Acute Cortical Lesions in MELAS Syndrome: Anatomic Distribution, Symmetry, and Evolution

Abstract

Background and purpose: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder affecting children and young adults. Stroke-like episodes are often associated with acute cortical lesions in the posterior cerebral cortex and are classically described as asymmetric and transient. In this study we assessed the anatomic distribution of acute cortical lesions, the incidence of symmetry, and the temporal evolution of lesions.

Materials and methods: This was a retrospective cohort study of patients who had a confirmed genetic diagnosis of a pathogenic variant associated with MELAS and MR imaging performed at our center (2006-2018). Each MR imaging study was assessed for new lesions using T1, T2, FLAIR, DWI, ADC, and SWI. The anatomic location, symmetry, and temporal evolution of lesions were analyzed.

Results: Eight patients with the same pathogenic variant of MELAS (MT-TL1 m.3243A>G) with 31 MR imaging studies were included. Forty-one new lesions were identified in 17 of the studies (5 deep, 36 cortical). Cortical lesions most commonly affected the primary visual cortex, the middle-third of the primary somatosensory cortex, and the primary auditory cortex. Thirty of 36 cortical lesions had acute cortical diffusion restriction, of which 21 developed cortical laminar necrosis on subacute imaging. Six of 11 studies with multiple lesions showed symmetric cortical involvement.

Conclusions: Acute cortical lesions in MELAS most commonly affect the primary visual, somatosensory, and auditory cortices, all regions of high neuronal density and metabolic demand. The most common pattern of temporal evolution is acute cortical diffusion restriction with subacute cortical laminar necrosis and chronic volume loss. Symmetric involvement is more common than previously described.

Fig 1.

Axial MR imaging shows temporal evolution of an acute cortical lesion in a patient with MELAS presenting with an acute stroke-like episode with left upper limb sensory loss. A, DWI (b = 1000) image from the day after symptom onset shows hyperintense intracortical signal in the middle-third of the right postcentral gyrus (hand/arm region of the primary somatosensory cortex). B, ADC image shows corresponding hypointense intracortical signal in keeping with diffusion restriction (white and black arrows). C, T2-weighted spin-echo image shows T2 hyperintensity in the deeper cortical layers and juxtacortical white matter (black arrow), with sparing of the superficial cortex (white arrow). D, Progress T2-weighted spin-echo image obtained 3 weeks later shows focal intracortical hypointense signal (black arrow) and mild volume loss, in keeping with pseudolaminar necrosis (black toenail sign).

Fig 2.

Axial MR imaging shows 4 examples of symmetric cortical involvement by acute lesions in patients with MELAS. A, T2-weighted spin-echo image shows symmetric hyperintense signal in the deep cortex and juxtacortical white matter of the bilateral medial frontal gyri, with sparing of the superficial cortex (typical for pseudolaminar involvement). B, T2-weighted spin-echo image shows symmetric hyperintense intracortical signal in the middle-thirds (black arrows) of the bilateral precentral gyri (hand regions of the primary motor cortex), with sparing of the superficial cortex. C, T2-FLAIR image shows symmetric cortical and subcortical hyperintense signal in the pericalcarine cortex of the bilateral medial occipital lobes (primary visual cortex). D, T2-FLAIR image shows symmetric cortical and subcortical hyperintense signal in the posterior halves of the bilateral superior temporal gyri (primary auditory cortex).