II. Definitions

  1. Mitochondrial Encephalopathy, Lactic acidosis and Stroke-Like Episodes (MELAS Syndrome)
    1. Inherited mitochondrial disorder that manifests with Seizures, strokes, vascular Headaches, Muscle degeneration and growth failure

III. Epidemiology

  1. Onset in children and young adults
    1. Peak onset age 2 to 10 years old
  2. Incidence: 1 in 4000
  3. Gender: Equally affected

IV. Pathophysiology

  1. Maternally inherited (as with all mitochondrial disorders)
    1. Multiple genetic defects cause MELAS, but a single base pair mutation m.3234>G is found in 80% of cases
  2. Progressive mitochondrial disorder primarily affects nerve and Muscle Tissue (highly metabolically active cells)
    1. tRNA mutations alter respiratory chain complex synthesis
    2. Impaired mitochondrial energy production, resulting in anaerobic activity and Lactic Acidosis
    3. Microvascular angiopathy
    4. Impaired cerebral vasodilation

V. Findings

  1. Recurrent Neurologic Episodes
    1. Encephalopathy
      1. Altered Level of Consciousness with episodes
      2. Longterm gradual deterioration of overall cognitive function
    2. Myopathy
      1. Proximal Muscle Weakness
      2. Exercise intolerance
    3. Migraine Headache
    4. Focal neurologic deficits (stroke-like episodes)
      1. Most commonly presents with Hemiparesis, Hemianopia
      2. Do not follow a typical vascular pattern
      3. Cummulative stroke-like events result in progressive neurologic deficits
      4. MRI demonstrates correlating lesions
    5. Seizures
      1. Focal or Generalized Seizures
      2. Younger age of onset may predispose to treatment refractory Seizures
  2. Other Findings in Children
    1. Growth and development is typically normal until symptom onset and diagnosis
    2. Short Stature is common
    3. Less common onset in infants, may be associated with Failure to Thrive, congenital Deafness

VI. Labs

  1. Lactic Acidosis
  2. Muscle Biopsy: Compensatory mitochondrial proliferation
    1. Ragged Red fibers on Gomori Trichome stain
    2. Perivascular Smooth Muscle reacts to succinate dehydrogenase

VII. Diagnosis

  1. Stroke-Like Events before age 40 years old
  2. Encephalopathy with Seizures and Dementia
  3. Serum Lactic Acidosis
  4. Muscle biopsy with ragged red fibers

VIII. Differential Diagnosis

  1. Kearns-Sayre
    1. Associated with Short Stature, Hearing Loss and Ataxia
    2. Distinguished by its Vision related findings (Ophthalmoplegia, Retinal changes) and cardiac defects
  2. Myoclonus Epilepsy with ragged red fibers (MERRF)
  3. Leigh Syndrome

IX. Associated Conditions

  1. Cardiac Conduction Deficits
  2. Diabetes Mellitus

X. Imaging

  1. MRI Brain
    1. Multifocal infarcts that do not follow typical vascular patterns

XI. Management

  1. No specific MELAS treatments are available
  2. Keep Immunizations updated
    1. Childhood Primary Series
    2. Influenza Vaccine
    3. Pneumococcal Vaccine
  3. Seizure Prophylaxis
    1. Avoid Valproate
  4. Vitamin Supplementation
    1. Coenzyme Q10, Creatine and L-Carnitine
      1. May increase mitochondrial energy production and slow disease
    2. L-Arginine
      1. May decrease symptom attacks and severity
      2. Arginine IV 500 mg/kg in children (10 g/m2 in adults) given within 3 hours of attack
      3. Arginine 150 to 300 mg/kg/day orally divided three times daily for prophylaxis of events
  5. Avoid medications that may provoke disease
    1. Valproate (see Seizures above)
    2. Metformin (risk of Lactic Acidosis)
    3. Dichloroacetate (Peripheral Neuropathy risk)
    4. Mitochondrial toxins
      1. Aminoglycosides
      2. Linezolid
      3. Tobacco
      4. Alcohol

XII. Resources

  1. Pia (2022) MELAS Syndrome, StatPearls, Treasure Island, FL
    1. https://www.ncbi.nlm.nih.gov/books/NBK532959/

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