PMC6365425_01
Temporal evolution of brain magnetic resonance imaging (MRI). FLAIR (fluid attenuated recovery) sequences are shown in the upper line, and DWI (diffusion-weighted imaging) sequences are shown in the lower line. (A) First stroke-like episode initially interpreted as an ischemic stroke. A high signal occurred in the diffusion-weighted imaging (DWI) sequences in the right temporo-occipital lobes and the corresponding fluid attenuated recovery (FLAIR) sequence. (B) Second stroke-like episode: three months later, evidence of a wider lesion was found in the right temporal, parietal and occipital lobes together with initial enlargement of the ventricular spaces. (C) Third stroke-like episode: a new cortical DWI abnormality was observed in the left medial temporal and occipital lobes; marked and diffuse atrophy was found in the brain parenchyma.
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F1
Brain computed tomography (CT) and MRI showed a right temporo-occipital lesion with a high signal in the diffusion-weighted imaging (DWI) sequences, which was interpreted as an ischemic stroke (Figure 1A). The brain MRI was repeated and showed evolution of the right hemispheric lesion, which extended to the parietal lobe and the anterior and medial parts of the temporal lobe and involved the subcortical white matter and cortex (Figures 1B, 2A,B). Figure 1. Four of these family members were positive for heteroplasmy and were asymptomatic. A partial resolution of the previous right cortical lesion and the presence of a new cortical DWI abnormality in the left medial temporal and occipital lobes was observed at the brain MRI (Figure 1C, lower part), revealing a new stroke-like episode. Additionally, the Fluid Attenuated Recovery (FLAIR) sequences identified a marked and greater cortical atrophy with increased ventricular sizes (Figure 1C, upper part).
Diagnostic assessment of MELAS syndrome. (A-B) Cortical diffusion-weighted imaging abnormalities in the right temporal, parietal and occipital lobes with corresponding fluid attenuated inversion recovery hyperintensity. (C) Brain positron emission tomography (PET) revealed a severe reduction in cortical glucose metabolism in the posterior right hemisphere. (D) MR spectroscopy (MRS) showed elevation of the lactate peak within the abnormal lesion. (E-H) Muscle biopsies. (E) Modified Gomori Trichrome stain (40X) showing a typical Ragged Red muscle fiber (RRF) containing mitochondrial hyperproliferation. (F) Succinate dehydrogenase (SDH) stain (40X) confirming mitochondrial hyperproliferation in the same fiber. (G) Cytochrome C oxidase (COX) stain (40X) demonstrating muscle cells with decreased mitochondrial activity. (H) COX/SDH combo reaction (20X) showing diffuse fibers with COX deficiency and SDH positivity scattered in the muscle.
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The brain MRI was repeated and showed evolution of the right hemispheric lesion, which extended to the parietal lobe and the anterior and medial parts of the temporal lobe and involved the subcortical white matter and cortex (Figures 1B, 2A,B). The electroencephalogram (EEG) showed slow persistent activity and periodic lateralized epileptiform discharges (PLEDs) in the right hemisphere, whereas the brain PET revealed a severe reduction in cortical glucose metabolism in the posterior right hemisphere (Figure 2C). To confirm this hypothesis, the patient underwent MR spectroscopy (MRS) and demonstrated elevation of the lactate peak within the abnormal lesion (Figure 2D), a muscle biopsy that was consistent with mitochondrial myopathy (Figures 2E-H) and genetic testing, which revealed the presence of a mitochondrial DNA mutation (m.3243A>G) (heteroplasmy 13.1%) in the MT-TL1 gene encoding the leucine transfer RNA.
Timeline representing the clinical disease course. Major clinical episodes are shown in the first line, and the diagnostic assessments performed and treatments are reported in the second and third lines, respectively. IPO, intestinal pseudo-obstruction; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; PLED, period lateralized epileptiform discharges.
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Despite therapeutic implementation, the patient did not recover, and he died one month later (Figure 3).