MELAS/Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes

MELAS Syndrome

Information sourced from Genereviews 16-Mar-16 
http://www.ncbi.nlm.nih.gov/books/NBK1233/

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with MELAS, the following evaluations are recommended:

  • Measurement of height and weight to assess growth

  • Audiologic evaluation

  • Ophthalmologic evaluation

  • Assessment of cognitive abilities

  • Physical therapy assessment

  • Neurologic evaluation, MRI, MRS [Kaufmann et al 2004], and, if seizures are suspected, EEG

  • Cardiac evaluation

  • Screening for diabetes mellitus by fasting serum glucose concentration and glucose tolerance test

  • Medical genetics consultation

Treatment of Manifestations

Sensorineural hearing loss has been successfully treated with cochlear implantation [Sue et al 1998Scarpelli et al 2012].

Ptosis can benefit from eyelid "crutches," blepharoplasty, or frontalis muscle-eyelid sling placement.

No therapy is available for PEO or retinopathy.

Aerobic exercise is helpful in MELAS and other mitochondrial diseases [Taivassalo & Haller 2004]. Physical therapy should be implemented in individuals after strokes.

Seizures respond to traditional anticonvulsant therapy.

Standard analgesics can be used for migraine headaches.

Cardiac manifestations can benefit from standard pharmacologic therapy.

Diabetes mellitus can be managed by dietary modification only, especially in thin individuals, or with oral hypoglycemic agents, but often requires insulin therapy.

L-arginine showed promise in treating stroke-like episodes in MELAS [Koga et al 2010].

Prevention of Primary Manifestations

No specific treatment for MELAS exists.

The administration of coenzyme Q10 (CoQ10) (50-100 mg 3x/day) and L-carnitine (1000 mg 3x/day) has been of some benefit to some individuals. In a small randomized double-blind placebo-controlled study, CoQ10 combined with creatine and lipoic acid produced modest benefits including slowing progression of ankle weakness and lower resting plasma lactate concentration [Rodriguez et al 2007].

Idebenone, an analog of CoQ10 that crosses the blood-brain barrier more efficiently, has also been reported as beneficial in anecdotal reports [Napolitano et al 2000]. A clinical trial of idebenone for MELAS is in progress [Author, personal observation].

Prevention of Secondary Complications

Because febrile illnesses may trigger acute exacerbations, individuals with MELAS should receive standard childhood vaccinations, flu vaccine, and pneumococcal vaccine.

Surveillance

Affected individuals and their at-risk relatives should be followed at regular intervals to monitor progression and the appearance of new symptoms. Annual ophthalmologic, cardiologic (electrocardiogram and echocardiogram), and endocrinologic evaluations (fasting blood sugar and TSH) are recommended.

Agents/Circumstances to Avoid

Individuals with MELAS should avoid mitochondrial toxins such as: aminoglycoside antibiotics, linezolid, cigarettes, and alcohol. Valproic acid should be avoided in the treatment of seizures [Lin & Thajeb 2007].

Dichloroacetate (DCA) reduces blood lactate by activating the pyruvate dehydrogenase complex. Anecdotal reports of effectiveness have not been substantiated by a double-blind, placebo-controlled trial, which in fact documented a toxic effect of DCA on peripheral nerves and concluded that individuals with MELAS (who are already at increased risk for peripheral neuropathies) should avoid DCA [Kaufmann et al 2006a].

Evaluation of Relatives at Risk

Molecular genetic testing of at-risk maternal relatives may reveal individuals who have high mutational loads and are thus at risk of developing symptoms. However, no proven disease-modifying intervention exists at present.

See  Genetic Counseling for issues related to testing of at-risk relatives for  genetic counseling purposes.

Pregnancy Management

Infertility may preclude pregnancy in some  affected individuals. Women with MELAS should receive  genetic counseling prior to pregnancy. During pregnancy, affected or at-risk women should be monitored for diabetes mellitus and respiratory insufficiency, which may require therapeutic interventions [Díaz-Lobato et al 2005].

Therapies Under Investigation

Oral administration of L-arginine seems to attenuate the severity of strokes when administered in the acute phase [Koga et al 2005] and to reduce the frequency of strokes when given interictally [Koga et al 2005Koga et al 2010]; double-blind studies are needed to confirm these data.

Beneficial effects of oral succinate were reported in one individual [Oguro et al 2004].

The role of heart transplantation for progressive cardiomyopathy has been reviewed [Bhati et al 2005].

The transfer of nuclear  DNA from fertilized oocytes or zygotes harboring a mtDNA pathogenic variant to a recipient enucleated recipient cells could theoretically prevent transmission of mtDNA diseases and proof of this concept has been demonstrated in pronuclear transfers from abnormally fertilized zygotes that were allowed to under several replications in vitro [Craven et al 2010].

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.