Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes
Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes
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DOI：
10.1093/brain/awq067
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发表时间：
2010-05-01
期刊：
影响因子：
14.5
通讯作者：
Bindoff, Laurence A.
中科院分区：
文献类型：
--
作者：
Tzoulis, Charalampos;Neckelmann, Gesche;Bindoff, Laurence A.
线粒体DNA聚合酶γ的催化亚基的突变引起广泛的临床疾病，从婴儿肝性脑病到青少年/成人发作的脊髓小脑性共济失调和迟发性进行性眼外肌麻痹。这些综合征中有几种与脑病有关，其特征性表现为神经系统快速恶化和急性脑损伤的发展。本研究的目的是研究聚合酶γ相关脑病中中枢神经系统病变的性质、分布和自然演变，特别关注通过磁共振成像识别的病变。我们比较了放射学、电生理学和病理学结果，以研究急性发作和急性脑损伤的潜在机制。我们共研究了32例聚合酶γ-脑病患者的112例磁共振断层扫描和11例计算机断层扫描，包括在疾病的慢性和急性期进行的多项系列检查，在一些情况下，磁共振波谱和系列弥散加权研究。比较影像学、脑电图和尸检的数据，以研究潜在的疾病过程。我们的研究结果表明，磁共振成像在聚合酶γ相关性脑病中具有高灵敏度，并能识别出个体综合征的特异性模式。一种与c.1399G > A和c.2243G > C突变相关的慢性聚合酶γ-脑病形式的特征在于进行性大脑和小脑萎缩以及丘脑、小脑深部结构和延髓的局灶性病变。急性脑病，无论是婴儿期还是晚发型，在急性发作时都表现出类似的皮质卒中样病变。这些病变可以发生在有或没有并发癫痫活动的脑电图证据的情况下，并且具有强烈提示神经元能量衰竭的扩散、光谱和组织学特征。因此，我们认为婴儿期和晚发型聚合酶γ相关脑病是一个连续体的一部分。
Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging. We compared radiological, electrophysiological and pathological findings where available to study potential mechanisms underlying the episodes of exacerbation and acute cerebral lesions. We studied a total of 112 magnetic resonance tomographies and 11 computed tomographies in 32 patients with polymerase gamma-encephalopathy, including multiple serial examinations performed during both the chronic and acute phases of the disease and, in several cases, magnetic resonance spectroscopy and serial diffusion weighted studies. Data from imaging, electroencephalography and post-mortem examination were compared in order to study the underlying disease process. Our findings show that magnetic resonance imaging in polymerase gamma-related encephalopathies has high sensitivity and can identify patterns that are specific for individual syndromes. One form of chronic polymerase gamma-encephalopathy, that is associated with the c.1399G > A and c.2243G > C mutations, is characterized by progressive cerebral and cerebellar atrophy and focal lesions of the thalamus, deep cerebellar structures and medulla oblongata. Acute encephalopathies, both infantile and later onset, show similar pictures with cortical stroke-like lesions occurring during episodes of exacerbation. These lesions can occur both with and without electroencephalographic evidence of concurrent epileptic activity, and have diffusion, spectroscopic and histological profiles strongly suggestive of neuronal energy failure. We suggest therefore that both infantile and later onset polymerase gamma related encephalopathies are part of a continuum.