Mitochondrial leukoencephalopathies: A border zone between acquired and inherited white matter disorders in children?
Mitochondrial leukoencephalopathies: A border zone between acquired and inherited white matter disorders in children?
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DOI：
10.1016/j.msard.2018.01.003
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发表时间：
2018-02-01
影响因子：
4
通讯作者：
Taly, Arun B.
中科院分区：
文献类型：
--
作者：
Bindu, Parayil Sankaran;Sonam, Kothari;Taly, Arun B.
背景：越来越多的证据表明，线粒体功能障碍与获得性脱髓鞘疾病（如多发性硬化症）的发病机制有关。另一方面，一些原发性线粒体疾病如线粒体脑白质病在MRI上表现为神经炎症。线粒体疾病和发作性中枢神经系统炎症之间的相互关系需要探索，因为其治疗意义。目的：我们试图分析一组线粒体白质脑病患者的临床病程和MRI特征，以确定是否有类似原发性脱髓鞘疾病的特征。讨论了这些发现的治疗意义。患者与方法：对14例线粒体白质脑病的临床病程、磁共振成像表现及治疗效果进行详细分析。通过临床特征、组织病理学、呼吸链酶测定和外显子组测序确定诊断。结果：纳入14例患者[评估年龄：2-7岁，M: f - 1:1]。遗传结果包括NDUFA1的变异(1)；NDUFV1 (4);NDUFS2 (2);LYRM (2);MPV17 (1);BOLA3 (2);IBA57(2)。与获得性脱髓鞘障碍相似的临床特征包括急性发作伴脑病的局灶性缺陷[10/14,71%]，发病前发热性疾病[7/14,50%]，明确的部分或完全类固醇反应性[11/11]，发作性/复发性缓解性神经功能障碍[10/14,71%]以及随后的稳定而非进行性病程[12/14,85%]。MRI表现为白质融合病变[14/14,100%]，弥散受限[11/14,78.5%]，对比增强[13/ 13100%]，脊髓受累[8/13,61.5%]，MRS乳酸峰[13/13]，白质囊肿[13/14,92.8%]。结论：线粒体白质脑病的临床表现通常与获得性脱髓鞘疾病相似。这些观察结果的治疗意义需要进一步探索。
Background: There is emerging evidence implicating mitochondrial dysfunction in the pathogenesis of acquired demyelinating disorders such as multiple sclerosis. On the other hand, some of the primary mitochondrial disorders such as mitochondrial leukoencephalopathies exhibit evidence of neuroinflammation on MRI. The inter-relationship between mitochondrial disorders and episodic CNS inflammation needs exploration because of the therapeutic implications.Objective: We sought to analyze the clinical course and MRI characteristics in a cohort of patients with mitochondrial leukoencephalopathy to determine features, if any, that mimic primary demyelinating disorders. Therapeutic implications of these findings are discussed.Patients and methods: Detailed analysis of the clinical course, magnetic resonance imaging findings and therapeutic response was performed in 14 patients with mitochondrial leukoencephalopathy. The diagnosis was ascertained by clinical features, histopathology, respiratory chain enzyme assays and exome sequencing.Results: Fourteen patients [Age at evaluation: 2-7 yrs, M: F-1: 1] were included in the study. The genetic findings included variations in NDUFA1 (1); NDUFV1 (4); NDUFS2 (2); LYRM (2); MPV17(1); BOLA3(2); IBA57(2). Clinical Features which mimicked acquired demyelinating disorder included acute onset focal deficits associated with encephalopathy [10/14, 71%], febrile illness preceding the onset [7/14, 50%] unequivocal partial or complete steroid responsiveness [11/11], episodic/relapsing remitting neurological dysfunction [10/14, 71%] and a subsequent stable rather than a progressive course [12/14, 85%]. MRI characteristics included confluent white matter lesions [14/14, 100%], diffusion restriction [11/14,78.5%], contrast enhancement [13/13,100%], spinal cord involvement [8/13,61.5%], lactate peak on MRS [13/13] and white matter cysts [13/14, 92.8%].Conclusion: Clinical presentations of mitochondrial leukoencephalopathy often mimic an acquired demyelinating disorder. The therapeutic implications of these observations require further exploration.