What is the management approach for a patient with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) and stroke?

From the Guidelines

Management of a patient with MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) who has experienced a stroke requires a multifaceted approach focusing on both acute stroke management and the underlying mitochondrial disorder. For acute stroke-like episodes, standard stroke protocols should be followed with some modifications. Intravenous L-arginine at 0.5 g/kg over 30-60 minutes is recommended during acute episodes, followed by oral L-arginine at 150-300 mg/kg/day divided into 3 doses for maintenance therapy, as suggested by recent studies 1. Coenzyme Q10 (ubiquinone) should be administered at 5-15 mg/kg/day divided into 2-3 doses. Additional supplements include L-carnitine (1-3 g/day), riboflavin (100-400 mg/day), and creatine monohydrate (5-10 g/day). Seizure management may require anticonvulsants like levetiracetam, which has fewer interactions with mitochondrial function, as noted in guidelines for stroke management 1. Avoid valproic acid as it can worsen mitochondrial dysfunction. Maintain normoglycemia and avoid prolonged fasting by providing regular meals with complex carbohydrates. During illness, implement a "sick day" protocol with increased fluid intake and glucose-containing beverages. Physical and occupational therapy should be initiated early. These interventions target the energy deficit in MELAS by providing alternative energy substrates, improving mitochondrial function, and enhancing nitric oxide production to improve cerebral blood flow, which is particularly important since MELAS stroke-like episodes are not typical ischemic strokes but rather metabolic events resembling strokes, as discussed in the context of mitochondrial disorders and stroke management 1.

Key considerations in the management of MELAS include:

• Early recognition and treatment of stroke-like episodes
• Use of L-arginine and other supplements to improve mitochondrial function and nitric oxide production
• Avoidance of valproic acid and other medications that can worsen mitochondrial dysfunction
• Maintenance of normoglycemia and avoidance of prolonged fasting
• Implementation of a "sick day" protocol during illness
• Initiation of physical and occupational therapy early in the course of treatment.

Overall, the management of MELAS requires a comprehensive approach that addresses both the acute and chronic aspects of the disorder, with a focus on improving mitochondrial function, reducing the frequency and severity of stroke-like episodes, and enhancing overall quality of life, as emphasized in recent guidelines and studies 1.

From the Research

Stroke Management in MELAS Patients

• MELAS syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature 2.
• The most common mutation associated with MELAS syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)) 2.
• Stroke-like episodes in MELAS patients are thought to be caused by mitochondrial angiopathy, or endothelial dysfunction, which can be improved with L-arginine therapy 3, 4.

L-Arginine Therapy

• L-arginine therapy has been shown to improve stroke-like episode symptoms and decrease the frequency and severity of these episodes in MELAS patients 2, 3, 5, 4.
• Oral and intravenous L-arginine administration has been found to be effective in extending the interictal phase, decreasing the incidence and severity of ictuses, and improving symptoms such as headache, nausea/vomiting, impaired consciousness, and visual disturbance 5.
• The maximal plasma arginine concentration was found to be 167 μmol/L when an ictus developed, suggesting a potential therapeutic target for L-arginine therapy 5.

Macroangiopathy in MELAS Patients

• Macroangiopathy is not a rare complication in MELAS patients, with 12 reported cases of MELAS combined with major cerebral arteries abnormalities including stenosis, dissection, occlusion, reversible vasoconstriction, aneurysms, and atherosclerosis 6.
• The correlation between the affected vessels and the lesions in some cases, but not in others, may increase the misdiagnosis rate, highlighting the importance of considering mitochondrial diseases in patients with concurrent macroangiopathic lesions 6.

Treatment Approach

• Management of MELAS syndrome is largely symptomatic and should involve a multidisciplinary team 2.
• In addition to L-arginine therapy, other treatments such as coenzyme Q10, vitamin C, and valproic acid sodium may be used to prevent seizures and improve symptoms 6.
• Further research is needed to determine the optimal treatment approach for MELAS patients with stroke-like episodes and macroangiopathy 3, 6, 5.