儿童神经先天性代谢异常：临床与影像要点

Congenital Inborn Errors of Metabolism: Clinical and Imaging Pearls | Normal myelination progression | Hypomyelination disorders | Myelination less than expected for age | T1 - white matter isointense or slightly hypointense to gray matter | T2 - white matter hyperintense to gray matter | Gerike SK et al. Published online: January 16, 2025 | https://doi.org/10.1148/rg.240053 | RadioGraphics

遵义市第一人民医院 | 遵义医科大学第三附属医院 | 儿童神经先天性代谢异常：临床与影像要点 | Congenital Inborn Errors of Metabolism: Clinical and Imaging Pearls | 汇报人：杨 莉 | 主持人：江 林 | 团结 专业 务实 进取

放射科住培基地共读文献2025 | 美浮一区杂志 | 佛统一起成长 | 概述 | ➢儿童神经先天性代谢异常（Inborn Errors of Metabolism，IEM）：由于先天性代谢性缺陷（基因突变引起酶缺陷、细胞膜功能异常或受体缺陷），从而导致机体生化代谢紊乱，造成中间或旁路代谢产物蓄积，或终末代谢产物缺乏，从而引起中枢神经系统症状和体征的一组疾病 | ➢多数为常染色体隐性遗传，少数为显性或X连锁遗传 | ➢发病率：国际遗传代谢病分类记载的IEM已逾1450种，总体发病率约1/800-1500活产婴，约25%新生儿期发病 | ➢临床分类（按代谢产物）：氨基酸、脂肪酸、有机酸、线粒体、溶酶体、碳水化合物、过氧化物酶体和金属等

放射科住培基地共读文献2025 | 美浮一区杂志 | 佛统一起成长 | 概述 | ➢IEM影像学评估具有挑战性，这源于其代谢异常的复杂性、临床表现的多样性以及影像学表现的异质性 | ➢婴儿期症状：脑病、喂养困难、肌张力低下、发育迟缓、癫痫、生长停滞等 | ➢临床诊断线索：包括无并发症的分娩后迅速恶化、父母近亲结婚、兄弟姐妹有代谢异常病史或不明原因死亡、畸形特征及肝脾肿大等 | ➢第一部分概述IEM分类，将其分为能量产生障碍（如线粒体疾病）、复杂分解和合成过程障碍（如溶酶体贮积症和过氧化物酶体生物合成障碍）以及导致毒性代谢物积累的细胞通路障碍（如尿素循环障碍、氨基酸代谢病和有机酸血症），重点介绍了可以缩小鉴别诊断范围的临床和影像学特征，这些特征包括基于细胞器功能障碍、实验室标志物、临床表现和影像学模式的分类 | ➢第二部分重点讨论了九种必须掌握的儿童神经代谢疾病的临床表现和影像学特征

放射科住培基地共读文献2025 | 美浮一区杂志 | 佛统一起成长 | 影像检查方案 | ➢新生儿期可采用超声（US）作为筛查工具，以排除脑积水、颅内出血等脑病病因，可显示代谢疾病的非特异性标志物，如生发层囊肿 | ➢MRI是儿童神经代谢性疾病检查的金标准 | ➢采用三平面T2显示受累解剖结构，矢状面用于更好地评估脑干受累 | ➢SWI用于评估钙化、矿化和出血 | ➢MRS选取中等TE（135或144ms），主要用于评估乳酸和甘氨酸水平 | Table 1: MRI Protocols for Neurometabolic Disorders in Neonates and Children Older than 6 Months | Neonates and infants aged up to 6 months | Axial T1-weighted imaging (3-mm section width) | Axial T1-weighted 3D gradient-echo imaging with reformatting | Axial, coronal, and sagittal T2-weighted imaging (3 mm) | Axial SW imaging | Multiplanar DW imaging | Single-voxel MR spectroscopy (135-msec echo time with voxel centered on left or right basal ganglia) | Infants older than 6 months | Sagittal T1-weighted 3D gradient-echo imaging with reformatting | Axial FLAIR imaging (3-mm section width) | Axial, coronal, and sagittal T2-weighted imaging (3 mm) | Axial SW imaging | Multiplanar DW imaging | Single-voxel MR spectroscopy (135-msec echo time with voxel centered on left or right basal ganglia) | Note.—DW = diffusion weighted, FLAIR = fluid-attenuated inversion recovery, SW = susceptibility weighted, 3D = three dimensional.

