L-Arginine Dosage for MELAS Syndrome Management
For patients with MELAS syndrome, the recommended dose of L-arginine is 600 mg/kg/day for patients weighing less than 20 kg and 12 g/m² for patients weighing more than 20 kg, administered as both acute treatment for stroke-like episodes and maintenance therapy. 1
Dosing Regimen
Acute Treatment (Intravenous Administration)
- For stroke-like episodes, L-arginine hydrochloride should be administered intravenously 1:
- Weight <20 kg: 600 mg/kg given over 90 minutes as bolus, then as maintenance over 24 hours
- Weight >20 kg: 12 g/m² given over 90 minutes as bolus, then as maintenance over 24 hours
Maintenance Therapy (Oral Administration)
- For prevention of stroke-like episodes, oral L-arginine should be administered to maintain plasma arginine concentration at least 168 μmol/L 2, 3:
- Same dosing as acute treatment but administered orally for long-term maintenance
Clinical Evidence and Rationale
- L-arginine serves as a nitric oxide precursor that improves endothelial function through flow-mediated vasodilation in MELAS patients 4, 5
- Clinical trials have demonstrated that systematic administration of L-arginine significantly improves survival compared to natural history 2
- A 9-year prospective multicenter clinical trial showed that oral L-arginine extended the interictal phase and decreased the incidence and severity of stroke-like episodes 3
- Intravenous L-arginine improved symptoms including headache, nausea/vomiting, impaired consciousness, and visual disturbances during acute episodes 3, 6
Monitoring Parameters
- Plasma arginine levels should be monitored and maintained above 168 μmol/L, as stroke-like episodes have been observed to develop when levels fall below this threshold 2, 3
- Monitor for potential adverse effects including hypotension, especially in patients simultaneously receiving hemodialysis 1
- Evaluate clinical response through assessment of neurological symptoms and frequency of stroke-like episodes 3, 7
Important Considerations
- L-arginine therapy should be initiated promptly within 6 hours of onset of stroke-like symptoms for maximal efficacy 3, 6
- The dose may need to be titrated or reduced in patients with hypotension or those receiving hemodialysis 1
- No treatment-related serious adverse events have been reported in clinical trials of L-arginine for MELAS, and the formulations are generally well-tolerated 3
Cautions and Contraindications
- Monitor for potential hypotension, especially when administering intravenous formulations 1
- Consider potential drug interactions with medications that affect vascular tone or blood pressure 1
- Dosage may need adjustment in patients with renal impairment 1
This therapeutic approach has been shown to significantly improve outcomes in MELAS patients, with studies demonstrating both reduction in acute symptoms and long-term prevention of stroke-like episodes when appropriate dosing is maintained 2, 3, 7.