrial myopathy and cerebral disease: Kearns–Sayre syndrome and the myoclonus epilepsy ragged red fiber syndrome. Existing information suggests that MELAS is transmitted by maternal inheritance. The ragged red fibers suggest an abnormality of the electron transport system, but the precise biochemical disorders in these 3 clinical syndromes remain to be elucidated.     

MELAS型线粒体脑肌病的多模态MRI诊断

目的：探讨MELAS型线粒体脑肌病的多模态影像学特点.方法：对11例MELAS型线粒体脑肌病患者的脑MRI、MRA、DWI及MRS影像资料进行分析.结果：MRI：MELAS病灶多位于枕顶叶大脑皮层,多发为主,多变性、游走性,与血管的走行不一致,5例海马、海马旁回受累,5例合并基底节核团受累,4例合并大脑和（或）小脑萎缩,7例增强扫描未见强化;MRA：1例病灶处动脉分支增多,6例未见异常;DWI：5例均为高和（或）稍高信号,ADC图为稍高信号2例、稍低信号2例、稍高等稍低混杂信号1例;MRS：病灶区及对侧正常区均可见升高的乳酸（Lac）双峰,病灶区与对侧正常区比较Lac及Lac/Cr均明显增高（P＜0.001）.结论：MELAS型线粒体脑肌病的多模态MRI表现有一定特异性,综合分析,可提示诊断.     

Cardiac tamponade: a new complication in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes

We report the first case of cardiac tamponade in a 14-year-old female patient with an underlying illness of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient underwent a subxiphoid pericardiocentesis and pericardiotomy smoothly and was discharged with no sequelae. The coexistence of massive pericardial effusion and MELAS has never been mentioned in any literature. This case report attempts to exemplify the possibility of this connection.     

MELAS综合征MRI表现

目的:研究MELAS型线粒体脑肌病(MELAS综合征)的影像表现。材料与方法:报告一病理证实MELAS型线粒体脑肌病家族4例中的先证者的CT和MRI表现,结合文献分析该病的影像表现。结果:先证者MRI平扫见左枕、颞、顶、额叶及右枕叶大片T1WI低信号区,T2WI高信号区,DWI呈高信号,强化MRI见病灶区轻强化;MRS见NAA降低,Lac增高;同时见脑萎缩。结论:MELAS型线粒体脑肌病的MRI表现有一定的特征性。     

MELAS误诊为单纯疱疹病毒性脑炎一例

线粒体脑肌病伴高乳酸血症和卒中样发作（MELAS）是母系遗传性线粒体疾病,临床表现多样,易与单纯疱疹病毒性脑炎（HSE）混淆。该文报道1例初诊时误诊为HSE的MELAS患者,该例患者因反复发热、头痛、肢体抽搐1个月,再发头痛1周就诊,入院时初步疑诊为HSE,予以抗病毒治疗无效,进一步行血液和尿液基因检测确诊为MELAS。MELAS可与不典型的HSE表现相似,应谨慎鉴别。脑脊液和（或）血清乳酸升高和基底节钙化有助于诊断MELAS,MELAS的线粒体DNA突变可通过血液和尿液基因检测,而不需要采用肌肉活组织检查这样的有创检查。     

Mitochondrial encephalopathy, lactic acidosis and stroke-like syndrome (MELAS): a case report, presentation, and management

Mitochondrial encephalopathy with lactic acidosis and stroke-like syndrome (MELAS) is a progressive neurodegenerative disorder frequently complicated by diabetes mellitus and sensory neuronal hearing loss. This syndrome tends to present initially with stroke-like symptoms. These strokes are nonvascular in nature and are linked to mitochondrial defect such as transient oxidative phosphorylation dysfunction, which in turn results in encephalopathy. The combination of lactic acidosis, multiple nonvascular strokes, encephalopathic psychosis, diabetes, and sensory neuronal hearing loss causes severe dysfunction leading to increased mental disabilities, physical disabilities, and eventually, death.     

线粒体脑肌病伴高乳酸血症和卒中样发作误诊为脑梗死

目的探讨线粒体脑肌病伴高乳酸血症和卒中样发作的诊断要点、误诊原因及防范措施。方法对我院近期收治的误诊为脑梗死的线粒体脑肌病伴高乳酸血症和卒中样发作1例的临床资料进行回顾性分析。结果患者因双眼突发视力减退1 d入院,经查体及头颅MRI等相关检查考虑脑梗死,予相应治疗,视力稍好转。后患者行头颅数字减影血管造影及磁共振波谱检查排除脑梗死,最终经基因检查确诊线粒体脑肌病(MELAS综合征)。予改善代谢及脑供血等治疗3个月,患者病情明显好转,头颅MRI检查示病灶消失。结论临床表现与急性脑梗死相似、头颅MRI检查提示脑梗死及接诊医生知识面狭窄是导致本例误诊的主要原因。加强学习、拓宽知识面、了解并掌握线粒体脑肌病相关知识,可防止或减少其误诊。     

基底动脉尖综合征临床及影像学特点分析

目的 分析基底动脉尖综合征（TOBs）的临床及影像学特点。方法 对1998-2005年的31例确诊TOBS进行回顾性分析。结果 TOBS以意识障碍、眩晕、肢体运动障碍起病多见，合并视觉、眼球运动、偏身感觉、记忆力、计算力障碍等；影像学表现为丘脑、枕叶、小脑、中脑、颞叶等多部位梗死灶。结论 TOBS的诊断依靠临床表现及影像学检查。     

