线粒体脑肌病1例报告并文献复习

正线粒体脑肌病(mitochondrial encephalomyopathy,ME)是线粒体功能异常导致的多系统疾病,以脑和肌肉受累最多,为遗传代谢相关性疾病,细胞核基因和线粒体基因异常均可导致其发生[1]。该病临床表现多样、各类型临床症状存在重叠,临床工作中需与其它疾病审慎辨析。本科室曾诊断线粒体脑肌病1例,现将临床资料、影像学及病理特点报告如下,并结合文献对其临床特点及辅助诊断手段进行     

成人MELAS型线粒体脑肌病误诊一例分析

目的 分析MELAS型线粒体脑肌病的临床特点及误诊原因.方法 回顾性分析1例MELAS型线粒体脑肌病的临床资料.结果 患者出现发作性抽搐,言语异常、视力下降,于当地医院误诊为脑梗死,转入首都医科大学宣武医院误诊为病毒性脑炎,后经磁共振波谱分析、及左侧肱二头肌活检诊断为MELAS型线粒体脑肌病.给予B族维生素、辅酶Q10治疗,病情缓解.结论 对于青年患者出现进行性加重的智力、听力、视力下降及肌无力癫痫发作等症状,应考虑MELAS型线粒体脑肌病的可能,进一步结合血乳酸测定、肌肉活检病理及基因检查,以及早确诊.     

线粒体脑肌病的临床特点及误诊原因分析

线粒体脑肌病目前临床上并不罕见,但其临床症状、体征及影像学表现多样,易误诊为其他神经系疾病。我院2003年8月～2004年8月收治线粒体脑肌病8例,其中6例误诊。本文回顾分析线粒体脑肌病的临床特点及误诊原因,以提高该病的早期诊断率。     

线粒体脑肌病的研究进展

线粒体脑肌病（mitochondrial encephalomyopathy）是指由线粒体基因或细胞核基因发生缺失或点突变导致的线粒体结构和功能异常,引起机体能量代谢障碍,主要累及脑和横纹肌的一类疾病。线粒体脑肌病根据临床和病理特点分为许多类型,如坏死性脑脊髓病（Leigh综合征）、卷发样脑灰质营养不良综合征（Menke病）和进行性皮层灰质萎缩症（Alpers病）、Kearne-Sayre综合征（KSS）、线粒体脑肌病并发乳酸血症和卒中样发作（MELAS）、肌阵挛瘢痫并发不整红边纤维（MERRF）、慢性进行性外眼肌麻痹（CPEO）等。笔者从该病常见类型的病理、临床表现、影像学表现及治疗等方面进行综述。     

小儿线粒体脑肌病的MRI表现及误诊分析

目的　探讨小儿线粒体脑肌病的 MRI表现及误诊原因。方法　搜集自 1996 - 0 1～ 2 0 0 0 - 12经 MRI检查 ,病理及实验室检查证实的小儿线粒体脑肌病 16例进行回顾性分析。结果　 16例脑内病灶均表现为多发对称性略长 T1 长T2 信号 ,其中单纯脑深部灰质受累 9例 ,大脑皮质和深部灰质同时受累 4例 ,2例灰白质同时受累 ,1例单纯白质受累。误诊 10例 ,其中临床误诊 4例 ,CT误诊 4例 ,MRI误诊 2例。结论　多样化的 MRI表现是小儿线粒体脑肌病的影像学特点 ,当小儿脑内深部灰质出现多发对称性异常信号 ,并能除外感染、梗塞、肝豆状核变性及神经中毒等其他疾病时 ,要考虑线粒体脑肌病的可能 ,影像与临床结合是减少误诊的措施     

一例睡眠呼吸机依赖线粒体脑肌病患者的护理

线粒体肌病(mitochondrial myopathy)和线粒体脑肌病(mitochondrial encephalomyopa-thy)是一组由线粒体或核DNA缺陷,导致线粒体结构和功能障碍、ATP合成不足所致的多系统疾病,病变以侵犯骨骼肌为主称为线粒体肌病,病变同时累及中枢神经系统则称为线粒体脑肌病.并且线粒体肌病和脑肌病可以转型,线粒体肌病可发展为线粒体脑肌病.根据临床不同症候群,临床表现复杂多样.我科于2010年8月收治了1例以睡眠时二氧化碳潴留为主要特征的患者,结合临床表现与肌电图、头MRI、胸CT等辅助检查、血清乳酸水平测定、遗传分析等诊断为线粒体脑肌病.通过积极实施个性化治疗和护理,采用了睡眠时应用无创呼吸机方式,收到了满意的效果.现将护理体会报告如下.     

