“Strokes” in MELAS are Actually Stroke-like Episodes Due To Metabolic Pathophysiology
Year: 2024
Type: article
Abstract: Sir, The article by Mahesan et al.[1] on a 9-month-old male with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) due to the mtDNA variant m. 1630A>G in MT-TV1 is interesting, but needs to be discussed. The first point is that the index patient did not suffer from “infarcts” (ischemic strokes) but from stroke-like episodes (SLEs), the morphologic equivalent of which can be seen on MRI in Figure 1.[1] These lesions are known as stroke-like lesions (SLLs) and show a typical pattern on multimodal MRI.[2] They are hyperintense on T2/FLAIR, DWI, and PWI and hypointense on OEF.[2] They do not correspond to a vascular territory, initially expanding to a nadir and then regressing to normality or to a residual structural lesion (e.g., atrophy, cyst, white matter lesion, laminar cortical necrosis, toenail sign).[2] On FDG-PET, they exhibit hypometabolism and MR spectroscopy shows a reduced NAA peak and an increased lactate peak.[2] The second point is that heteroplasmy rates of the causative mtDNA variant in the most clinically affected tissues or organs were not reported.[1] Knowledge of heteroplasmy rates is important not only for establishing a genotype-phenotype correlation, but also for assessing genotypic heterogeneity within a family and for genetic counseling. Third, whether the causative variant was sporadic or maternally inherited was not investigated.[1] Was there a family history of positive phenotypic features of mitochondrial disorder (MID) in first-degree relatives, and did clinically affected or unaffected relatives test positive for the mtDNA variant of the index patient? The fourth point is that MELAS was diagnosed based on the presence of an mtDNA variant, but not according to established diagnostic criteria, such as the Japanese or Hirano criteria. Did the patient fulfill these criteria? The fifth point is that SLEs were obviously not treated in the acute stage. Several studies have shown that MID patients with SLE potentially benefit from the administration of NO precursors such as L-arginine or L-citrulline.[3] The sixth point is that the index patient has not been prospectively studied for multisystem involvement. Since MELAS and MIDs are generally multisystem diseases, patients need to be systematically screened for multiorgan involvement. In summary, MELAS patients and their families need comprehensive genetic and clinical investigations to assess the extent and prognosis of the disease. Author contribution JF was responsible for the design and conception, discussed available data with coauthors, wrote the first draft, and gave final approval. SZ: contributed to literature search, discussion, correction, and final approval. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Neurology India
Author: Josef Finsterer
Institution: University of Vienna
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4405551000