Gambardella A, Annesi G, Bono F, Spadafora P, Valentino P, Pasqua A A, Mazzei R, Montesanti R, Conforti F L, Oliveri R L, Zappia M, Aguglia U, Quattrone A
Institute of Neurology, School of Medicine of Catanzaro, Italy.
J Neurol. 1998 Oct;245(10):647-52. doi: 10.1007/s004150050261.
We report on the clinical, neuropsychological, neurophysiological, computerized eye movement, magnetic resonance imaging (MRI) and molecular findings from 17 individuals affected with spinocerebellar ataxia type 2 (SCA2) belonging to three families. The average age at onset of the symptoms was 35.6, 11.9 (mean, SD) years. The mean age at onset of the symptoms in the parents was 44.8, 8.2 years, and in the offspring it was 28.7, 7.2 years. In 12 parent-child pairs, the mean anticipation was -15.75, 9.1 years (range -8.1 to -23.3 years, t = -4.9, P = < 0.002). The mutated SCA2 alleles ranged from 38 to 42 CAG repeats, while the normal alleles ranged from 22 to 24 repeats, with 97% of the alleles having 22 repeats. Small differences in the number of CAG repeats influenced the age at onset and rate of progression of the disease considerably. Indeed, patients presenting with their first symptom at an age of 35 years or later with a slower course of the disease harboured between 38 and 39 repeats. In contrast, patients carrying > or = 40 CAG repeats manifested the disease prior to 30 years of age and had a faster disease progression toward incapacity. The presenting symptom was always gait ataxia. Slow saccades occured from the beginning of the disease despite normal delay, accuracy and smooth pursuit eye movements. The neuropsychological study showed early and selective impairment of conceptual reasoning ability, as detected by the Wisconsin Card Sorting Test (WCST). It is noteworthy that a significant mutual relationship was observed between performance on the WCST and saccade velocity. All of these findings favour the hypothesis that the disease process of SCA2 in regions other than the cerebellum and brain stem affects severely and early those cortical structures involved in the control of both visually guided saccades and WCST performance.
我们报告了来自三个家族的17例2型脊髓小脑共济失调（SCA2）患者的临床、神经心理学、神经生理学、计算机化眼动、磁共振成像（MRI）及分子学研究结果。症状出现的平均年龄为35.6±11.9岁（均值，标准差）。父母出现症状的平均年龄为44.8±8.2岁，后代为28.7±7.2岁。在12对亲子中，平均遗传早现现象为-15.75±9.1岁（范围-8.1至-23.3岁，t=-4.9，P<0.002）。突变的SCA2等位基因的CAG重复次数在38至42次之间，而正常等位基因的CAG重复次数在22至24次之间，97%的等位基因有22次重复。CAG重复次数的微小差异对疾病的发病年龄和进展速度有显著影响。实际上，在35岁及以后出现首个症状且病程较慢的患者，其CAG重复次数在38至39次之间。相比之下，携带≥40次CAG重复的患者在30岁之前出现疾病，且疾病向失能进展的速度更快。首发症状始终为步态共济失调。尽管延迟、准确性和跟踪眼动正常，但从疾病一开始就出现缓慢扫视。神经心理学研究显示，通过威斯康星卡片分类测验（WCST）检测，概念推理能力早期出现选择性损害。值得注意的是，WCST表现与扫视速度之间存在显著的相互关系。所有这些发现都支持这样一种假说，即SCA2在小脑和脑干以外区域的疾病进程会严重且早期影响那些参与视觉引导扫视控制和WCST表现的皮质结构。