放射科住培基地共读文献2025 | 美浮一区杂志 | 佛统一起成长 | 神经代谢疾病的分类 | 神经代谢性疾病分类 | 细胞器功能障碍 | 线粒体疾病 MELAS、Leigh综合征、PDH缺乏症等 | 溶酶体贮积症 MLD、克拉伯病、MPS等 | 过氧化物酶体疾病 X-ALD、Zellweger综合征 | 实验室标志物 | 乳酸升高 提示线粒体疾病 | 氨升高 尿素循环障碍及有机酸血症 | 艾链基肉碱升高 MSUD | 甘氨酸升高 NKU | 临床表现 | 异常头围 | 小头畸形 PMD | 巨头畸形 亚历山大病、Canavan病 | 病史 | 起病缓慢（也有急性加重） | 无明产期或血缘史 | 新生儿期性脑病 | 氨基酸、有机酸、脂肪酸代谢异常及线粒体能量障碍等 | 影像模式 | 增强模式 | 髓鞘周围强化、脱髓鞘的强化 | MRS | 注意特征性代谢峰 | 髓鞘发育不良 PMD | 灰白质同时受累 | 白质受累 | 皮层下U质受累、中央白质受累、前后梯度变化 | 灰质受累 | 皮质受累、深部灰质核团受累

Table 2: Key Laboratory and Clinical Clues to Pediatric Neurometabolic Disorders | Clue(s) | Associated Neurometabolic Disorder(s) | Laboratory markers | Elevated lactate level(s) (think mitochondrial disorders) | MELAS, Leigh syndrome, PDH deficiency, COX deficiency | Elevated ammonia level(s) (think urea cycle defects and organic acidopathies) | Citrullinemia, propionic acidemia, methylmalonic acidemia, glutaric aciduria type I | Elevated BCAA level(s) | MSUD | Elevated glycine level(s) | NKH | Clinical features | Neonatal metabolic encephalopathy | MSUD, NKH, citrullinemia, PDH deficiency, Zellweger spectrum disorder, molybdenum cofactor deficiency | Microcephaly | Pelizaeus-Merzbacher disease, Cockayne disease, Aicardi-Goutières disease | Macrocephaly | Canavan disease, Alexander disease, glutaric aciduria type 1 | Note.—BCAA = branched chain amino acid, COX = cytochrome c oxidase, MELAS = mitochondrial encephalopathy with lactic acidosis and strokelike episodes, MSUD = maple syrup urine disease, NKH = nonketotic hyperglycinemia, PDH = pyruvate dehydrogenase.

表2：儿科神经代谢性疾病的关键实验室和临床线索 | 线索 | 具体线索 | 关联的神经代谢性疾病 | 实验室标志物 | 乳酸水平升高（考虑线粒体疾病） | MELAS、Leigh综合征、PDH缺乏症、细胞色素C氧化酶缺乏症 | 血氨水平升高（考虑尿素循环障碍和有机酸血症） | 瓜氨酸血症、丙酸血症、甲基丙二酸血症、戊二酸尿症1型 | 支链氨基酸水平升高 | 枫糖尿症(MSUD) | 甘氨酸水平升高 | 非酮性高甘氨酸血症(NKH) | 临床特征 | 新生儿代谢性脑病 | 枫糖尿症、非酮性高甘氨酸血症、瓜氨酸血症、PDH缺乏症、Zellweger谱系疾病、钼辅因子缺乏症 | 小头畸形 | Pelizaeus-Merzbacher病、Cockayne病、Aicardi-Goutières病 | 巨头畸形 | Canavan病、Alexander病、戊二酸尿症1型

细胞器功能障碍——线粒体疾病 (Mitochondrial Disorders) | 线粒体是存在于真核细胞胞质内的细胞器，通过呼吸链（或称电子传递链）参与能量生产。该链由复合物I-IV与辅酶Q及细胞色素C共同构成（图1） | 任何影响呼吸链功能的突变均可导致线粒体功能障碍。这类疾病主要累及高代谢需求的组织，包括脑组织、肌肉及心肌组织 | 典型的线粒体疾病包括：线粒体脑肌病伴乳酸酸中毒和卒中样发作（MELAS）、Leigh综合征、丙酮酸脱氢酶（PDH）缺乏症、细胞色素C氧化酶缺乏症 | Figure 1. Diagram of a mitochondrion and the respiratory transport chain.

