Management and Treatment of MELAS Syndrome
L-arginine is the primary treatment for MELAS syndrome, administered both acutely during stroke-like episodes and as chronic maintenance therapy to prevent recurrences. 1, 2
Acute Management of Stroke-Like Episodes
Administer intravenous L-arginine hydrochloride immediately when a stroke-like episode occurs:
- For patients <20 kg: 600 mg/kg IV over 90 minutes as bolus, then continue as maintenance over 24 hours 2
- For patients >20 kg: 12 g/m² IV over 90 minutes as bolus, then continue as maintenance over 24 hours 2
- This acute therapy improves headache, nausea/vomiting, impaired consciousness, and visual disturbances 1
- Monitor for hypotension during IV administration and adjust in patients with renal impairment 2
The mechanism works through L-arginine's role as a nitric oxide precursor, improving endothelial function via flow-mediated vasodilation, which addresses the underlying vascular dysfunction in MELAS 1, 3
Chronic Maintenance Therapy
Continue oral L-arginine indefinitely to prevent stroke-like episodes:
- Same weight-based dosing as acute treatment: 600 mg/kg/day for <20 kg or 12 g/m²/day for >20 kg, administered orally 2
- This maintenance therapy extends the interictal phase between stroke-like episodes 1
- The goal is to maintain plasma arginine concentrations continuously 2
Adjunctive Supportive Therapies
While L-arginine is the primary evidence-based treatment, several adjunctive agents support mitochondrial function, though they lack the same level of evidence:
Coenzyme Q10 and related compounds:
- Idebenone (synthetic coenzyme Q10 analogue) supports the electron transport chain 1, 3
- Standard coenzyme Q10 is commonly used despite limited proven efficacy 4
Vitamins and cofactors:
- Vitamin C as an antioxidant to support mitochondrial function 1, 3
- Riboflavins to support the electron transport chain 3
- B vitamins for general mitochondrial support 5
Metabolic modulators:
Multidisciplinary Symptom Management
Address specific organ system complications as they arise:
Neurological:
- Manage seizures with appropriate anticonvulsants (MELAS patients commonly present with seizures) 1, 3
- Treat migraine-like headaches 3
Cardiac:
Endocrine:
- Screen for and treat diabetes mellitus (common manifestation) 1, 5
- Evaluate for growth hormone deficiency if short stature is present 6
Sensory:
- Monitor for bilateral sudden neurosensory hearing loss, which should raise immediate suspicion for MELAS when combined with elevated lactate 1
Metabolic:
- Monitor serum lactate levels, particularly during acute episodes 7
Diagnostic Confirmation
Key diagnostic features to establish MELAS diagnosis:
- Stroke-like episodes that don't conform to specific arterial territories, preferentially involving posterior cerebral hemispheres 3
- Exercise intolerance with onset before age 40 1, 3
- Elevated serum lactate, especially during acute episodes 7
- Muscle biopsy showing ragged-red fibers 1, 3
- Genetic testing for A3243G mutation in mitochondrial DNA (present in ~80% of cases) 1, 3
Critical Caveats
Anesthetic considerations: Patients with MELAS have enhanced sensitivity to neuromuscular blockade and anesthetic agents, with potential susceptibility to malignant hyperthermia 8. Regional anesthesia may be preferable when neurological abnormalities of the spinal cord or peripheral nerves are ruled out 8.
Evidence limitations: The rarity of MELAS makes generating high-quality randomized controlled trial data challenging 1. Optimal dosage, timing, and duration of L-arginine therapy remain to be fully established through rigorous trials 1. However, unblinded studies demonstrate clear benefit for L-arginine in improving stroke-like episode symptoms and reducing their frequency and severity 4.