Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of many mitochondrial disorders. As mitochondria, which have their own DNA, are exclusively passed on from the mother, these disorders are only maternally inherited.
On imaging, it manifests as multifocal stroke-like cortical lesions in different stages of evolution ("shifting spread" pattern), crossing the cerebral vascular territories, and showing a certain predilection to the posterior parietal and occipital lobes. MR spectroscopy may demonstrate elevated lactate in an otherwise normal appearing brain 3.
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Epidemiology
As the name suggests, MELAS is characterized by 'stroke-like' episodes, typically in childhood or early adulthood (90% present before 40 years of age).
Clinical presentation
MELAS usually has a relapsing-remitting course, with or without superimposed accretion of permanent deficits. Clinical presentation is highly variable between patients (even from the same affected family), with potential clinical features including 1,6,7:
stroke-like episodes (e.g. hemiparesis, hemianopia)
lactic acidosis
encephalopathy, including seizures and migraine-like headaches
dementia
proximal muscle weakness (myopathy)
peripheral neuropathy
short stature
Pathology
The defect involves the respiratory chain, which is responsible for energy production 7. A point mutation at mtDNA nucleotide 3243 (A to G translocation) which encodes for transfer RNA (tRNA) for leucine is the most common cause (~80%) of the condition 7. It is therefore thought that this abnormality results in abnormal protein production throughout the mitochondria and affects multiple parts of the respiratory chain. The exact mechanism notwithstanding, the net result is depletion of NAD+ and NADH+. This, in turn, results in a shift to anaerobic metabolism accounting for the buildup of lactic acid and renders the cortex susceptible to neuronal death 1.
As some mitochondria are passed in the ovum, not all will have the mutant mtDNA. The percentage of mutated genes will affect the severity of clinical manifestations 1.
Diagnosis
To make the diagnosis of MELAS identification of the most common pathogenic mtDNA variant (m.3243A>G) can be made on peripheral blood samples in 80% of patients. To identify non-m.3243A>G mutations additional testing or muscle biopsy may be required 5.
Radiographic features
CT
-
multiple infarcts
involving multiple vascular territories
may be either symmetrical or asymmetrical
parieto-occipital and parieto-temporal involvement is most common
-
basal ganglia calcification 1,2
more prominent feature in older patients
atrophy 2
MRI
-
acute infarcts
-
chronic infarcts
involving multiple vascular territories
may be either symmetrical or asymmetrical
the black toenail sign may be present in the subacute phase
parieto-occipital and parieto-temporal regions most common
MR spectroscopy: may demonstrate elevated lactate in otherwise normal appearing brain parenchyma or in CSF 3,4.
Digital subtraction angiography (DSA)
usually normal
enhancing gyri, presumably due to the breakdown of the blood-brain barrier and reperfusion hyperemia correlating with a blush on angiography 2
Treatment and prognosis
There is no disease-modifying treatment. Substances such as L-arginine, taurine and coenzyme Q10 are thought to aid in increasing energy production by mitochondria and may slow the effects of the disease.
Antiseizure medications should be used for symptomatic treatment of seizures. However, those that interfere with respiratory chain function, such as sodium valproate, are avoided due to the potential of aggravating manifestations of MELAS.
Differential diagnosis
Possible differential considerations include:
-
other mitochondrial disorders
-
ischemic strokes, due to
embolism
dissection
CADASIL: lesions are not subcortical
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