细胞器功能障碍——溶酶体贮积症 (Lysosomal Storage Disorders) | 溶酶体贮积症是由溶酶体功能缺陷引起的一类疾病 | 溶酶体作为膜性细胞器，其内含有多种酶，负责分解和回收大分子物质（如复合脂质、脂蛋白和黏多糖）、细胞碎片以及病毒和细菌病原体 | 典型病例包括：异染性脑白质营养不良(MLD)、克拉伯病、单唾酸神经节苷脂2型（GM2）神经节苷脂贮积症，以及黏多糖贮积症（MPS） | Figure 3. Drawing illustrates lysosomal function. Lysosomes are produced by the Golgi apparatus and contain enzymes that break down macromolecules, cellular debris, and pathogens. The lysosomes fuse with a vacuole containing particles for breakdown, which are then broken down by lysosomal enzymes released from the cell by way of exocytosis.

细胞器功能障碍——过氧化物酶体疾病 (Peroxisomal Disorders) | 过氧化物酶体是具膜包被的细胞内细胞器，通过内质网增殖或成熟过氧化物酶体出芽产生 | 过氧化物酶体含有特定的膜结合蛋白，这些蛋白在合成和分解代谢过程中至关重要，负责降解极长链脂肪酸、促进胆汁盐生成以及清除自由基 | 过氧化物酶体疾病的典型代表包括Zellweger谱系疾病和X连锁肾上腺脑白质营养不良（X-ALD） | Figure 4. Drawing illustrates peroxisomal function. Peroxisomes are membrane-bound intracellular organelles produced from the endoplasmic reticulum or by means of budding from mature peroxisomes. When damaged, peroxisomes undergo degradation by means of a process called pexophagy.

Organelle dysfunction | Mitochondrial disorders | Lysosomal storage disorders | Peroxisomal biosynthesis disorders | MELAS Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes OMIM 590050 | Leigh syndrome OMIM 256000 | MLD Metachromatic leukodystrophy OMIM 250100 | Krabbe disease OMIM 245200 | X-ALD X-linked adrenoleukodystrophy OMIM 300100 | PDH Pyruvate dehydrogenase deficiency OMIM 300502 | COX deficiency Cytochrome c oxidase (COX) deficiency OMIM 220110 | GM2 gangliosidosis OMIM 272800 | MPS Mucopolysaccharidosis OMIM 309900 | Zellweger syndrome OMIM 214100

MRS ➤1.5T采用中等TE（135-144ms），3.0T采用长TE（288ms） ➤提示特定诊断的异常代谢峰包括： ① 线粒体疾病：1.3ppm Lac峰 ② NKH：3.56ppm 甘氨酸峰 ③ Canavan病：NAA峰升高，NAA/Cho比值增加 ④ MSUD：0.9ppm支链氨基酸（BCAA）峰 ⑤ 肌酸缺乏症：3.0ppm 处的肌酸（Cr）峰缺失或降低 MR spectroscopy Spectra metabolites and changes with age NAA: 2.0 ppm Cr: 3.0 ppm Cho: 3.2 ppm Single voxel MRS　Spectra changes with age　Lactate peak Right basal ganglia　Right periventricular white matter　Neonatal spectra　Adult spectra　1.3 ppm Abnormal spectra suggestive of a specific diagnosis Non-ketotic hyperglycinemia　Canavan disease　Maple syrup urine disease　Creatine deficiency disease Glycine peak at 3.56 ppm　Elevated NAA peak / Increased NAA:Cho ratio　BCAA peak at 0.9 ppm　Absent/reduced Cr peak at 3.0 ppm

