Pontine spongy degeneration of white matter associated with hepatic encephalopathy

Spongy degeneration of white matter localized to basis pontis was found in a 47-year-old woman with hepatic encephalopathy. In this clinical setting, the lesion resembled those changes described by Victor et al and found primarily in cerebral cortex, subcortical white matter, and putamen. Isolated involvement of the basis pontis and ventral midline tegmentum of pons has not, to our knowledge, been previously reported. The morphologic appearance and distribution distinguish this lesion from central pontine myelinolysis. The possible vascular cause of this localized interstitial edema is discussed.     

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome)

We describe 14 patients, from 11 families, who have a progressive encephalopathy with early onset. The clinical signs of the disease are severe hypotonia, convulsions with hypsarrhythmia, profound mental retardation, hyperrcflexia, transient or persistent edema, and optic atrophy. These findings and the characteristic dysmorphic features allow recognition of these patients, although no basic metabolic defect has been found. Microcephaly and atrophy of the brain develop, especially in the cerebellar and brain stem areas. An autosomal recessive mode of inheritance is likely.     

Neurometrics in cerebral ischemia and uremic encephalopathy

The neurometric method as introduced by John was used to study three groups of patients with cerebral ischemia, three groups of patients with renal disease and an additional normal control group. The traditional neurometric approach was slightly modified: relative band power values were not expressed as a percentage of the total power per derivation but as a percentage of the "global power"; frequency matrices were used in addition to power matrices. From the study of the three groups of patients with one-sided supratentorial ischemia it appeared that sensitivity and specificity are completely satisfactory when using neurometrics in patients with severe ischemia in the middle cerebral artery territory studied within 48 hours of the onset of the stroke. However, in ischemia patients with less pronounced clinical signs and especially in patients without persistent neurological deficit the sensitivity is much lower. In studying dialysed and non-dialysed renal patients signs of an (often subclinical) encephalopathy could be detected in approximately 37% of all patients. Follow-up studies of the ischemia patients and the renal patients over a period of several years revealed a parallelism between clinical scores and qEEG scores in the ischemia patients; almost all qEEG improvement occurred in the first three months after the stroke. The qEEG profile of the groups of dialysed patients tended to be more or less stable over a period of several years.     

Biallelic variants in WARS2 encoding mitochondrial tryptophanyl‐tRNA synthase in six individuals with mitochondrial encephalopathy

Mitochondrial protein synthesis involves an intricate interplay between mitochondrial DNA encoded RNAs and nuclear DNA encoded proteins, such as ribosomal proteins and aminoacyl‐tRNA synthases. Eukaryotic cells contain 17 mitochondria‐specific aminoacyl‐tRNA synthases. WARS2 encodes mitochondrial tryptophanyl‐tRNA synthase (mtTrpRS), a homodimeric class Ic enzyme (mitochondrial tryptophan‐tRNA ligase; EC 6.1.1.2). Here, we report six individuals from five families presenting with either severe neonatal onset lactic acidosis, encephalomyopathy and early death or a later onset, more attenuated course of disease with predominating intellectual disability. Respiratory chain enzymes were usually normal in muscle and fibroblasts, while a severe combined respiratory chain deficiency was found in the liver of a severely affected individual. Exome sequencing revealed rare biallelic variants in WARS2 in all affected individuals. An increase of uncharged mitochondrial tRNA^Trp and a decrease of mtTrpRS protein content were found in fibroblasts of affected individuals. We hereby define the clinical, neuroradiological, and metabolic phenotype of WARS2 defects. This confidently implicates that mutations in WARS2 cause mitochondrial disease with a broad spectrum of clinical presentation.     

