Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, Okayama, Japan.
Eur J Neurol. 2012 Aug;19(8):1070-8. doi: 10.1111/j.1468-1331.2012.03669.x. Epub 2012 Feb 21.
A variety of hereditary spinocerebellar ataxia (SCA) develops a broad spectrum of both ataxia and non-ataxia symptoms. Cognitive and affective changes are one such non-ataxia symptoms, but have been described only in hereditary SCAs with exonic CAG gene expansion.
We newly found intronic hexanucleotide GGCCTG gene expansion in NOP56 gene as the causative mutation (=SCA36) in nine unrelated Japanese familial SCA originating from Asida river area in the western part of Japan, thus nicknamed Asidan for this mutation. These patients show unique clinical balance of cerebellar ataxia and motor neuron disease (MND), locating on the crossroad of these two diseases. In the nine families, 14 patients were clinically examined and genetically confirmed to Asidan. In the present study, we examined cognitive and affective analyses on 12 patients (seven men and five women) who agreed to join the examination with average age at onset of 53.1 ± 3.2 years, average duration of 12.1 ± 5.2 years, and current average age at 65.1 ± 6.2 years.
The 12 Asidan patients demonstrated a significant decrease in their frontal executive functions measured by frontal assessment battery (FAB) and Montreal cognitive assessment (MoCA) compared with age- and gender-matched controls, whilst mini-mental state examination (MMSE) and Hasegawa dementia score-revised (HDS-R) were within normal range. The decline of frontal executive function was related to their disease duration and scale for the assessment and rating of ataxias (SARA). They also demonstrated mild depression and apathy. Single-photon emission tomography (SPECT) analysis showed that these Asidan patients showed decline of regional cerebral blood flow (rCBF) in a particular areas of cerebral cortices such as Brodmann areas 24 and 44-46.
These data suggest that the patients with Asidan mutation show unique cognitive and affective characteristics different from other hereditary SCAs with exonal CAG expansion or MND.
多种遗传性脊髓小脑共济失调（SCA）表现出广泛的共济失调和非共济失调症状。认知和情感变化就是其中一种非共济失调症状，但仅在具有外显子 CAG 基因扩展的遗传性 SCA 中有所描述。
我们在源自日本西部有田河流域的 9 个无关家族性 SCA 患者中，新发现 NOP56 基因中的内含子六核苷酸 GGCCTG 基因扩展，将其作为致病突变（=SCA36），因此将该突变命名为 Asidan。这些患者表现出独特的小脑共济失调和运动神经元病（MND）的临床平衡，位于这两种疾病的交叉点。在这 9 个家族中，有 14 名患者经过临床检查和基因确认为 Asidan。在本研究中，我们对 12 名同意参加检查的患者（7 名男性和 5 名女性）进行了认知和情感分析，这些患者的平均发病年龄为 53.1±3.2 岁，平均病程为 12.1±5.2 年，当前平均年龄为 65.1±6.2 岁。
12 名 Asidan 患者的额叶执行功能，通过额叶评估量表（FAB）和蒙特利尔认知评估（MoCA）进行测量，与年龄和性别匹配的对照组相比明显下降，而简易精神状态检查（MMSE）和修订后的 Hasegawa 痴呆量表（HDS-R）则在正常范围内。额叶执行功能的下降与他们的疾病持续时间和共济失调评估和评分量表（SARA）有关。他们还表现出轻度抑郁和淡漠。单光子发射计算机断层扫描（SPECT）分析显示，这些 Asidan 患者的大脑皮质特定区域的局部脑血流（rCBF）下降，如 Brodmann 区域 24 和 44-46。
这些数据表明，Asidan 突变患者表现出与具有外显子 CAG 扩展或 MND 的其他遗传性 SCA 不同的独特认知和情感特征。
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