强化模式 ➤强化模式有助于缩小鉴别诊断范围 ➤亚历山大病：邻近脑室周围强化，额角「帽征」 ➤X连锁肾上腺脑白质营养不良（X-ALD）：活动性脱髓鞘及炎症前缘的强化 Enhancement pattern Periventricular enhancement　Enhancement of leading edge of active demyelination and inflammation Alexander disease　X-linked adrenoleukodystrophy

枫糖尿病（Maple Syrup Urine Disease, MSUD） ➤MSUD是一种罕见的常染色体隐性遗传疾病，患病率为1/185000 ➤发病机制：由于编码支链α-酮酸脱氢酶复合物(BCKDC)的基因发生突变引起 ➤相对好发于新生儿期，因患儿尿液、体味中发现特殊的枫糖浆气味而得名 ➤分5型：经典型(新生儿型，最常见)、中间型、间歇型、维生素B1反应型及二氢脂酰脱氢酶缺乏型(罕见) ➤临床表现：新生儿早期可表现为喂养不良、呕吐、酮症酸中毒、低血糖、嗜睡和癫痫发作 Leucine　Isoleucine　Valine Branched-chain aminotransferase α-Ketoglutarate　Glu KIC　KMV　KIV BCKDK PPM1K E1α E1β　E2　E3 Isovaleryl-CoA　α-Methylbutyryl-CoA　Isobutyryl-CoA Acetyl-CoA + acetoacetate　Acetyl-CoA + succinyl-CoA　Succinyl-CoA

枫糖尿病（Maple Syrup Urine Disease, MSUD） ➤MSUD有两种不同水肿表现 新生儿期MUSD水肿 ├─ 特异性水肿 │ ├─ 多好发于新生儿的髓鞘化白质区域，涉及小脑白质、脑干、丘脑、内囊后支、半卵圆中心区域 │ └─ 在髓鞘化的白质区域由于神经递质紊乱，如谷氨酸酯和乳酸盐的增加、髓磷脂脂质和髓磷脂蛋白的合成减少，造成水分子扩散运动受限，产生了细胞毒性水肿 └─ 弥漫性水肿 ├─ 多好发于新生儿期尚未髓鞘化的白质区域，涉及皮层下白质、额叶白质、枕叶白质、颞叶白质 └─ 在未髓鞘化的区域，由于血脑屏障的改变，水分子的扩散能力增强，使细胞外间隙的总体水增加，呈血管源性水肿表现，在ADC上呈高信号

MSUD影像表现 ➤病理：在出生时已髓鞘化或正在髓鞘化发育的区域髓鞘内水肿 ➤特点：与新生儿大脑的髓鞘化进程部位相一致（因为代谢异常产物最容易累及髓鞘发育成熟或快速区域） ➤特征性「4点成像外观」：2个位于腹外侧的「点」代表皮质脊髓束受累，2个位于背侧的「点」代表中央被盖束受累 ➤信号异常：脑白质弥漫性脑水肿，呈长T1长T2信号，DWI信号可逆：急性期高信号，缓解期恢复 ➤特征性MRS：在0.9ppm处可发现一个相对特异性的宽峰（因氧化脱羧作用异常所造成的支链氨基酸和支链α—酮酸上甲基质子聚集所形成） ➤鉴别诊断：缺血缺氧性脑病、非酮症高甘氨酸血症（NKH）

枫糖尿病（Maple Syrup Urine Disease, MUSD） • Figure 12.MSUD in a 5-day-old male neonate with poor feeding, vomiting, and increasing lethargy(嗜睡). • (A–C) Axial T2-weighted MR images show marked edema (arrows) involving the central white matter (A), posterior limbs of the internal capsule bilaterally (B), and brainstem and cerebellum (C). • (D–F) Axial diffusion weighted MR images show restricted diffusion involving areas of active myelination, including the perirolandic region (D), posterior limbs of the internal capsules (E), and brainstem (F), with the characteristic four-dot appearance (arrows).