HIE幼龄大鼠神经元自噬诱导线粒体功能障碍的研究

目的:探讨细胞自噬对缺氧缺血性脑病(HIE)幼龄大鼠神经元线粒体功能的影响。方法:随机选取10日龄SPF级SD大鼠30只,分为假手术(sham)组和HIE组,后者结扎单侧颈总动脉复制缺血缺氧模型。取脑组织行镜下病理观察,免疫组化分析活化型caspase-3和LC3B-II蛋白表达;体外实验中观察缺氧诱导的原代大鼠神经元的自噬过程,Western blot检测相关蛋白,并对大鼠神经元线粒体功能进行测试。结果:(1)与sham组相比,HIE组大鼠出现脑萎缩和脑室增宽;HIE组免疫组化显示活化型caspase-3和LC3B-II蛋白表达上调(P<0.01);(2)体外细胞实验发现,缺氧可诱导大鼠神经元出现自噬和凋亡;(3)与sham组相比,单纯缺氧的神经元内活性氧簇增加,线粒体超氧化物上调,线粒体跨膜电位降低(P<0.01)。结论:在HIE大鼠模型中,缺氧诱导的神经元线粒体功能障碍,可能与缺氧时神经元出现的自噬和凋亡有关。这一结果将为临床上开发细胞自噬因子类药物治疗HIE提供了新的思路。     

Progressive spinal cord compression and degeneration of nerve fibers in rats

目的:探讨在进行性压迫性脊髓损伤过程中白质纤维溃变的规律.方法:采用自行设计的压迫装置制作进行性压迫性脊髓损伤模型.运用H-E、Luxol fast blue (LFB)、透射电镜和免疫荧光等方法,分别于压迫后1、3、7d观察脊髓白质纤维变化.结果:脊髓受压1d后,白质髓鞘化神经纤维出现水肿,排列疏松、髓鞘缺失等退行性溃变;随着压迫时间延长,神经纤维溃变加重,纤维数目逐渐减少,与对照组和正常组比较差异有统计学意义.髓鞘碱性蛋白阳性神经纤维变性,数量减少.结论:进行性压迫性脊髓损伤可诱发神经纤维脱髓鞘病变,并随着压迫时间推移溃变逐渐加重.     

Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice

Huntington's disease (HD) and spinocerebellar ataxia type 7 (SCA7) belong to a group of progressive neurodegenerative diseases caused by polyglutamine (polyQ) expansions. SCA7 is the only one to display degeneration in the retina, a tissue usually spared in HD. We previously described a SCA7 transgenic retinal model expressing mutant full length ataxin-7 in rod photoreceptors. These mice develop a severe and characteristic retinopathy. We show here that R6 transgenic mice, which reproduce many features of HD, express mutant huntingtin in the retina leading to strong vision deficiencies and retinal dystrophy. These two different polyQ mouse models exhibit comparable early and progressive retinal degeneration and dysfunction. These abnormalities are reminiscent of other retinal degeneration phenotypes (in particular rd7/rd7 mice) where photoreceptor cell loss occurs. Retinopathy in R6 and R7E models can be monitored in living mice by ERG and fundus examination, which can facilitate in vivo evaluation of therapeutic agents in polyQ disorders.     

脑血管病的脑电地形图研究

采用脑电地形图（ＢＥＡＭ）对６３例脑血管病病人脑电活动进行了研究。一组正常人（ｎ＝３３）脑电地形图与之对比，做出显著概率差异地形图，当Ｚ值≥２．００时判为异常。结果表明：ＢＥＡＭ在发现脑血管病病人脑电活动异常及病灶定侧定位方面，较脑电图（ＥＥＧ）目测分析敏感准确；轻微脑缺血病人（ＴＩＡ、ＲＩＮＤ）ＢＥＡＭ的异常明显率高于ＣＴ；在ＢＥＡＭ各频域指标中，以δ、θ、δ＋θ／α＋β为佳；可作为脑血管病病人的病灶定侧定位的一项独立指标。     

Causality of parenchymal and vascular changes in rats with experimental thiamine deficiency encephalopathy