Adult-onset of Mitochondrial Myopathy,Encephalopathy, Lactic Acidosis,and Stroke-Like Episodes (MELAS) Syndrome Presenting as Acute Meningoencephalitis: A Case Report

Background: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Epileptic seizures are common features of both MELAS and meningoencephalitis and are typically treated with anticonvulsants. Objectives: To provide the reader with a better understanding of MELAS and the adverse effects of valproic acid. Case Report: A 47-year-old man with a history of diabetes, hearing loss, sinusitis, and otitis media was brought to our emergency department due to acute onset of fever, headache, generalized seizure, and agitation. Because acute meningoencephalitis was suspected, the patient was treated with antibiotics on an empirical basis. The seizure activity was aggravated by valproic acid and abated after its discontinuation. MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. Conclusion: Detailed history-taking and systematic review help emergency physicians differentiate MELAS from meningoencephalitis in patients with the common presentation of epileptic seizures. Use of valproic acid to treat epilepsy in patients suspected of having mitochondrial disease should be avoided. Underlying mitochondrial disease should be suspected if seizure activity worsens with valproic acid therapy.     

Proteomic and metabolomic advances uncover biomarkers of mitochondrial disease pathophysiology and severity

Advancing proteomic and metabolomic technologies that integrate curated omic databases have crossed a threshold to enable their clinical utility. In this issue of the JCI, Sharma et al. exploit emerging technologies to evaluate whether biomarkers identified in the mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome could refine disease characterization, uncover pathways to monitor therapeutic efficacy, and/or delineate disease-modifying targets. The authors analyzed blood and urine samples from patients with this genetic mitochondrial disease and elucidated proteins and metabolites related to NADH-reductive stress. These circulating biomarkers have intriguing clinical potential that implicate disease pathophysiology and may prove important biomarkers for the future management of MELAS.     

Cortical blindness, a rare complication of pre-eclampsia

This is a case report of a previously undiagnosed pregnant teenager who presented to the emergency department with cortical blindness. She was found to be pre-eclamptic with the HELLP syndrome. She underwent immediate cesarean section, with delivery of a viable 32-week-old infant. Computed tomography and magnetic resonance imaging studies revealed abnormalities in the occipital lobes and a possible subarachnoid hemorrhage. Her vision improved immediately after the cesarean section, and returned to normal in a few days.     

Stroke-like conditions and ischemic strokes in patients with mitochondrial diseases

Mitochondrial diseases (MD) make up a heterogenous group of pathological conditions characterized by disordered intracellular energy metabolism due to genetically determined disturbances of oxidative phosphorylation. Brain and muscles are most frequently affected in MD. Its systemic manifestations include cardiac (cardiomyopathy, arrhythmia), endocrine (diabetes), gastrointestinal, and renal disorders. This review focuses on neurologic symptoms of MD, such as stroke-like episodes (SLE) in patients with mitochondrial encephalopathy, lactic acidosis (MELAS), and ischemic stroke associated with mitochondrial cardiomyopathy and occlusive arteriopathy of main intra- and extracranial vessels. Clinical features and pathogenesis of SLE are considered along with related morphological changes in the brain, methods of laboratory and instrumental diagnosis and approaches to treatment. Mitochondrial respiratory chain and mechanisms of its' dual genetic control by nuclear and mitochondrial genomes are briefly described. Peculiarities of MD inheritance are discussed.     

Antinociceptive Effect of Stimulating the Occipital or Retrosplenial Cortex in Rats

A role for the occipital or retrosplenial cortex in nociceptive processing has not been demonstrated yet, but connections from these cortices to brain structures involved in descending pain-inhibitory mechanisms were already demonstrated. This study demonstrated that the electrical stimulation of the occipital or retrosplenial cortex produces antinociception in the rat tail-flick and formalin tests. Bilateral lesions of the dorsolateral funiculus abolished the effect of cortical stimulation in the tail-flick test. Injection of glutamate into the same targets was also antinociceptive in the tail-flick test. No rats stimulated in the occipital or retrosplenial cortex showed any change in motor performance on the Rota-rod test, or had epileptiform changes in the EEG recording during or up to 3 hours after stimulation. The antinociception induced by occipital cortex stimulation persisted after neural block of the retrosplenial cortex. The effect of retrosplenial cortex stimulation also persisted after neural block of the occipital cortex. We conclude that stimulation of the occipital or retrosplenial cortex in rats leads to antinociception activating distinct descending pain-inhibitory mechanisms, and this is unlikely to result from a reduced motor performance or a postictal phenomenon.     

Migraine and white matter hyperintensities

Patients with migraine are at increased risk for white matter hyperintensities detected on magnetic resonance imaging. The presence of nonspecific white matter hyperintensities may cause uncertainty for physicians and anxiety for patients. The pathophysiology and long-term consequences of these lesions are unknown. Occasionally, white matter lesions in a migraineur may indicate an underlying disease such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), or central nervous system vasculitis. The ability to distinguish between nonspecific and disease-specific patterns of white matter hyperintensities in migraine sufferers is important for the practicing clinician.