亚历山大病 (Alexander Disease, AxD) ▶亚历山大病(AxD)是一种罕见的常染色体显性遗传病,由胶质纤维酸性蛋白(GFAP)基因突变所致 ▶病理学特征:星形胶质细胞胶质纤维酸性蛋白(GFAP)的大量累积和Rosenthal纤维的形成 ▶临床分型:发病越早,病情越重 ✓I型(60%)发病较早,通常小于4岁(婴儿型),巨头畸形、发育迟缓、癫痫等 ✓II型(40%):多见于4岁后(青少年+成人型),脑干症状为主,表现为共济失调、延髓/假性延髓麻痹和癫痫发作等

AxD影像表现 ▶总体特点:白质病变从前向后发展,累及皮质下弓状纤维,巨头畸形(婴儿型) ▶白质病变:以额叶为主的对称性白质异常信号(T1低信号、T2/FLAIR高信号) ▶脑室周围强化:增强扫描可见侧脑室额角周围"帽状"强化(特征性表现) ▶深部灰质受累:基底节、丘脑信号异常 ▶脑干与脊髓:延髓、颈髓萎缩呈"蝌蚪征"(尤其成人型) ▶鉴别诊断:伴皮质下囊肿的巨脑性白质脑病(MLC)、Canavan病、异染性脑白质营养不良(MLD)

Figure 13. Alexander disease in a 12-month-old girl with macrocephaly, seizures, developmental delay, and spasticity. (A)Axial T2-weighted MR image shows symmetric white matter signal intensity abnormality with a frontal predominance (arrow) and involvement of the subcortical arcuate fibers. There is also symmetric hyperintensity within the basal ganglia (arrowheads) and thalami (*). (B)Axial contrast-enhanced T1-weighted MR image shows periventricular enhancement adjacent to the frontal horns of the lateral ventricles (arrows), also known as frontal horn caps. (Case courtesy of Susan Blaser, MD, FRCPIC], Hospital for Sick Children, Toronto, ON, Canada.)

Figure 14.Alexander disease in a 9-year-old girl with vomiting and failure to thrive. (A) Axial FLAIR MR image shows symmetric white matter signal intensity abnormality with a frontal predominance (short arrow) (anterior-to-posterior gradient [long arrow]). However, unlike in the infantile-onset case in Figure 13, there is relative sparing of the subcortical arcuate fibers. Symmetric hyperintensity within the basal ganglia (arrowheads) and thalami (*) is noted. (B) Axial T2-weighted MR image shows a masslike hyperintense lesion (arrowhead) within the dorsal right aspect of the medulla. (C) Axial contrast-enhanced T1-weighted MR image shows enhancement within the masslike medulla lesion (arrowhead). This masslike brainstem lesion is a described feature of juvenile-onset Alexander disease.

X连锁肾上腺脑白质营养不良 (X-linked Adrenoleukodystrophy, X-ALD) ▶X-ALD是最常见的过氧化物酶体病,属于X-连锁的隐性遗传,好发人群:3~12岁男童 ▶机制:极长链脂肪酸(VLCFA)分解代谢所需的过氧化物酶体跨膜转运蛋白ABCD1基因(Xq28)突变引起,血清VLCFA水平升高导致神经系统脱髓鞘和肾上腺皮质功能不全 ▶临床表型复杂多样,主要包括脑型(CALD)、肾上腺脊髓神经病(AMN)、单纯肾上腺功能不全等 ▶临床表现:轻度学习障碍或多动症,听力及视力障碍,进展到痴呆和四肢瘫痪 ▶多数有肾上腺功能不全:由ACTH分泌过多引起皮肤色素沉着("古铜色"),小部分患儿可能仅表现出肾上腺症状 ▶实验室:血浆和皮肤成纤维细胞极长链脂肪酸(C26)增高

X-ALD影像表现 ▶双侧对称性白质病变,优先累及顶枕叶白质(约80%),可扩展至颞叶、胼胝体压部,从后向前、从上向下发展 ① 对称性T2高信号:呈"蝴蝶状"分布 ② DWI:弥散受限 ③ 增强:带状或花环样强化,提示活动性炎症 ▶病变呈典型"三带"表现: ✓中央带:坏死、胶质增生所致T2高信号+/-钙化 ✓中间带:边缘强化和弥散受限,提示活动性炎症 ✓外周带:与脱髓鞘区一致的T2高信号,增强无强化 ▶其他:顶枕区、三角区脑白质可有对称性簇状钙化,晚期脑萎缩

