Genetic Screening for Spinocerebellar Ataxia Genes in a Japanese Single-Hospital Cohort

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.

Usefulness of CEA and CA19-9 for detecting a previously undiagnosed cancer in patients with acute ischemic stroke

Background: Ischemic stroke can occur in patients with an underlying or undiagnosed malignancy. We aim to report the clinical features of ischemic stroke patients in whom a previously undiagnosed cancer was detected after stroke onset. Methods: Clinical and laboratory records of 28 consecutive ischemic stroke patients with cancer were reviewed retrospectively. The analysis was made focused on the differences between patients who were already diagnosed as having cancer before ischemic stroke (Group A) and those in whom a previously undiagnosed cancer was detected after ischemic stroke onset (Group B). Results: There were 18 patients in the Group A and 10 in the Group B. In Group B patients, the indicators that led to the detection of cancer were as follows: ascites (n=2), liver enzyme elevation (n=2), anemia (n=2), hematemesis (n=1), hematochezia (n=1), and sore throat (n=1), and autopsy (n=1). Nine of the 10 patients (90%) in Group B, and 6 of the 18 (33%) in Group A had a gastrointestinal cancer. In Group B, 8 of the 9 patients showed elevated serum carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9). Stroke relapse, prognosis, diffusion-weighted imaging patterns and laboratory fi ndings were not different between the 2 groups. Conclusions: Gastrointestinal cancer was frequent in ischemic stroke patients with newly diagnosed malignancy after stroke onset in this study among Japanese patients. Physicians should be aware that underlying cancer may be present particularly in ischemic stroke patients whose stroke etiology is unclear or who have anemia or liver dysfunction. In such cases, measurements of CEA and CA19-9 levels are easy and useful screening for the detection of occult malignancies.