Higgins J J, Harvey-White J D, Nee L E, Colli M J, Grossi T A, Kopin I J
Clinical Neurogenetics Unit, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurol Neurosurg Psychiatry. 1996 Dec;61(6):591-5. doi: 10.1136/jnnp.61.6.591.
To serially assess changes in lumbar CSF biogenic amines, radiographic characteristics, and neurological signs in 34 patients with dominantly inherited ataxia.
Mutational analysis was used to identify genetic subgroups. Annual assessment of lumbar CSF monoamine metabolites using a gas chromatographic/mass spectrometric method and morphometric measurements of the cerebellum, pons, and the cervical spinal cord on MRI were analysed for each patient and compared with normal controls.
Patients with CAG trinucleotide repeat expansions on chromosome 6p (mutSCA1) and chromosome 14q (mutSCA3) had only about one half the normal concentrations of lumbar CSF homovanillic acid (HVA) whereas, 5-hydroxyindoleacetic acid (5-HIAA) concentrations were similar to those in age matched normal subjects. The HVA and 5-HIAA concentrations in clinically similar patients without mutSCA1 or mutSCA3 were normal. One year after the first study, HVA concentrations were reduced by a mean of 22% regardless of the patient's SCA mutation. Abnormalities on MRI were consistent with a spinopontine atrophy in patients with mutSCA3, spinopontocerebellar atrophy in patients with mutSCA1, and "pure" cerebellar atrophy in patients without these mutations.
Quantitative MRI measurements were not useful in monitoring progression of disease but lumbar CSF HVA concentrations and total scores on a revised version of the ataxia clinical rating scale seemed to progress in parallel.
对34例常染色体显性遗传性共济失调患者的腰椎脑脊液生物胺、影像学特征和神经体征进行系列评估。
采用突变分析确定基因亚组。每年使用气相色谱/质谱法对每位患者的腰椎脑脊液单胺代谢产物进行评估，并对MRI上小脑、脑桥和颈髓进行形态测量，与正常对照组进行比较。
6号染色体短臂（mutSCA1）和14号染色体长臂（mutSCA3）存在CAG三核苷酸重复扩增的患者，其腰椎脑脊液高香草酸（HVA）浓度仅约为正常浓度的一半，而5-羟吲哚乙酸（5-HIAA）浓度与年龄匹配的正常受试者相似。无mutSCA1或mutSCA3的临床症状相似患者的HVA和5-HIAA浓度正常。首次研究一年后，无论患者的脊髓小脑共济失调（SCA）突变情况如何，HVA浓度平均降低22%。MRI异常表现为：mutSCA3患者为脊髓脑桥萎缩，mutSCA1患者为脊髓脑桥小脑萎缩，无这些突变的患者为“单纯”小脑萎缩。
定量MRI测量对监测疾病进展无用，但腰椎脑脊液HVA浓度和修订版共济失调临床评定量表的总分似乎呈平行进展。
