A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features
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To investigate a diversity of stroke-like episodes (SLEs) in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and report a disseminated form of SLEs (D-SLEs) attributed to a cluster of disseminated small cortical lesions.
We retrospectively reviewed the clinical information of 27 MELAS patients seen at Kitasato University Hospital between January 1990 and April 2018. Among those, we selected 13 patients with m.3243A>G mutation [median age at onset, 35 years (11–68 years), two pediatric onset < 17 years] who had at least one SLE. SLEs were classified into classic or non-classic based on characteristic features of stroke-like lesions.
44 SLEs were identified during a median observational period of 119 months (3–240 months). Among those, 29 (65.9%) were classic SLEs (C-SLEs) mainly attributed to a single continuous lobular lesion incongruent to vascular territory and occasionally accompanied by a gradual spread associated with hyperperfusion and persistent seizure activity. The remaining 15 were non-classic attributed to sparsely distributed (n = 10), disseminated (n = 4) or cerebellar lesions (n = 1). C-SLEs developed in all patients but non-classic SLEs in 5; D-SLEs developed in 4 patients accounting for 4 of 44 SLEs (9.1%). Non-classic SLEs developed more frequently in pediatric-onset than in adult-onset patients (12/15 vs. 3/29, p < 0.0001). SLEs began with acute onset of symptoms in 42 SLEs (95.5%), but D-SLEs of 2 adult-onset patients began with ill-defined subacute-onset fluctuating encephalopathy.
This study showed a diversity of SLEs in patients with m.3243A>G mutation. Further studies are required to elucidate the pathophysiological mechanisms of non-classic SLEs including D-SLEs.
KeywordsMELAS Stroke-like episodes Diversity Brain MRI Cerebral blood flow
The authors thank all of the patients involved in this study and acknowledge the efforts of research staff, who worked on the clinical and neuroimaging data collection.
YH, NK, TI: conception of the work, data acquisition, data interpretation, drafting and revising the manuscript for intellectual content. JK, HS, DI, EK, TA, YO, TG, KN: data acquisition, data interpretation, and revising the manuscript for intellectual content.
Compliance with ethical standards
Conflicts of interest
KN received grants from Daiichi Sankyo Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., and Eisai Co., Ltd. TI received a grant from Japan Epilepsy Research Foundation. Other authors report no disclosures.
The study was approved by the Institutional Review Board of Kitasato University (B17-351).
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