Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with an MT-TL1 m.3243A>G point mutation: Neuroradiological features and their implications for underlying pathogenesis

Helin Zheng; Xuemei Zhang; Lu Tian; Bo Liu; Xiaoya He; Longlun Wang; Shuang Ding; Yi Guo; Jinhua Cai

doi:10.3389/fnins.2022.1028762

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with an MT-TL1 m.3243A>G point mutation: Neuroradiological features and their implications for underlying pathogenesis

Front Neurosci. 2023 Jan 6:16:1028762. doi: 10.3389/fnins.2022.1028762. eCollection 2022.

Authors

Helin Zheng¹, Xuemei Zhang², Lu Tian¹, Bo Liu¹, Xiaoya He¹, Longlun Wang¹, Shuang Ding¹, Yi Guo³, Jinhua Cai¹

Affiliations

¹ Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Department of Radiology, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
² Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Department of Medical Affairs, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
³ Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Department of Pediatric Neurology, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Objective: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common inherited mitochondrial disorders. Due to the high clinical and genetic heterogeneity of MELAS, it is still a major challenge for clinicians to accurately diagnose the disease at an early stage. Herein, we evaluated the neuroimaging findings of MELAS with an m.3243A>G mutation in MT-TL1 and analyzed the possible underlying pathogenesis of stroke-like episodes.

Materials and methods: Fifty-nine imaging studies in 24 patients who had a confirmed genetic diagnosis of m.3243A>G (MT-TL1; tRNA ^Leu) associated with MELAS were reviewed in our case series. The anatomic location, morphological features, signal/intensity characteristics and temporal evolution of lesions were analyzed on magnetic resonance imaging (MRI), and computed tomography (CT) images. The supplying vessels and metabolite content of the lesions were also evaluated by using MR angiography (MRA)/CT angiography (CTA), and MR spectroscopy (MRS), respectively.

Results: The lesions were most commonly located in the posterior brain, with 37 (37/59, 63%) in the occipital lobe, 32 (32/59, 54%) in the parietal lobe, and 30 (30/59, 51%) in the temporal lobe. The signal characteristics of the lesions varied and evolved over time. Bilateral basal ganglia calcifications were found in 6 of 9 (67%) patients who underwent CT. Cerebral and cerebellar atrophy were found in 38/59 (64%) and 40/59 (68%) patients, respectively. Lesion polymorphism was found in 37/59 (63%) studies. MRS showed elevated lactate doublet peaks in 9/10 (90%) cases. MRA or CTA revealed that the lesion-related arteries were slightly dilated compared with those of the contralateral side in 4 of 6 (67%) cases.

Conclusion: The imaging features of MELAS vary depending on the disease stage. Polymorphic lesions in a single imaging examination should be considered a diagnostic clue for MELAS. Stroke-like episodes may be involved in a complex pathogenetic process, including mitochondrial angiopathy, mitochondrial cytopathy, and neuronal excitotoxicity.

Keywords: MELAS; m.3243A>G; neuroradiological features; polymorphic lesions; stroke-like episodes.