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中国妇儿医学影像论坛，旨在为热爱妇产科、儿科的临床医生、影像科医生及相关专业同行搭建学术交流平台，现已增建2群，我们的目标是成为中国最好的妇儿影像交流论坛群！在这里，您可以参与精彩的病例讨论、了解妇儿影像最新进展、获取相关会议信息。感谢您的加入！交流、共享、学习、提高！ 主题月讨论 杨朝湘 06:01 今天继续主题月第二期读片
杨朝湘 06:01 Case 1
杨朝湘 06:01 
杨朝湘 06:02 13岁男孩。临床出现乳酸酸中毒和卒中样症状。
A为DWI，B为ADC图，C为动脉自旋标记伪彩图。
杨朝湘 06:02 Case 2
杨朝湘 06:02 
杨朝湘 06:02 8岁女孩，癫痫、下肢痉挛。
A为T2WI，B为短TE MRS，C为长TE MRS；D为3个月后复查T2WI，E为复查短TE MRS，F为复查长TE MRS。
杨朝湘 06:02 Case 3
杨朝湘 06:02 
杨朝湘 06:03 6岁女孩
A为T2WI，B为T2 FLAIR
杨朝湘 06:03 以上三例答案在以下选项中：
A、Kearns-Sayre综合征
B、Hallervorden-Spatz综合征
C、丙酸血症
D、Leigh综合征
E、MELAS综合征
F、Fahr病
杨朝湘 18:15 公布早读答案：
杨朝湘 18:15
杨朝湘 18:15 Case 1 MELAS综合征
杨朝湘 18:16 文中图注：Scattered foci of vasogenic edema corresponding to increased perfusion are identified in the acute phase of the disease in the right cerebral hemisphere.
疾病急性阶段，于右侧大脑半球可见散在局灶性血管源性水肿灶，病灶内灌注增加。
杨朝湘 18:16 关于MELAS（Case 1）的caffey讲解：
杨朝湘 18:16 Several clinical syndromes arising from point mutations in mtDNA are encountered. The most noticeable are MELAS syndrome, MERRF syndrome, neurogenic weakness and ataxia with retinitis pigmentosa syndrome, and Leber hereditary optic neuropathy.
临床上有多个综合征是由mtDNA点突变引起。其中最值得注意的有MELAS综合征、MERR F综合征、神经源性虚弱和共济失调并色素性视网膜炎综合征及Leber遗传性视神经病。
MELAS syndrome often is caused by an A3243G point mutation in tRNA-leuUUR or the MTTL1 gene (80% of cases). The clinical presentation of MELAS syndrome resembles that of cerebral infarction; however, the “infarcts” are affected without the usual arterial stroke patterns. Age of onset is usually between 2 and 11 years. The basal ganglia and parietal and occipital lobes are most commonly involved. Cerebral MRI demonstrates areas of hyperintensity on T2-weighted images with volume loss presenting as a late development.
MELAS综合征常由tRNA-leuUUR或MTTL1基因的A3243G点突变引起。MELAS综合征的临床表现类似于脑梗死。其发病年龄通常在2-11岁。基底节和顶枕叶最常受累。到病变晚期，颅脑MRI可见病变区呈T2高信号，并伴脑萎缩。
Proton MRS has been used to aid diagnosis of mitochondrial disorders, with the assumption that elevation of lactic acid is a primary feature. However, positive lactate at spectroscopy does not necessarily equal the presence of a mitochondrial disorder, and the absence of lactate on MRS does not rule out a defect in mitochondrial function. Proton MRS in patients with MELAS syndrome can demonstrate variable results as strokelike lesions emerge and evolve.
MRS有助于线粒体病的诊断。主要是乳酸峰的增高可提示诊断。但是出现乳酸峰增高并不意味着就是线粒体病，而没有乳酸峰增高也不能就完全排除线粒体病。在MELAS综合征病人卒中样症状发作到缓解消失的不同时期，MRS表现可有很大不同。
Proton MRS details energy failure with increased lactate and decreased creatine. Elevation of lactate in the acute and subacute stages typically is observed, with subsequent declines in NAA and creatine, consistent with neuroaxonal injury that may or may not be reversible. It has been reported that both increase of lactate peaks in MRS and state of hyperperfusion in continuous arterial spin labeling images are both indicative of active lesions.
