Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Mult Scler Relat Disord. 2018 Feb;20:84-92. doi: 10.1016/j.msard.2018.01.003. Epub 2018 Jan 6.
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.
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.
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.
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%].
Clinical presentations of mitochondrial leukoencephalopathy often mimic an acquired demyelinating disorder. The therapeutic implications of these observations require further exploration.
越来越多的证据表明线粒体功能障碍与多发性硬化等获得性脱髓鞘疾病的发病机制有关。另一方面，一些原发性线粒体疾病，如脑白质病，在 MRI 上显示出神经炎症的证据。由于治疗的意义，需要探讨线粒体疾病和中枢神经系统炎症发作之间的相互关系。
我们旨在分析脑白质病患者的临床病程和 MRI 特征，以确定是否存在任何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。
对 14 例脑白质病患者的临床病程、磁共振成像表现和治疗反应进行了详细分析。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。
本研究共纳入 14 例患者[年龄评估：2-7 岁，男：女=1：1]。基因发现包括 NDUFA1（1）；NDUFV1（4）；NDUFS2（2）；LYRM（2）；MPV17（1）；BOLA3（2）；IBA57（2）的变异。类似于获得性脱髓鞘疾病的临床特征包括伴有脑病的急性局灶性神经功能缺损[14 例中有 10 例，71%]；发热性疾病在前[14 例中有 7 例，50%]；明确的部分或完全激素反应[11 例中有 11 例，100%]；发作性/缓解性复发性神经功能障碍[14 例中有 10 例，71%]；以及随后的稳定而非进行性病程[14 例中有 12 例，85%]。MRI 特征包括弥漫性白质病变[14 例中有 14 例，100%]、弥散受限[14 例中有 11 例，78.5%]、对比增强[13 例中有 13 例，100%]、脊髓受累[13 例中有 8 例，61.5%]、MRS 上的乳酸性峰[13 例中有 13 例，100%]和白质囊肿[14 例中有 13 例，92.8%]。
脑白质病的临床表现常类似于获得性脱髓鞘疾病。这些观察结果的治疗意义需要进一步探讨。