MELAS综合征的影像学诊断与鉴别诊断

目的:总结线粒体脑肌病伴高乳酸血症及卒中样发作综合征的CT与MRI表现特征及与其他疾病的鉴别。方法:回顾性分析7例经肌肉病理或基因检测诊断为线粒体脑肌病伴高乳酸血症及卒中样发作综合征患者的临床及CT与MRI资料。结果:7例MRI均显示多脑叶受累,病变不按血管支配区分布,其中枕叶受累6例,顶叶受累4例,颞叶受累4例,额叶受累1例;表现为大脑皮质及皮质下多发大片状异常信号,T1WI呈等信号或低信号,T2WI及FLAIR序列呈高信号;7例中伴发基底节灰质核团受累4例,脑干受累2例、小脑萎缩1例;增强扫描少有强化。3例MRA检查均未见大血管狭窄或闭塞,1例可见大脑中动脉远端分支增多;CT扫描病变呈低密度,伴基底节区对称性钙化3例。结论:线粒体脑肌病伴高乳酸血症及卒中样发作综合征影像学表现具有一定特征性,根据临床病史及影像学表现可诊断该病的并与其他疾病鉴别,最终诊断需结合肌肉活检或DNA基因检测。     

线粒体脑肌病与癫(癎)

线粒体脑肌病是线粒体功能异常、能量来源不足而引起的一组异质性疾病,癫发作是其常见的临床症状。本文比较详细地介绍了线粒体脑肌病中癫的发生机制、临床特点、诊断及治疗,为临床工作的开展提供依据。     

乳酸酸中毒和卒中样发作综合征型线粒体脑肌病误诊分析

目的探讨乳酸酸中毒和卒中样发作综合征(MELAS)型线粒体脑肌病的临床特点及误诊原因。方法回顾性分析MELAS型线粒体脑肌病长期误诊1例的临床资料。结果本例因反应迟钝、发热3 d入院,行颅脑MRI及腰椎穿刺脑脊液等检查多次误诊为病毒性脑炎,先后行抗病毒、糖皮质激素、丙种球蛋白等治疗2年余,症状反复。后经血乳酸升高、乳酸运动试验阳性、肌肉活检病理检查确诊为MELAS型线粒体脑肌病,予相应治疗后病情明显缓解。结论 MELAS型线粒体脑肌病临床表现复杂多样,易误诊为病毒性脑炎。对病情反复发作按病毒性脑炎治疗效果不佳者应高度可疑本病,及时行血乳酸、乳酸运动试验、肌电图及肌肉活检病理检查,以帮助确诊。     

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.     

Intravitreal steroid and anti-vascular endothelial growth agents for the management of retinal vein occlusion: evidence from randomized trials

Introduction: Retinal vein occlusion (RVO) is a common retinal vascular disorder, affecting visual acuity and quality of life. Macular edema (ME) and retinal ischemia are the main causes for visual impairment in RVO. Although several modalities have been evaluated for the treatment of ME secondary to RVO in clinical trials, various questions need to be clarified when translating clinical trials into real-world practice.

Areas covered: Intravitreal steroids and anti-VEGF agents are now widely used for the treatment of ME due to RVO. Herein, evidence from randomized controlled trials regarding the use of steroids and anti-VEGF agents in ME related to RVO are presented. In addition, an approach regarding the optimal treatment regimen, the most suitable time for initiating treatment and monitoring patients, as well as the potential role of ischemia in the response to treatment and the impact of treatment on the natural course of the disease was made.