X连锁肾上腺脑白质营养不良 (X-ALD)｜Figure 15.X-ALD in a 7-year-old boy with learning difficulty, visual disturbance, nausea, and vomiting. (A) Axial FLAIR MR image shows symmetric confluent periventricular white matter signal intensity abnormality with a posterior predominance and sparing of the subcortical arcuate fibers. The three distinct zones are demonstrated: the central burned-out necrotic core (solid arrow), low-signal-intensity intermediate zone, representing the leading edge of demyelination (arrowhead), and hyperintense outer zone of demyelination without inflammation (dashed arrow). (B-D) Axial diffusion-weighted (B), apparent diffusion coefficient map (C), and contrast-enhanced T1-weighted (D) MR images show the intermediate zone (arrowhead) of enhancement and restricted diffusion.

异染性脑白质营养不良 (Metachromatic Leukodystrophy, MLD)｜MLD是一种常染色体隐性遗传的溶酶体贮积症｜由芳基硫酸酯酶A (ARSA) 基因缺陷引起，导致硫苷脂在中枢和周围神经系统积累，引发脱髓鞘病变｜起病年龄及临床表现分为三型：晚婴型、青少年和成人型｜临床表现：晚婴型最常见、最严重，多于2岁半前起病，早期表现为行走困难、肌张力减低或增高、智力发育障碍，后期出现痉挛型四肢瘫、肌萎缩、癫痫、眼球震颤、视神经萎缩等｜病情常呈进展性，多于5岁前死亡｜Ceramide｜CGT｜Galactocerebroside｜ASA｜CST｜Sulfatide accumulates in lysosomal｜Neuron neuronal dystunction cytokine release｜Astrocyte infiltration cytokine release｜Oligodendrocyte apoptosis broken down by microglia demyelination｜Microglia metabolic stress cytokine release

MLD影像学表现｜Figure 16. MLD in a 6-year-old girl with abnormal gait and strabismus.｜早期大脑半球深部白质融合的对称性T2信号增高，呈蝶翼样分布，中央白质受累为主，早期皮质下弓状纤维（U纤维）保留；晚期可累及弓状纤维｜特征表现："虎斑征"或"豹斑征"(由于白质受累而周围髓鞘保留所致，但不具特异性)｜增强：脑实质病变区缺乏炎性反应，增强后无强化，颅神经和脊神经根可强化｜终末期：病变区白质被胶质细胞增生和瘢痕所代替、出现脑萎缩、皮层下U形纤维减少｜鉴别诊断：需与其他脑白质病X-ALD、亚历山大病等

佩梅病(Pelizaeus-Merzbacher Disease, PMD)｜PMD是一种罕见的X连锁隐性遗传性脑白质营养不良性疾病，发病率约为每10万活产男婴中1.45~1.9人｜机制：由位于X染色体 (xq22) 上的PLP1基因位点异常所引起PMD｜核心：髓鞘形成障碍｜临床特征：多1～5岁起病，预期寿命可达到中年时期｜✓ 典型早期表现：眼球震颤、视神经萎缩、共济失调、发育迟缓（认知和心理运动）｜✓ 进展期：低张力痉挛、认知功能受损、锥体外系表现｜分四型：经典型、先天型、中间型、成人型。经典型多在婴儿期（通常是1岁内）发病，预后最好；先天型临床症状重，通常在婴幼儿期死亡，预后最差

PMD影像表现｜影像学表现：主要特征为髓鞘形成显著延迟或缺失｜髓鞘信号反转，形似新生儿脑改变｜大部分脑白质信号呈未髓鞘化表现｜"豹纹征"：血管周围见髓鞘岛｜半卵圆中心和胼胝体：最明显（近100%受累），锥体束和小脑白质在不同分型受累存在差异｜晚期：进行性脑萎缩

佩梅病 (Pelizaeus-Merzbacher Disease, PMD)｜Figure 17. PMD in a 2-year-old boy with nystagmus, hypotonia, and developmental delay.｜Axial T1-weighted (A) and T2-weighted (B) MR images show minimal myelination (compared with myelination in age-matched control subjects) within the posterior limbs of the internal capsule (solid arrows), optic radiations (dashed arrows), and splenium of the corpus callosum (arrowheads in A), consistent with a hypomyelination disorder. Note that the white matter is slightly hypointense to the gray matter on the T1-weighted image (open arrow in A) and hyperintense to the gray matter on the T2-weighted image (open arrow in B). A PLP1 mutation was confirmed at genetic testing.

