Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS)
General description
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is the most common form of mitochondrial encephalopathy, although it remains a rare genetic disorder. It is maternally inherited, typically caused by a point mutation at A3243G in the mitochondrial tRNA LEU gene. MELAS presents with a wide range of symptoms, often beginning in childhood but potentially appearing later in life. Common features include stroke-like episodes (with symptoms such as headache, vomiting, seizures, hemiplegia, cortical blindness, and visual field defects), short stature, progressive cognitive impairment, muscle weakness, hearing loss, and diabetes.
Laboratory findings often reveal elevated lactate levels in blood or cerebrospinal fluid, as well as mitochondrial abnormalities in muscle biopsy. Stroke-like episodes in MELAS are characterized by brain lesions that do not conform to vascular territories, frequently affecting the temporal and occipital lobes, leading to symptoms like visual disturbances, ataxia, and neuropsychiatric issues. Unlike typical stroke, these episodes usually present with headache, vomiting, and seizures rather than sudden-onset speech or motor deficits. Other systemic symptoms can include gastrointestinal dysmotility, pseudo-obstruction, hirsutism, and renal tubular acidosis. Family history may reveal related conditions such as migraine-like headaches, sensorineural hearing loss, diabetes, hypertrophic cardiomyopathy, and progressive external ophthalmoplegia.
MR spectroscopy
MRS reveals elevated lactate and decreased NAA during the acute phase.
Basal ganglia and dentate nuclei calcification
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Caudate nucleus
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Putamen
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Globus pallidus
CT shows mild bilateral symmetric calcification of the basal ganglia and dentate nuclei, particularly in the globus pallidus.
Cerebellar atrophy
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Cerebellum
Common findings in mitochondrial encephalomyopathy include cerebellar atrophy prior to stroke-like episodes.
Stroke-like episode
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CerebrumOccipital lobeCerebral cortex
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CerebrumOccipital lobeCerebral white matterSubcortical white matter
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CerebrumTemporal lobeCerebral cortex
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CerebrumTemporal lobeCerebral white matterSubcortical white matter
MRI shows hyperintensity with swelling in the cerebral cortex and subcortical white matter of the occipital and parietal lobe, while the periventricular white matter is typically spared. The distribution of the lesions does not correspond to vascular perfusion areas, and contrast enhancement may be observed in the cortex. During stroke-like episodes, the lesions may slowly progress to the surrounding cortex over several weeks, a characteristic feature of MELAS.
Unlike in infarction, vascular perfusion is increased in the affected lesions, as indicated by elevated signals on SPECT and arterial spin labeling (ASL), along with arterial dilation on MRA. ASL is more sensitive than MRA, making it the recommended modality for evaluation.
DWI shows hyperintensity, while ADC may show either hyperintensity or hypointensity.
Arterial dilation
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ArteryPosterior cerebral artery (PCA)
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ArteryMiddle cerebral artery (MCA)