Treatment for MELAS Syndrome
L-arginine therapy is the primary treatment for MELAS syndrome, administered both as acute treatment for stroke-like episodes and as maintenance therapy to prevent recurrence. 1, 2
First-Line Treatment: L-arginine
Acute Treatment for Stroke-Like Episodes
- Intravenous L-arginine hydrochloride should be administered with the following weight-based dosing regimen 1, 2:
- For patients weighing <20 kg: 600 mg/kg
- For patients weighing >20 kg: 12 g/m²
- Administered over 90 minutes as bolus, then as maintenance over 24 hours 2
- May improve acute symptoms including headache, nausea/vomiting, impaired consciousness, and visual disturbances 1
- Monitor for potential hypotension, especially with intravenous administration 2
Maintenance Therapy
- Oral L-arginine at the same dosing as acute treatment but administered orally for long-term maintenance 1, 2
- Helps extend the interictal phase of stroke-like episodes 1
- Dosage may need adjustment in patients with renal impairment 2
Supportive Treatments
Mitochondrial Support Agents
- Coenzyme Q10 and its synthetic analog idebenone support mitochondrial function 1, 3, 4
- Vitamin C serves as an antioxidant to support mitochondrial function 1, 3
- Riboflavin helps support the electron transport chain 3
- Levocarnitine (L-carnitine) is commonly used to support mitochondrial function 4, 5
- B vitamins are frequently prescribed to support mitochondrial metabolism 4
Management of Specific Symptoms
- Anticonvulsants for seizure control, which are common in MELAS 3, 5
- Consider modified ketogenic diet as an adjunctive therapy, which may improve mitochondrial function and provide better seizure control 6
- Dichloroacetate may help reduce lactic acid levels 1, 3
Monitoring and Follow-up
- Regular monitoring of lactic acid levels 1, 7
- Surveillance for multisystem complications including 1, 5:
- Cardiac conduction defects
- Diabetes mellitus
- Hearing impairment
- Myopathy
- Gastrointestinal disturbances
Important Considerations
- MELAS is a multisystem disorder requiring a multidisciplinary approach 4, 5
- The A3243G mutation in mitochondrial DNA is the most common cause, present in approximately 80% of patients 1, 3
- Stroke-like episodes typically don't conform to specific arterial territories and preferentially involve the posterior cerebral hemispheres 3, 8
- L-citrulline raises nitric oxide production more than L-arginine but has not been systematically studied in humans with MELAS 1
Pitfalls and Caveats
- No consensus guidelines outlining standard drug regimens exist for MELAS syndrome 4
- Optimal dosage, timing of initiation, and duration of L-arginine therapy remain to be established through randomized controlled trials 1
- The rare nature of MELAS makes generating high-quality evidence for therapies challenging 1
- Treatment response is variable and may require adjustments based on clinical response 5, 8