线粒体脑肌病伴乳酸酸中毒及卒中样发作 (Mitochondrial Encephalopathy with Lactic Acidosis and Strokelike Episodes, MELAS) ➢MELAS是线粒体脑肌病中最常见的类型，以线粒体基因突变导致的卒中样发作、乳酸酸中毒、脑病和肌病为特征，发病率为1/8500活产儿 ➢80%病例由mtDNA3243A>G点突变（母系遗传），少数由其他mtDNA突变（如3271T>C）或nDNA突变（如POLG基因）引起 ➢发病年龄：2-31岁，以儿童期和青少年期居多 ➢临床表现：特征为卒中样发作（常伴头痛、呕吐、癫痫、偏盲、局灶性神经功能缺损），其他包括身材矮小、感音神经性耳聋、糖尿病、心肌病、血乳酸串升高 ➢可重叠Leigh综合征，少数合并糖尿病、心肌病、肾病及视网膜病等

MELAS影像表现 ➢脑硬死样改变+后部脑区（顶枕叶）多见+跨血管分布的特点 ➢病灶不对称性：单发或多发、散在，以左侧多见，好发于大脑后部顶枕叶为主的皮质及皮质下白质，较少累及基底节、丘脑、小脑、脑干及额叶 ➢病变多变：游走、多变、进行性加重、对称性趋势 ➢特征性MRS：类梗死区和正常脑组织中Lac峰升高，NAA峰减低 ➢ASL：病变区域高灌注（乳酸沉积、微血管扩张） ➢急性期：脑回样肿胀、DWI弥散受限 ➢慢性期、晚期：脑萎缩、软化灶或胶质增生 ➢双侧基底节对称性钙化，最常见苍白球钙化

线粒体脑肌病伴乳酸酸中毒及卒中样发作(MELAS) Figure 18.MELAS in an 11-year-old boy with acute-onset visual disturbance. (A) Drawing illustrates the vascular territories of the brain. The left side of the drawing shows the normal vascular territory of the anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries. The right side of the drawing shows that the area of involvement (red) includes more than one vascular territory. (B) Axial FLAIR MR image shows gyral swelling with associated cortical and subcortical hyperintensity in the left occipital lobe (arrows) that crosses vascular territories (PCA and MCA territories). (C) Single-voxel MR spectroscopy with a time-echo of 135 msec centered on the right basal ganglia shows an inverted peak at 1.3 ppm (arrow) with a doublet morphology, consistent with a lactate (Lac) peak (arrow). Cho = choline, Cr = creatine. Cr2 = second creatine peak.

线粒体脑肌病伴乳酸酸中毒及卒中样发作(MELAS) MELAS, with different disease evolution, in an 11-year-old girl with difficulty swallowing, gagging, dysarthria, bilateral sensorineural hearing loss, and strokelike episodes (a-f) and in a 13-year-old girl with a history of headaches and strokelike symptoms (g, h). (a, b) Axial initial diffusion-weighted (a) and FLAIR (b) MR images in the first patient show a small area of restricted diffusion in the right medial occipital lobe (a) and a larger area of signal intensity abnormalities (b) encompassing two arterial territories, of both the middle and posterior cerebral arteries. In a and b, signal intensity changes are more evident, involving the cortical ribbon. (c) Axial follow-up MR image 4 years later shows that the signal intensity changes in the right cerebral hemisphere are completely resolved. A new focus of signal intensity abnormalities is seen in the left occipital lobe. (d) Subsequent axial follow-up MR image 5 years after the initial study shows complete resolution of the lesion in the left occipital lobe. (e, f) Axial susceptibility weighted MR image (e) and CT image (f) show signs of calcium deposits. (g) Axial initial diffusion-weighted MR image in the second patient shows a large area of restricted diffusion involving the temporal, parietal, and occipital lobes (mainly cortical). (h) Axial follow-up CT image shows that encephalomalacia of the same lesions has developed.