MELAS

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Learning objectives

  • A rare cause of stroke
  • Aware of its existence and diagnosis
  • Aetiology and management

Introduction

MELAS is an acronym for Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). It is a disorder of mitochondrial function and oxidative phosphorylation which affects organs with high metabolic needs such as the brain and muscles (myopathy). The end result is ischaemic damage due to presumed transient oxidative phosphorylation dysfunction within the brain parenchyma. Mutations in a particular transfer RNA gene, MT-TL1, cause more than 80 percent of all cases of MELAS. They can occur de novo or be inherited maternally.

Clinical

Onset is often in childhood with muscle weakness and pain. Patients may experience headaches, loss of appetite, vomiting, and seizures due to the lactic acidosis. Most affected individuals experience what are called "stroke-like episodes" usually but not always before age 40. The effect are neurological symptoms such as hemiparesis, coma, myoclonus, ataxia, hemianopia, seizures, and severe headaches resembling migraines.

There is a typically relapsing-remitting course with an accumulation of injury leading to progressive brain damage with progressive disability, weakness, altered vision, cognition. Patients may also have short stature and hearing loss which is sensorineural. Behavioural and psychiatric problems are noted. Schizophrenia has been diagnosed in some patients.

Investigations

  • BloodsU&E,glucose: some develop Type 1/2 Diabetes
  • ECG: a small number have HOCM, WPW and long QT syndromes
  • Venous Blood Gas:Lactic acidosis may not cause a systemic metabolic acidosis
  • Elevated serum lactate:Lactic acid concentrations measured after anaerobic exercise of the forearm.
  • CSF lactate:may be elevated even when serum lactate is normal. Elevated ratio between lactate and pyruvate is high.
  • Skeletal muscle biopsy: classically Ragged red fibres in : morphological, biochemical, and molecular study of the muscle biopsy
  • Genetic testing: identify gene mutations
  • CT/MRI:shows basal ganglia calcification - imaging discussed below

Imaging

  • CT/MRI: Acute infarcts acute infarcts will demonstrate swollen gyri with increased T2 signal. May enhance. Subcortical white matter involved. There may be T2 shine through on DWI with little change on ADC mapping (vasogenic not cytotoxic oedema). Multifocal stroke-like cortical lesions in different stages of evolution crossing the cerebral vascular territories. There is a predilection to the posterior parietal and occipital lobes. There is basal ganglia calcification more prominent feature in older patients.
  • MR spectroscopy:may demonstrate elevated lactate in otherwise normal appearing brain.

Management

Progress is usually inexorable but phenotypes can vary. Coenzyme CoQ10 has been helpful in some patients with MELAS syndrome. L-arginine during the acute episodes may represent a potential new therapy for this syndrome to reduce brain damage due to impaired vasodilation in intracerebral arteries owing to nitric oxide depletion