The causality of vascular and parenchymal damage to the central nervous system (CNS) was examined In rats with thiamine deficiency. Male Sprague Dawley rats were divided Into two groups; one was given a thiamlne-deficient diet ODD) and Injected Intraperitoneally with 10μg/100g bodyweight pyrithlamine (PT) In order to analyze morpho-metrically the topographical and sequential relationship between vascular and parenchymal changes and vase dilatation, and the other was given a TDD and 50 μg/100 g bodyweight PT in order to determine hemorrhagic sites using serial dons. Histological examination showed that sponglotic change occurred selectively in the Interior colllculus (100%) from day 19, and thereafter In the thalamus (95%), mammlllary body (50%) and nuclei olivaris and vestlbularls of the pons (25%), with or without hemorrhage. Simultaneously, glycogen accumulation was also observed In these regions at a frequency similar to that of hemorrhage. Ultrastructurally, however, hydroplc swelling of astrocytic and neuronal processes without glycogen accumulation was observed as early as day 9 In the inferior cofliculus, at which time an Increase of glial fibrillary acldic protein-positive processes was also recognized. The Superior colllculus was completely spared. From day 22 vasodilatation of the Inferior colliculus occurred, concomltantly with bodyweight loss and neurological symptoms. Twenty-two examined hemorrhages, which occurred in the thalamus and Inferior colliculus, were distributed along the arterioles or capillarles on the arterial side. In conclusion, the morphological CNS changes caused by thiamine deficiency with administration of low-dose PT in rats begin as hydropic swelling of neuronal and astrocytic processes, followed by hemorrhage and, thereafter, by vasodllatatlon. The predilectlon for hemorrhage on the arterial side without parenchymal changes suggests that petechial hemorrhage Is not simply secondary to parenchymal changes, but Is due to hemadynamlc change resulting from thlamfne deficiency-Induced vascular dysfunction.     

Progressive morphometric and cognitive changes in vascular dementia.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.     

线粒体功能障碍在椎间盘退变中的作用

线粒体是调节细胞功能和生存的多种细胞内信号通路的重要参与者,在年龄相关的退行性疾病中扮演了至关重要的角色.椎间盘退变是一种年龄相关的退行性疾病,以细胞外基质降解加速、细胞丢失和炎症反应为特征.近年来,大量体内外研究报道称,线粒体功能障碍通过影响多种病理生理过程,包括氧化应激、炎症小体激活、线粒体自噬、细胞衰老、细胞死亡...     

肾上腺髓质素与脑血管病

肾上腺髓质素 (Adrenomedullin ,AM )是一种新发现的生物活性肽 ,在人体多种组织中都有AMmRNA的表达。AM具有扩张血管、降低血压、排尿利钠、抑制内皮细胞凋亡、影响内分泌的功能。在脑血管病的发生发展中起重要的保护作用。     

Spinocerebellar degeneration and cerebral hypomyelination in a family

The proband is a 24-year-old woman who developed symptoms of a spinocerebellar degeneration in early childhood. Neurological examination revealed normal cognitive function, optic atrophy, dysarthria, titubation, action tremors, increased deep tendon reflexes, Babinski's signs, and a spastic scissoring gait. The magnetic resonance imaging (MRI) showed an abnormal increased signal on long TR images involving white matter throughout the cerebral hemispheres, most striking in the subcortical white matter, and to a lesser degree in the brainstem, compatible with diffuse hypomyelinating or dysmyelinating diseases. Metabolic and chromosomal studies were normal. Her 49-year-old mother developed similar symptoms in her 20s and is now wheelchair-bound. Findings on neurological examination and MRI were similar to her daughter but more severe. The proband's maternal grandfather had a female cousin who had a neurological illness beginning in her 20s with similar symptoms and signs and died at the age of 44 years. Spinocerebellar degenerations are a group of syndromes with similar clinical manifestations but heterogeneous etiology. We report a family with spinocerebellar degeneration with distinct MRI findings compatible with hypomyelination or dysmyelination which has not heretofore been described. This family may represent a new spinocerebellar syndrome due to an abnormality of as yet an undetermined gene. © 1995 Wiley-Liss, Inc.