MRS出现乳酸峰增高和肌酸峰下降，提示能量代谢障碍。在MELAS综合征的急性期和亚急性期都可见到乳酸峰增高，
杨朝湘 18:17
杨朝湘 18:17 Case 2 Leigh综合征
杨朝湘 18:18 图注：The imaging reveals a pattern characteristic of “Leigh syndrome” with an abnormal hyperintense signal bilaterally within the caudate and globus pallidus. The MRS image acquired in the left basal ganglia at a period of clinical exacerbation caused by febrile illness demonstrates a dramatic elevation of lactate compared with her routinely observed levels as shown in axial T2-weighted (D), short echo MRS (E), and long echo MRS (F) images. The spectra acquired 3 months later demonstrates a significant reduction in lactate. A comparison of the imaging data is unremarkable between the examinations. The dramatic elevation of lactate revealed on MRS in Band C corresponds to worsening clinical symptoms (seizures and leg stiffening). The lactate levels observed in E and F are typical and consistent with this mitochondrial defect.
典型Leigh病MRI表现，即双侧尾状核和苍白球异常高信号。临床发热重症期MRS（左侧基底节采样）所示乳酸峰显著高于3个月后一般病情期MRS所示。3个月后的MRS乳酸峰虽相对较低，但仍符合典型线粒体病的表现。两次的T2WI表现无明显差异。
杨朝湘 18:19 关于Leigh Syndrome (Case 2)
Disorders arising from defects in nDNA are numerous; however, the most commonly encountered syndrome is Leigh syndrome. The genetic defect of Leigh syndrome can arise from several sources, including pyruvate dehydrogenase complex deficiency, complex I deficiency, complex V deficiency with adenosine triphosphatase 6 mutation, and cytochrome oxidase deficiency with SURF1 mutation.
许多疾病源自nDNA缺陷，最常见的是Leigh综合征。Leigh综合征的基因缺陷有几个来源，包括丙酮酸脱氢酶复合体缺陷、复合体Ⅰ缺陷、复合体Ⅴ缺陷并三磷酸腺苷酶6突变，以及 细胞色素氧化酶缺陷并SURF1突变。
This group of disorders characteristically presents at 3 months to 2 years of age but may begin with symptoms of hypotonia in the newborn period or even in adulthood. Clinical signs include ophthalmoplegia, cerebellar signs, and spasticity, which are slowly progressive. Other features include psychomotor regression, extrapyramidal signs, blindness, nystagmus, respiratory compromise, or cranial nerve palsies. Onset of symptoms within the first years of life typically portends a rapid downhill course. A later onset of symptoms is generally associated with slower progression
这组疾病典型发病年龄为3个月到2岁。但可在新生儿期甚或成人后出现肌张力减低。临床症状包括逐渐进展的肌肉痉挛、眼肌麻痹和小脑症状。还可出现精神运动发育倒退、锥体外系症状、失明、眼球震颤、呼吸功能损害或颅神经麻痹。常在1岁内发病并迅速恶化。而若发病年龄较大，则病情进展一般会较慢。
Pathologically, this syndrome involves both gray and white matter of the brain and spinal cord. Common sites of anatomic involvement include the basal ganglia, specifically the globus pallidus and putamina, and the thalami, midbrain, pons, cerebellum, and medulla. Pathologic changes include spongiform degeneration, demyelination, and vascular compromise/proliferation.
病理上，Leigh综合征可累及脑和脊髓的灰质和白质。常受累的神经系统结构包括：基底节（尤其是苍白球和壳核）、丘脑、中脑、桥脑、小脑和延髓。病理改变包括：海绵样变性、脱髓鞘和血管损害/增生。
杨朝湘 18:19 An abnormal low signal on T1-weighted images or a high signal on T2-weighted images in the basal ganglia, periaqueductal gray matter, and brainstem/cerebellum are characteristic of this group of disorders. Bilateral symmetric lesions in the basal ganglia (globus pallidus and putamen) characterized by a hypointense signal on T1-weighted images and a hyperintense signal on T2-weighted images is highly suggestive of this condition and should prompt further clinical investigation for signs of lactic acid in the serum or CSF. Late involvement may manifest as regions of an abnormal hyperintense signal on T2-weighted images in the centrum semiovale.
Leigh综合征MRI表现为，基底节、中脑导水管周围灰质和脑干/小脑在T1WI上呈异常低信号，而在T2WI上呈高信号。双侧基底节（苍白球和壳核）对称性受累较具特征性。可据此提示临床进一步查血清或脑脊液乳酸浓度。晚期可累及半卵圆中心而出现T2WI异常高信号。
Proton MRS images obtained from the basal ganglia, occipital cortex, and brainstem show elevations in lactate, which are most pronounced in regions where abnormalities are seen with routine T2-weighted MRI. Proton MRS images in regions of abnormal MRI signal also reveal a decrease in the NAA/creatine ratio and an increase in the choline/creatine ratio, representing neuronal loss and breakdown of membrane phospholipids. Some evidence indicates that a reduction of lactate levels may correlate with response to therapy, such as dichloroacetate and coenzyme Q10.
