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Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS

MELAS presents with "stroke-like" episodes, typically in childhood or early adulthood (90% before age 40), characterized by multifocal cortical lesions crossing vascular territories with a predilection for posterior parietal and occipital lobes.

Key Images

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Look For First
  • Multifocal stroke-like cortical lesions that do NOT conform to single vascular territories
  • Swollen gyri with increased T2 signal in parieto-occipital and parieto-temporal regions
  • Lesions in different stages of evolution showing 'shifting spread' pattern crossing vascular boundaries
Key Image Findings
  • T2/FLAIR shows swollen gyri with increased signal in parieto-occipital and parieto-temporal regions that do not conform to standard vascular territories, distinguishing MELAS from typical arterial infarcts.
  • DWI/ADC shows increased DWI signal (b=1000) with variable ADC values: reduced ADC indicates cytotoxic edema while increased ADC (T2 shine-through) indicates vasogenic edema, often with both patterns coexisting within the same lesion.
  • MR spectroscopy may reveal elevated lactate peak in otherwise normal-appearing brain parenchyma or CSF, providing important diagnostic confirmation of metabolic dysfunction.
  • Acute lesions mimic infarcts but demonstrate multifocal involvement crossing multiple cerebral vascular territories (anterior, middle, posterior) rather than respecting single arterial distributions.
  • Enhancement of gyri on post-contrast imaging correlates with blood-brain barrier breakdown and reperfusion hyperemia, visible as blush on DSA/angiography.
  • Subacute to chronic phases show variable evolution: some lesions resolve with minimal permanent changes while others progress to encephalomalacia with 'black toenail sign' (cortical and subcortical necrosis).
  • Basal ganglia calcification is a characteristic finding, more prominent in older patients, reflecting chronic metabolic insult.
  • Cerebral and cerebellar atrophy may develop with recurrent lesions, and lesions may demonstrate 'shifting spread' pattern across different anatomic regions on serial imaging.
Differential Diagnosis
  • Acute ischemic stroke (embolism/dissection): confined to single vascular territory; MELAS crosses territories and shows vasogenic + cytotoxic edema pattern
  • Posterior reversible encephalopathy syndrome (PRES): typically bilateral and symmetric; MELAS often asymmetric with vasogenic edema and lactate on spectroscopy
  • Viral encephalitis: diffuse involvement with limbic predilection; MELAS shows cortical lesions in parieto-occipital distribution with elevated lactate
  • CADASIL: lesions predominantly subcortical white matter; MELAS shows cortical predominance with crossing of vascular territories
  • Cerebral vasculitis: may show multifocal lesions but lacks the characteristic elevated lactate on MR spectroscopy seen in MELAS
  • Status epilepticus: can cause DWI abnormalities but lacks the multi-territorial cortical involvement and elevated lactate of MELAS
Discussion

MELAS results from respiratory chain defect causing NAD+/NADH imbalance, leading to shift to anaerobic metabolism with lactate accumulation; this renders the cortex susceptible to neuronal death and vessel dysfunction.

The m.3243A>G point mutation in mtDNA (accounting for ~80% of cases) encodes tRNA for leucine and impairs mitochondrial protein production affecting multiple respiratory chain complexes.

Variable severity between patients with the same mutation reflects different percentages of mutated mtDNA in different tissues (heteroplasmy), with higher mutant burden causing more severe disease.

MELAS lesions demonstrate both cytotoxic and vasogenic edema patterns, reflecting the dual pathology of metabolic dysfunction and vascular compromise from mitochondrial angiopathy.

Serial imaging shows 'shifting spread' pattern with recurrent lesions in different locations during acute episodes, distinguishing the relapsing-remitting course from single-territory stroke.

Elevated lactate on MR spectroscopy can appear in otherwise normal-appearing brain, making it a sensitive diagnostic clue for metabolic dysfunction even when morphologic changes are subtle.

Reporting Pearls

Report multifocal cortical T2/FLAIR hyperintensities with gyral swelling in parieto-occipital and parieto-temporal regions that CROSS vascular territories; specify that DWI shows restricted diffusion with variable ADC values (mixed cytotoxic and vasogenic edema); recommend MR spectroscopy to assess for elevated lactate as a diagnostic confirmation of MELAS.

Pitfalls
  • Confusing MELAS with acute ischemic stroke: remember that MELAS lesions do NOT respect vascular territories and show variable ADC values (both restricted and increased), whereas typical strokes are confined to single arterial distributions with uniformly restricted diffusion.
  • Assuming normality on conventional MRI excludes MELAS: MR spectroscopy may demonstrate elevated lactate in normal-appearing parenchyma, so spectroscopy is essential for diagnosis.
  • Mistaking basal ganglia calcification in older MELAS patients for a separate calcifying process: recognize this as a chronic feature of MELAS, not unrelated pathology.
  • Using sodium valproate or metformin for seizures or diabetes in MELAS patients: these agents interfere with mitochondrial function and can worsen disease manifestations and lactic acidosis.
Source: Reference source

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