MELAS stands for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. It is a mitochondrial disorder in which epilepsy is common and can occur either during stroke-like episodes or independently.
What causes MELAS?
Most cases are caused by pathogenic variants in mitochondrial DNA, especially the m.3243A>G variant in MT-TL1.
Because mitochondrial DNA is maternally inherited, family history may show affected relatives through the maternal line, but severity can differ greatly.
Stroke-like episodes are not ordinary strokes
MELAS stroke-like episodes do not follow normal arterial vascular territories.
They can cause cortical visual loss, weakness, aphasia, headaches, confusion and seizures.
Epilepsy
Both focal and generalised seizures can occur.
Seizures can accompany stroke-like episodes or occur separately.
Seizures can worsen stroke-like injury
Seizure activity and stroke-like episodes can interact, with prolonged seizures potentially contributing to further metabolic stress in affected cortex.
EEG
EEG can show focal or multifocal epileptiform abnormalities, especially during acute neurological episodes.
Continuous EEG may be required when non-convulsive status is suspected.
MRI
Characteristic lesions often cross vascular boundaries and can migrate over time.
Posterior cortical regions are frequently involved.
Lactic acidosis
Elevated lactate can support the diagnosis but is not present at all times and is not specific to MELAS.
Normal lactate does not exclude mitochondrial disease.
Other clinical clues
Recurrent migraine-like headaches, vomiting, short stature, hearing impairment, exercise intolerance, diabetes, neuropathy and cardiomyopathy can occur.
Treatment of epilepsy
Antiseizure treatment is individualised.
Medication choices should consider mitochondrial toxicity, liver function, cardiac involvement and the person’s wider phenotype.
Valproate caution
Valproate is generally avoided or used with extreme caution in mitochondrial disorders where POLG disease has not been excluded, particularly in severe childhood phenotypes.
Stroke-like episode management
Management differs from conventional ischaemic stroke care because the underlying mechanism is metabolic rather than thromboembolic.
Treatment commonly involves urgent metabolic, neurological and seizure management.
Arginine
Intravenous or oral arginine has been used during or around stroke-like episodes in some specialist protocols.
Evidence is mixed and practice varies internationally, so it should not be portrayed as a universally proven standard.
Genetic testing
Testing may require blood, urine or other tissues because heteroplasmy levels differ across tissues and can fall in blood with age.
A negative blood test for a suspected mitochondrial DNA variant does not always end the investigation.
Inheritance
Mitochondrial DNA disorders are usually maternally inherited.
All children of an affected woman may inherit the variant, but the proportion of abnormal mitochondrial DNA and clinical severity can vary substantially.
Worldwide access
MELAS diagnosis may require MRI, metabolic testing and specialised mitochondrial genetic analysis.
These investigations remain unevenly available worldwide.
The central point
MELAS stroke-like episodes are metabolic brain events, not ordinary vascular strokes, and epilepsy is often an integral part of those episodes.
Related reading
Mitochondrial Epilepsy →
POLG-Related Epilepsy →
Sources
Medical note: acute neurological deterioration with seizures in suspected MELAS requires urgent specialist assessment.
Evidence checked: September 2026.