Altered Dynamic Functional Connectivity in Patients With Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes (MELAS) at Acute and Chronic Stages: Shared and Specific Brain Connectivity Abnormalities

Abstract

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the dynamic functional connectivity (dFC) of brain networks in MELAS has not been explored.

Purpose: To investigate the abnormalities of dFC in patients with MELAS at the acute and chronic stages, and to determine the possible relations between dynamic connectivity alterations and volumes of stroke-like lesions (SLLs).

Study type: Prospective.

Subjects: Twenty-two MELAS patients at the acute stage, 23 MELAS patients at the chronic stage, and 22 healthy controls.

Field strength/sequence: Single-shot gradient-recalled echo planar imaging (EPI) sequence at 3T.

Assessment: Dynamic FC states were estimated using the sliding window approach and k-means clustering analyses. Combined with graph theory, the topological properties of the dFC network were also accessed.

Statistical tests: Permutation test, Pearson correlation coefficient, and false discovery rate correction.

Results: We identified four dFC states and found that MELAS patients (especially at the acute stage) spent more time in a state with weaker connectivity (state 1) and less time in states with stronger connectivity. In addition, volumes of acute SLLs were positively correlated with mean dwell time in state 1 (r = 0.539, P < 0.05) and negatively correlated with the number of transitions (r = -0.520, P < 0.05). Furthermore, MELAS patients at the acute stage exhibited significantly increased global efficiency (P < 0.01) and decreased local efficiency (P < 0.001) compared to the controls and the patients at the chronic stage. Patients at the chronic stage only showed significantly (P < 0.001) decreased local efficiency compared to the controls.

Data conclusion: Our findings suggest similar and distinct dFC alterations in MELAS patents at the acute and chronic stages, providing novel insights for understanding the neuropathological mechanisms of MELAS. Level of Evidence 2 Technical Efficacy Stage Stage 2 J. MAGN. RESON. IMAGING 2021;53:427-436.

Keywords: dynamic functional connectivity; mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; resting-state functional magnetic resonance imaging; stroke-like episodes.