Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA)

In order to identify new metabolic abnormalities in patients with complex neurodegenerative disorders of unknown aetiology, we performed high resolution in vitro proton nuclear magnetic resonance spectroscopy on patient cerebrospinal fluid (CSF) samples. We identified five adult patients, including two sisters, with significantly elevated free sialic acid in the CSF compared to both the cohort of patients with diseases of unknown aetiology (n = 144; P < 0.001) and a control group of patients with well-defined diseases (n = 91; P < 0.001). All five patients displayed cerebellar ataxia, with peripheral neuropathy and cognitive decline or noteworthy behavioural changes. Cerebral MRI showed mild to moderate cerebellar atrophy (5/5) as well as white matter abnormalities in the cerebellum including the peridentate region (4/5), and at the periventricular level (3/5). Two-dimensional gel analyses revealed significant hyposialylation of transferrin in CSF of all patients compared to age-matched controls (P < 0.001)—a finding not present in the CSF of patients with Salla disease, the most common free sialic acid storage disorder. Free sialic acid content was normal in patients’ urine and cultured fibroblasts as were plasma glycosylation patterns of transferrin. Analysis of the ganglioside profile in peripheral nerve biopsies of two out of five patients was also normal. Sequencing of four candidate genes in the free sialic acid biosynthetic pathway did not reveal any mutation. We therefore identified a new free sialic acid syndrome in which cerebellar ataxia is the leading symptom. The term CAFSA is suggested (cerebellar ataxia with free sialic acid)

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial.

Background Coronary artery bypass grafting (CABG) is the standard treatment for revascularization in patients with left main coronary artery (LMCA) disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We compared PCI and CABG for treatment of LMCA disease. Methods Patients with LMCA disease were enrolled in 36 centers and randomized 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris or non-ST elevation myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE) - a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularization and stroke. The primary outcome was test for non-inferiority of PCI to CABG after up to 5 years of follow-up. Results A total of 1201 patients were randomized. Kaplan-Meier five-year estimates of MACCE were 28.7% for PCI and 20.1% for CABG, HR 1.46 [95% confidence interval (CI), 1.10 to 1.95], exceeding the limit for non-inferiority and significant for superiority of CABG over PCI (p=0.0078). Comparing PCI to CABG, five-year estimates were 11.5% vs. 9.5% [HR 1.04 (95% CI, 0.65 to 1.67), p=0.86] for all-cause mortality; 6.9% vs. 1.9% [HR 2.9 (95% CI, 1.40 to 5.90), p=0.004] for non-procedural myocardial infarction; 16.2% vs. 10.4% [HR 1.5 (95% CI, 1.04 to 2.17), p=0.03] for any revascularization; and 4.9% vs 1.7% [HR 2.3 (95% CI, 0.92 to 5.48), p=0.07] for stroke. Conclusion CABG provided a clinical outcome superior to PCI for treatment of LMCA disease.</p