Multipoint linkage analysis of spinocerebellar ataxia and markers on chromosome 6

Heterogeneity among the spinocerebellar ataxias (SCA) has been shown on clinical, biochemical, and genetic criteria. Among the autosomal dominant SCAs, several kindreds have shown loose linkage to the HLA loci on chromosome 6, while linkage in other kindreds has been rejected. The advent of multipoint linkage analysis allows the use of several marker loci simultaneously, thus increasing the amount of usable information. We have reanalyzed linkage data from a large kindred with SCA and provide evidence for a telomeric location of the SCA gene in this family. Knowledge of the relative gene location will ease the identification of the SCA gene by reducing the size of the chromosomal regions that must be examined.     

多系统萎缩11例临床分析

目的 探讨多系统萎缩的临床和发病特点。方法 结合文献复习,分析了１１例多系数萎缩的临床表现,包括橄槛桥小脑萎缩８例;纹状体黑质变性２例;特发性体位性低血压１例。．结果 本组资料显示：三种疾病均为中年发病,大多为慢必起病进行加重,平均病程在４年左右。结论 随着现代化诊断仪器的普及,对本病的诊断水平有所提高,但尚缺乏的治疗手段。     

橄榄体桥脑小脑萎缩的MRI诊断

目的探讨OPCA的MRI的诊断价值。方法回顾总结22例OPCA典型的MRI表现。结果22例病例橄榄体桥脑、小脑半球及蚓部明显萎缩。周围脑室、脑池、脑沟明显扩大。11例桥脑下份“十字交叉”形长T2信号。4例小脑中脚长T2信号。3例合并轻度脑萎缩。结论OPCA的MRI表现具有特征性,能作出正确诊断。     

Abnormalities of mitochondrial enzymes in hereditary ataxias

The activity of 7 mitochondrial enzymes, fumarase, NAD-malate dehydrogenase (MDH), citrate synthase (CS), valine dehydrogenase (VDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), pyruvate dehydrogenase complex (PDHC) has been measured in platelet preparations from patients affected by Friedreich's ataxia (FA), dominant and non-dominant olivopontocerebellar atrophy (DOPCA, NDOPCA) and normal individuals. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05) and SDH (P less than 0.05) activities were observed in FA patients. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05), SDH (P less than 0.05) and CS (P less than 0.05) activities were Observed in ND-OPCA patients, whereas in DOPCA patients only GDH activity was significantly (P less than 0.05) decreased. In 8 of 10 patients with FA and in all patients with NDOPCA the activity of one or more of 4 enzymes, i.e. GDH, VDH, SDH, PDHC, was lower than the lowest of control values. Four of 6 patients with DOPCA had GDH activity lower than the lowest of control values. These results indicate that abnormalities of mitochondrial metabolism is a constant element in hereditary ataxia and suggest that the alteration primary leading to the different types of ataxias should be related to mitochondrial oxidative metabolism, at least at a regulatory level.     

MRI测量诊断橄榄-桥脑-小脑萎缩

目的：通过MRI测量正常成人及OPCA患的脑干及周围间隙，探讨其在诊断OPCA中的价值。方法：正常成人106例和OPCA患21例，采用正中矢状面T1W图像直接光标测量计算。结果：以绝对值测量时OPCA患脑干各径线值均小于正常组；桥脑与桥前池比值（B／F），延髓与延髓前池比值（C／G）在判断脑干的正常形态及异常改变中意义较大。结论：MRI测量可以为诊断OPCA提供较为客观和准确的参考价值。     

HLA-linked spinocerebellar ataxia: a clinical and genetic study of large Italian kindreds

Five families with late onset autosomal dominant spinocerebellar ataxia, were studied. Linkage between the disease and HLA loci on the short arm of chromosome 6 was shown in the two largest pedigrees. Clinical study of 26 patients and neuropathological study in one are reported. The disease was characterized by cerebellar and pyramidal involvement variably associated with cranial nerve and peripheral nervous system disorders. A remarkable concordance of the main clinical features was observed in patients with similar disease duration. Comparison with previous reports of HLA-linked spinocerebellar ataxia kindreds showed differences in clinical phenotypes. Although these might be due to genetic variation, the hypothesis is suggested that the phenotype might appear more homogeneous if disease duration is taken into account.     

橄榄桥脑小脑萎缩的临床观察及随访研究

目的 :探讨橄榄桥脑小脑萎缩 (OPCA)患者病情的发生、发展和转归的规律及可能影响因素。方法 :对确诊的 38例 (家族性 2例 ,散发性 36例 )进行脑脊液、头颈 CT、 MRI检查及临床特点分析 ,并对其中 2 8例进行了 1～ 12年随访。结果 :1SOPCA和 FOPCA平均发病年龄分别为 4 6 .9岁和 2 0岁 ;平均病程分别为 6 .7年和 14 .5年。 2受累系统症状出现频率为小脑共济失调 92 .1% ,锥体束征 86 .8% ,构音障碍 84 .2 % ,自主神经损害 76 .3%。 3病程第一年内头颅 CT和 MRI分别有 16 .7%和 70 %的异常。 4平均确诊时间为 4 .1年 ,目前治疗无法改变其转归 ,随访 2 8例死亡 3例 ,死因分别为吸入性肺炎、窒息及全身衰竭。结论 :OPCA受累系统以小脑最多 ,无遗传家族史者病情发展较快 ,多死于并发症。核磁共振为首选辅助检查 ;随访有助于早期确诊。     

橄榄桥脑小脑萎缩51例临床分析

目的：分析橄榄桥脑小脑萎缩（OPCA）的临床表现、CT及MRI特征,以利早期诊断。方法：对51例OPCA病人的临床表现及其18头颅CT和33例头颅MRI特征进行回顾性分析。结果：OPCA男性多于女性,平均年龄45．5岁,平均病程12年,其临床表现多种多样,以小脑症状,植物神经症状及锥体外系症状多见,头颅MRI比头颅CT效果好,以小脑和干萎缩为主,大脑皮质萎缩轻,结论,成年人出现小脑性共济失调,植物神经功能紊乱和锥体外系症状,应高度怀疑OPCA,且MRI有助于早期诊断。     

橄榄脑桥小脑萎缩患者椎-基底动脉MRA改变

目的：应用3.0TMR与MRA探讨橄榄脑桥小脑萎缩（OPCA）患者椎-基底动脉的改变。方法：OPCA患者27例、健康志愿者50例,分别接受常规M R及MRA检查,MRA图像观察以最大密度投影重组后图像为主,观察椎-基底动脉病变类型。对所有资料进行统计学分析。结果：27例患者均有椎动脉M RA异常,其中椎-基底动脉管腔变细6例,迂曲4例,狭窄15例,闭塞3例。OPCA患者椎动脉改变与正常人比有显著差异。结论：OPCA患者椎-基底动脉系统血管异常,血供减少,这可能是导致其发病的原因,或者是重要的中间环节,此可为针对性治疗提供重要依据。     

Dominant Spinocerebellar Ataxia: Genetic Counseling

Dominantly inherited spinocerebellar ataxia (OPCA 1) poses a particular problem for genetic counseling due to late age of onset. Liability for disease using observed age of onset can be combined with HLA linkage data to provide revised estimates of risk for affection. Where data is informative, certain combinations may yield estimates which improve so rapidly with age that postponement of childbearing may become a strong consideration as an option.