Forecasting stroke-like episodes and outcomes in mitochondrial disease

作者：Yi Shiau Ng, Nichola Zoe Lax, Alasdair P. Blain, Daniel Erskine, Mark R. Baker, Tuomo M. Polvikoski, Rhys Huw Thomas, Christopher M. Morris, Ming Lai, Roger G. Whittaker, Alasdair Gebbels, Amy Winder, Julie Hall, Catherine L Feeney, Maria Elena Farrugia, Claire L. Hirst, Mark Roberts, Charlotte Lawthom, Alexia Chrysostomou, Kevin J. Murphy, Tracey Anne Baird, Paul Maddison, Callum W. Duncan, Joanna Poulton, Victoria Nesbitt, Michael G. Hanna, Robert D. S. Pitceathly, Robert William Taylor, Emma L. Blakely, Andrew M. Schaefer, Douglass M. Turnbull, Robert McFarland, Gráinne S. Gorman · 发表于：Brain · 年份：2021 · DOI：10.1093/brain/awab353 · 被引用次数：73 · 研究领域：Mitochondrial Function and Pathology、Metabolism and Genetic Disorders、ATP Synthase and ATPases Research

In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes and to identify associated risk predictors. Between January 1998 and June 2018, we identified 111 patients with genetically determined mitochondrial disease who developed stroke-like episodes. Post-mortem cases of mitochondrial disease (n = 26) were identified from Newcastle Brain Tissue Resource. The primary outcome was to interrogate the clinico-radiopathological correlates and prognostic indicators of stroke-like episode in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS). The secondary objective was to develop a multivariable prediction model to forecast stroke-like episode risk. The most common genetic cause of stroke-like episodes was the m.3243A>G variant in MT-TL1 (n = 66), followed by recessive pathogenic POLG variants (n = 22), and 11 other rarer pathogenic mitochondrial DNA variants (n = 23). The age of first stroke-like episode was available for 105 patients [mean (SD) age: 31.8 (16.1)]; a total of 35 patients (32%) presented with their first stroke-like episode ≥40 years of age. The median interval (interquartile range) between first and second stroke-like episodes was 1.33 (2.86) years; 43% of patients developed recurrent stroke-like episodes within 12 months. Clinico-radiological, electrophysiological and...