MRS可于基底节、枕叶和脑干采样。其最具诊断价值的表现为T2WI异常信号区采样的MRS上出现乳酸峰增高。此外，还可出现NAA/肌酸比值下降和胆碱/肌酸比值升高，提示神经元缺失和膜磷脂崩解。有研究表明，乳酸峰可在相关治疗（如二氯乙酸盐和辅酶Q10）后下降。
杨朝湘 18:20
杨朝湘 18:20 Case 3 Hallervorden-Spatz综合征
杨朝湘 18:20 Case 3图注： pantothenate kinase-associated neurodegeneration or neurodegeneration with brain iron accumulation, traditionally referred to as Hallervorden-Spatz syndrome. An abnormal hypointense signal is demonstrated bilaterally in the globus pallidus.
泛酸激酶相关神经退行性变，或神经退行性变伴脑内铁沉积。传统上又称之为Hallervorden-Spatz综合征。MRI表现为双侧苍白球异常低信号。
杨朝湘 18:21 Pantothenate Kinase-Associated Neurodegeneration (Case 3)
Pantothenate kinase-associated neurodegeneration, also called neurodegeneration with brain iron accumulation (NBIA), is caused by mutations in the gene that encodes pantothenate kinase 2 (PANK2). PANK2 is necessary for the production of coenzyme A in mitochondria. Other similar mutations result in atypical presentations of the same syndrome. “Classic” NBIA has an early onset of disease in infancy, with rapid progression of gait impairment, development of choreoathetoid movements, rigidity, dysarthria, and cognitive decline. Dystonia is a prominent feature of this disorder. All of these clinical manifestations reflect the impact of the disease upon the basal ganglia and striatum. Atypical NBIA has a later presentation with slower progression
泛酸激酶相关神经退行性变，又称神经退行性变伴脑内铁沉积(NBIA)，是由编码泛酸激酶2(PANK2)的基因发生突变引起。PANK2为合成线粒体内辅酶A所必需。典型NBIA可在婴儿期发病，并迅速进展。临床可出现步态异常、手足徐动症、刻板动作、构音障碍和认知能力下降。肌张力障碍是该病的一个突出特点。所有的临床症状都反映病变损害了基底节和纹状体。不典型的NBIA可发病较晚，且临床进展较慢。
杨朝湘 18:21 这三例均归类于“线粒体病”，关于线粒体病，Ｃaffey有如下讲解：
杨朝湘 18:22 Mitochondrial Diseases （线粒体病）
Mitochondrial diseases generally refer to disorders of the mitochondrial respiratory chain, the only cellular metabolic pathway under control by both the mitochondrial genome (mtDNA) and the nuclear genome (nDNA). Mitochondrial diseases demonstrate impaired respiratory chain function and reduced adenosine triphosphate production.
线粒体病是指线粒体呼吸链病变。呼吸链是唯一由线粒体基因组(mtDNA)和核基因组(nDNA)共同调控的细胞代谢途径。线粒体病可致呼吸链功能障碍及三磷酸腺苷合成减少。
The mtDNA mutations can be divided into two categories: those that impair mitochondrial protein synthesis in toto and those that affect respiratory chain subunits. Disorders attributed to mtDNA mutations follow lax rules of mitochondrial genetics. However, disorders arising from nDNA mutations are governed by Mendelian genetics. The disorders attributed to mutations in nDNA are more abundant because most respiratory chain subunits are nucleus-encoded and the correct assembly and functioning of the entire respiratory chain require numerous steps.
mtDNA突变可分为两类：一类导致线粒体蛋白合成完全缺失，另一类是影响呼吸链亚单位。源自mtDNA突变的疾病遵循较宽松的遗传学规则；而源自nDNA突变的疾病则遵循孟德尔遗传学规则。源自nDNA突变的疾病的种类更多，这是因为大多数呼吸链亚单位由细胞核编码并合成，并且完整的呼吸链功能需要一系列的步骤。
The clinical phenotypes of nDNA-related mitochondrial disorders tend to be uniform, whereas both the spectrum and severity of clinical manifestations associated with mtDNA-related disorders are extremely variable. Marked genotype-phenotype variability is characteristic of mtDNA-related disorders. The clinical diversity observed in patients with mtDNA-related disorders can be partially explained by heteroplasmy, the coexistence of mutant and wild-type mtDNA within a cell. Only when the proportion of mutant genomes exceeds a particular level is the disease expressed (threshold effect).
nDNA相关线粒体病的临床表型较为一致。而mtDNA相关疾病则无论疾病谱，还是临床表现的严重程度，各病种间可有显著的不同。显著的基因型-表型差异是mtDNA相关疾病的一个特点。之所以mtDNA相关疾病能表现出这样明显的临床多样性，部分要归因于其异质性，即在一个细胞内同时存在突变型和野生型mtDNA。只有当突变基因比例超过某一特定水平后才能致病（阈值效应）。
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