OBJECTIVE: Diagnosis of sporadic cerebellar ataxia is a challenge for neurologists. A wide range of potential causes exist, including chronic alcohol use, multiple system atrophy of cerebellar type (MSA-C), and sporadic late cortical cerebellar atrophy. Recently, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was identified in a cohort of patients with non-MSA-C sporadic cerebellar ataxia. The aim of this study is to genetically screen genes involved in SCA in a Japanese single-hospital cohort. METHODS: Over an 8-year period, 140 patients with cerebellar ataxia were observed. There were 109 patients with sporadic cerebellar ataxia (no family history for at least four generations, 73 patients with MSA-C, and 36 patients with non-MSA-C sporadic cerebellar ataxia) and 31 patients with familial cerebellar ataxia. We performed gene analysis comprising SCA1, 2, 3, 6, 7, 8, 12, 17, 31, and dentatorubro-pallidoluysian atrophy (DRPLA) in 28 of 31 non-MSA-C sporadic patients who requested the test. Familial patients served as a control. RESULTS: Gene abnormalities were found in 57% of non-MSA-C sporadic cerebellar ataxia cases. Among patients with sporadic cerebellar ataxia, abnormalities in SCA6 were the most common (36%), followed by abnormalities in SCA1 (7.1%), SCA2 (3.6%), SCA3 (3.6%), SCA8 (3.6%), and DRPLA (3.6%). In contrast, gene abnormalities were found in 75% of familial cerebellar ataxia cases, with abnormalities in SCA6 being the most common (29%). For sporadic versus familial cases for those with SCA6 abnormalities, the age of onset was older (69 years vs. 59 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively) in the former than in the latter (not statistically significant). CONCLUSION: Autosomal-dominant mutations in SCA genes, particularly in SCA6, are not rare in sporadic cerebellar ataxia. The reason for the frequency of mutations in SCA6 remains unclear; however, the reason may reflect a higher age at onset and variable penetrance of SCA6 mutations.
Age of Onset ; Asian Continental Ancestry Group* ; Atrophy ; Cerebellar Ataxia ; Cohort Studies* ; Diagnosis ; Family Characteristics ; Genetic Testing* ; Heredity ; Humans ; Multiple System Atrophy ; Penetrance ; Spinocerebellar Ataxias*

Most patients on hemodialysis (HD) have left ventricular (LV) remodeling as a result of pressure and volume overload, which may lead to hypertrophy (LVH) and dilation, resulting in heart failure (HF). LV torsion by the inner and outer oblique myocardial bands may contribute in part to the ejection fraction (EF). LV dilation is associated with reduction of torsion. We assessed the hypothesis that LV dilation and decreased torsion at the sub-epicardium assessed by 3-dimensional speckle tracking echocardiography (3D-STE) may cause reduced LVEF in patients on HD. LV volume, strain, and torsion at the sub-endocardium and sub-epicardium were examined using 3D-STE in 76 patients on HD (age 64 ± 2 years) and 22 controls (age 71 ± 9 years). The HD patients were divided into 2 subgroups according to LV size (17 HD with LV end diastolic volume ≥ 70 and 59 HD with volume ＜ 70 mL/m2). Torsion (°/cm) is defined as the difference in the rotation angle between base and apex divided by the length of the LV long axis. LVEF, strain, and torsion at both layers in all HD patients (n = 76) were comparable to those in the controls (torsion at the sub-endocardium: 2.2 ± 0.7 vs 2.4 ± 1.1°/cm) despite increased LV mass and volume. In HD with dilation, LV volume increased and LVEF reduced compared to HD without dilation (LVEF: 63 ± 7, 64 ± 6, 57 ± 9％), with decreased longitudinal strain and torsion at both layers (torsion at sub-epicardium: 1.4 ± 0.7, 1.6 ± 1.0, 1.1 ± 0.6°/cm). There was no significant difference in circumferential strain at the sub-epicardium among the 3 groups. There was some correlation between torsion and EF (r = 0.34, p ＜ 0.01) and end diastolic volume (r = －0.36, p ＜ 0.01). LVEF and torsion at the sub-endocardium and sub-epicardium were reduced in HD with LV dilation, suggesting that volume control is important in HD to prevent HF with reduced EF because of reduced LVEF by LV dilation and oblique myocardial fiber damage at the sub-epicardium.