Progressive cavitating leukoencephalopathy: A novel childhood disease
Progressive cavitating leukoencephalopathy: A novel childhood disease
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DOI：
10.1002/ana.20671
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发表时间：
2005-12-01
影响因子：
11.2
通讯作者：
DiMauro, S
中科院分区：
文献类型：
--
作者：
Naidu, S;Bibat, G;DiMauro, S
我们报告了19例先前未描述的神经退行性综合征患者，其特征是在2个月至3.5岁之间出现急性发作的应激性或神经功能障碍，随后出现稳定或间歇性的临床恶化。7名儿童在11个月至14岁之间死亡。头颅磁共振成像(MRI)显示，病变活跃的区域有斑片状白质脑病，伴有空洞和血管通透性。早期病变累及胼胝体和半卵圆中心，有或无小脑或脊髓受累。反复发作后，组织丢失的区域与较老的病变结合在一起，成为大脑或脊髓中更大的囊性区域。随之而来的是弥漫性痉挛、痴呆症、植物状态或死亡。直到课程后期，灰色物质才得以幸免。在某些情况下，不完全的临床或MRI恢复发生在发作后。临床病程从快速恶化到长期稳定，这是临床或MRI变化无法预测的。脑、血和脑脊液中乳酸水平升高，尿有机酸异常，肌肉呼吸链酶变化存在，但不一致，没有可识别的线粒体DNA突变或缺失。病理检查显示髓鞘少的U纤维严重丢失，轴突断裂，无炎症的空洞性病变。家族性发生和血缘关系提示这一独特实体的常染色体隐性遗传。
We report 19 patients with a previously undelineated neurodegenerative syndrome characterized by episodic acute onset of irritability or neurological deficits between 2 months and 3.5 years of age, followed by steady or intermittent clinical deterioration. Seven children died between 11 months and 14 years of age. Cranial magnetic resonance imaging (MRI) shows patchy leukoencephalopathy with cavities, and vascular permeability, in actively affected regions. Early lesions affect corpus callosum and centrum semiovale, with or without cerebellar or cord involvement. After repeated episodes, areas of tissue loss coalesce with older lesions to become larger cystic regions in brain or spinal cord. Diffuse spasticity, dementia, vegetative state, or death ensues. Gray matter is spared until late in the course. In some, incomplete clinical or MRI recovery occurs after episodes. The clinical course varies from rapid deterioration to prolonged periods of stability that are unpredictable by clinical or MRI changes. Elevated levels of lactate in brain, blood, and cerebrospinal fluid, abnormal urine organic acids, and changes in muscle respiratory chain enzymes are present but inconsistent, without identifiable mitochondrial DNA mutations or deletions. Pathological studies show severe loss of myelin sparing U-fibers, axonal disruption, and cavitary lesions without inflammation. Familial occurrence and consanguinity suggest autosomal recessive inheritance of this distinct entity.