Expert opinion: A comprehensive presentation of randomized clinical trials evaluating intravitreal steroids and anti-VEGF treatment for RVO indicates that both are effective and safe. However, the comparative effectiveness of the various anti-VEGF agents, the most suitable dosing regimen and the effect of these agents on retinal ischemia remains unclear.     

Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposePrevious Phase II trials indicated clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in patients with myalgic encephalopathy/chronic fatigue syndrome (ME/CFS). The association between rituximab serum concentrations and the effect and clinical relevance of antidrug antibodies (ADAs) against rituximab in ME/CFS is unknown. We retrospectively measured rituximab concentrations and ADAs in serum samples from patients included in an open-label Phase II trial with maintenance rituximab treatment (KTS-2-2010) to investigate possible associations with clinical improvement and clinical and biochemical data.MethodsPatients with ME/CFS fulfilling the Canadian criteria received rituximab (500 mg/m²) infusions: 2 infusions 2 weeks apart (induction), followed by maintenance treatment at 3, 6, 10, and 15 months. The measured rituximab concentrations and ADAs in serum samples included 23 of 28 patients from the trial.FindingsThere were no significant differences in mean serum rituximab concentrations between 14 patients experiencing clinical improvement versus 9 patients with no improvement. Female patients had higher mean serum rituximab concentrations than male patients at 3 months (P = 0.05). There was a significant negative correlation between B-cell numbers in peripheral blood at baseline and rituximab serum concentration at 3 months (r = −0.47; P = 0.03). None of the patients had ADAs at any time point.ImplicationsClinical improvement of patients with ME/CFS in the KTS-2-2010 trial was not related to rituximab serum concentrations or ADAs. This finding is also in line with a recent randomized trial questioning the efficacy of rituximab in ME/CFS. Rituximab concentrations and ADAs still offer supplemental information when interpreting the results of these trials.     

A comparative study of Thai massage and muscle energy technique for chronic neck pain: A single-blinded randomized clinical trial

BackgroundMyofascial pain syndrome (MPS) is the most common form of muscle disorders. Traditional Thai massage (TM) and muscle energy (ME) technique have been used to treat patients with MPS for long time but head-to-head comparisons of these interventions have not been established.AimThe aim of the current study was to compare the effects of TM and the ME technique on pain intensity (PI), pressure pain threshold (PPT), neck disability (ND), and neck flexion range of motion (NFROM) in patients with chronic neck pain associated with myofascial trigger points (MTrPs).DesignA randomized, single-blinded clinical trial.SettingDepartment of Physical Therapy, School of Integrative Medicine, Mae Fah Luang University.PopulationForty-five patients with chronic neck pain associated with MTrPs were recruited.MethodsThe patients were randomly allocated to the TM, ME, or control groups, with each having eight treatment sessions over a period of two weeks. PI, PPT, ND, and NFROM were assessed before, immediately after the first treatment session, and one day after the last treatment session.ResultsBased on the results, both TM and the ME technique resulted in a significant improvement in all parameters (p < 0.05) compared to the control group. Additionally, no significant difference was observed between TM and the ME technique in all parameters.ConclusionsThe application of TM or the ME technique can be a practical alternative approach for the treatment of chronic neck pain associated with MTrPs.     

Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.     

颌面部肌上皮瘤的MSCT诊断及文献复习

目的 探讨颌面部肌上皮瘤(ME)的MSCT影像特点.方法 对30例经手术病理证实的颌面部ME患者的MSCT平扫及增强特征进行回顾性分析.结果 30例ME均表现为类圆形或椭圆形结节,多数(25例)病灶直径1.0～2.5 cm,部分病灶内可见囊变(21例)及包膜(12例),少数(4例)病灶内可见钙化,平扫密度均匀或不均匀;增强扫描动、静脉期均显著强化,并有向心性强化的趋势.结论 颌面部ME的MSCT表现具有特征性,MSCT对ME的诊断具有重要价值.     

