Treatment of MELAS Syndrome
L-arginine therapy is the primary treatment for MELAS syndrome, administered both acutely during stroke-like episodes and as chronic maintenance therapy to prevent recurrence. 1, 2
Acute Management of Stroke-Like Episodes
L-Arginine Administration (First-Line)
- Administer intravenous L-arginine hydrochloride immediately using weight-based dosing: 2
- Patients <20 kg: 600 mg/kg IV
- Patients >20 kg: 12 g/m² IV
- Infuse over 90 minutes as initial bolus, then continue as maintenance infusion over 24 hours 2
- This improves acute symptoms including headache, nausea/vomiting, impaired consciousness, and visual disturbances 1
Supportive Acute Care
- Aggressive seizure control with antiepileptic drugs is required, as seizures are a cardinal feature and can worsen metabolic decompensation 1
- Intubation and mechanical ventilation may be necessary if the patient has depressed consciousness or active seizures to normalize PaCO2 and prevent neurologic deterioration 1
- Measure serum lactate immediately as elevated levels are a diagnostic hallmark 1
- Consider IV sodium bicarbonate for severe metabolic acidosis 1
- Provide adequate oxygen if hypoxemia develops—the mechanism differs fundamentally from COPD, so do not withhold oxygen 1
Chronic Maintenance Therapy
L-Arginine (Primary Prevention)
- Oral L-arginine daily to extend the interictal phase between stroke-like episodes: 1, 2
- Patients <20 kg: 600 mg/kg/day orally
- Patients >20 kg: 12 g/m²/day orally
- This is the only therapy with evidence for preventing stroke-like episodes 1, 3
- Monitor for hypotension, especially with IV formulations 2
- Adjust dosage in renal impairment 2
Adjunctive Mitochondrial Support Therapies
While L-arginine is the primary evidence-based treatment, the following adjunctive therapies are commonly used to support mitochondrial function, though their efficacy is not definitively proven: 4, 5, 3
- Coenzyme Q10 (idebenone): Synthetic analog supporting electron transport chain 4, 5
- Vitamin C: Antioxidant supporting mitochondrial function 4, 6
- B vitamins (especially riboflavin): Support electron transport chain 4, 5
- Levocarnitine: Commonly prescribed though efficacy unproven 5, 3
- Dichloroacetate: May reduce lactic acid levels 4
Management During Intercurrent Illness
Infection Management
- Aggressive hydration with IV fluids 1
- Antipyretics for fever 1
- Enforce rest and avoid physical exertion 1
- Consider prophylactic antibiotics for high fever with respiratory symptoms 1
- Monitor closely for stroke-like episodes, altered consciousness, and respiratory distress—seek immediate medical attention if these develop 1
- Check serum lactate if symptoms worsen 1
Critical Pitfalls to Avoid
- Do not interpret elevated CO2 as simply a ventilation problem—it typically reflects the body's inability to compensate for severe metabolic acidosis from mitochondrial dysfunction 1
- Do not withhold oxygen in hypoxemic MELAS patients due to concerns about CO2 retention—the mechanism differs from COPD 1
- Do not delay L-arginine therapy during acute stroke-like episodes, as early administration improves outcomes 1, 3
- Recognize that optimal dosing, timing, and duration of L-arginine remain incompletely established due to the rarity of MELAS making high-quality trials challenging 1
Multidisciplinary Considerations
- Genetic counseling is essential for affected women, as heteroplasmy level (proportion of mutant mtDNA) determines disease severity in offspring 1
- Screen for multisystem complications: cardiac conduction defects, diabetes mellitus, hearing loss, myopathy, and gastrointestinal disorders 1, 4, 5
- Consider pulmonary hypertension screening as patients are at risk 1