Multidimensional MRI is only one piece of the puzzle in the diagnosis of stroke-like episodes in MELAS

We reviewed the article by Yang et al. on a retrospective study of the validity of multidimensional magnetic resonance imaging (MRI) using magnetic resonance spectroscopy (MRS), perfusion-weighted imaging (PWI), and diffusion-weighted imaging (DWI) to distinguish stroke-like lesions (SLLs), the correlate of a stroke-like episode (SLE) in imaging, in the acute and chronic stage, in 24 patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome from ischemic stroke (IS) in 25 patients (1). MELAS patients in the acute stage of an SLL showed an increased lactate/creatine ratio and a decreased N-acetylaspartate (NAA)/creatine ratio, increased cerebral blood flow (CBF), and increased cerebral blood volume (CBV) (1). Lactate, CBF, and CBV were increased in MELAS patients and the most suitable parameters for distinguishing MELAS from IS (1). It was concluded that multiparametric MRI is useful for distinguishing between MELAS and IS (1). The study is noteworthy, but some points require discussion.

The first point relates to the retrospective design of the study. Retrospective designs have the disadvantage that data quality may be poor, data may be missing, evidence of causality is limited and only associations can be established, they are susceptible to memory and selection bias, control of confounding variables is difficult, and the level of evidence is generally lower compared to prospective studies (2). Accordingly, only 16 of 24 MELAS patients had dynamic contrast-enhanced (DCE) imaging, only 16 of 24 had MRS plus DCE, only 19 of 24 had MRS plus DWI, and only 16 had MRS, DCE, and DWI (1).

The second point is that the Japanese criteria for the diagnosis of MELAS were not met (3). According to the Japanese criteria, the detection of a pathogenic mutation in mtDNA or nDNA is a prerequisite for the diagnosis of MELAS. As long as no mutation was confirmed in any of the 24 patients included, they should not be diagnosed with MELAS solely on the basis of the presence of SLEs. SLEs can also occur in mitochondrial syndromes other than MELAS.

The third point is that no heteroplasmy rates were reported (1). Assuming that the 24 patients carried mtDNA variants, it would have been essential to report the ratio of mutated mtDNA to wild-type mtDNA in order to establish a possible genotype-phenotype correlation and to target genetic counselling.

The fourth point is that we disagree with the statement that MRS, PWI, and DWI have not been used in combination to distinguish SLL from IS (1). A 61-year-old man with weakness of the right upper extremity, confusion, and migraine attacks on the right and left sides was initially diagnosed with IS and treated for acute IS (4). After multimodal MRI, MRS, and magnetic resonance angiography, the diagnosis was revised to MELAS with acute SLE (4).

The fifth point is that we disagree with the statement in the summary that it is difficult to distinguish between SLE and IS using conventional MRI sequences (1). SLE is hyperintense on T2/fluid-attenuated inversion recovery (FLAIR), DWI, and PWI from the outset and is not limited to a vascular area. IS, on the other hand, is T2/FLAIR isointense in the acute stage, limited to a vascular area, and only hyperintense on DWI (5).

In summary, conventional MRI allows a distinction to be made between IS and SLL. The diagnosis of MELAS should not be based solely on MRI, but should also take into account the phenotype and genotype.

Appendix 1: Response to “Multidimensional MRI is only one piece of the puzzle in the diagnosis of stroke-like episodes in MELAS”.

Acknowledgments

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Footnote

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2171/coif). The author has no conflicts of interest to declare.

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