Using a Morphine Equivalence Metric to Quantify Opioid Consumption: Examining the Capacity to Provide Effective Treatment of Debilitating Pain at the Global,Regional, and Country Levels

ContextMorphine has been considered the gold standard for treating moderate-to-severe pain, although many new opioid products and formulations have been marketed in the last two decades and should be considered when examining opioid consumption. Understanding opioid consumption is improved by using an equianalgesic measure that controls for the strengths of all examined opioids.ObjectivesThe research objective was to use a morphine equivalence (ME) metric to determine the extent that morphine consumption relates to the total consumption of all other study opioids.MethodsAn ME metric was created for morphine and the aggregate consumption of each study opioid (Total ME), adjusted for country population to allow for uniform equianalgesic comparisons. Graphical and statistical evaluations of morphine use and Total ME consumption trends (between 1980 and 2009) were made for the global and geographic regional levels and selected developed and developing countries.ResultsGlobal morphine consumption rose dramatically in the early 1980s but has been significantly outpaced by Total ME since 1996. As expected, the extent of morphine and Total ME consumption varied notably among regions, with the Americas, Europe, and Oceania regions accounting for the highest morphine use and Total ME in 2009. Developing and least developed countries, compared with developed countries, demonstrated lower overall Total ME consumption.ConclusionGenerally, worldwide morphine use has not increased at the rate of Total ME, especially in recent years. Examining a country's ability to effectively manage moderate-to-severe pain should extend beyond morphine to account for all available potent opioids.     

How do we reduce acyclovir overuse? Impact of FilmArray meningitis/encephalitis panel tests for pediatric patients

BackgroundFew Japanese hospitals can perform in-house cerebrospinal fluid (CSF) polymerase chain reaction (PCR) to screen for herpes simplex virus, leading to patients being administered acyclovir (ACV) for several days. The FilmArray Meningitis/Encephalitis Panel (ME Panel) is a multiplex PCR test that can identify 14 major pathogens within 1 h. We aimed to investigate the efficacy of the ME Panel in children admitted with central nervous system infections in Japan.MethodsWe conducted a single-center, quasi-experimental study. The ME panel was introduced in April 2020. We outsourced the CSF samples to a laboratory during the pre-intervention period (April 2016 to March 2020) and performed the ME panel at our hospital during the post-intervention period (April 2020 to December 2021). Duration and dose of ACV and antibiotic use, length of stay (LOS) in the pediatric intensive care unit (PICU), and total LOS after testing were compared using the Mann-Whitney U test.ResultsThe number of cases in the pre- and post-intervention periods was 67 and 22 cases, respectively. The median duration of ACV decreased significantly from 6 days to 0 day (p < 0.001), and the median dose of ACV use decreased significantly from 14 vials to 0 vial (p < 0.001). No significant differences were noted in the total duration and dose of antibiotic use, LOS in PICU, and the total LOS after testing.ConclusionThe introduction of ME panel may contribute to appropriate ACV use; however, there was no significant change in the duration and dose of antibiotic use or LOS.     

Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules

PurposeMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisymptom illness impacting up to 1 million people in the United States. As the pathogenesis and etiology of this complex condition are unclear, prospective treatments are limited. Identifying US Food and Drug Administration–approved drugs that may be repositioned as treatments for ME/CFS may offer a rapid and cost-effective solution.MethodsHere we used gene-expression data from 33 patients with Fukuda-defined ME/CFS (23 females, 10 males) and 21 healthy demographically comparable controls (15 females, 6 males) to identify differential expression of predefined gene-module sets based on nonparametric statistics. Differentially expressed gene modules were then annotated via over-representation analysis using the Consensus Pathway database. Differentially expressed modules were then regressed onto measures of fatigue and cross-referenced with drug atlas and pharmacogenomics databases to identify putative treatment agents.FindingsThe top 1% of modules identified in males indicated small effect sizes in modules associated with immune regulation and mitochondrial dysfunction. In females, modules identified included those related to immune factors and cardiac/blood factors, returning effect sizes ranging from very small to intermediate (0.147 < Cohen δ < 0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor α, transforming growth factor β, and metabolic and cardiac modules were strongly correlated with multiple composite measures of fatigue. Cross-referencing identified genes with pharmacogenomics data indicated immunosuppressants as potential treatments of ME/CFS symptoms.ImplicationsThe findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation–based treatment strategies.