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Cerebral hyperperfusion and decreased cerebrovascular reactivity correlate with neurologic disease severity in MELAS

L H Rodan1, J Poublanc2, J A Fisher3

  • 1Division of Neurology, Dept. of Pediatrics, Hospital for Sick Children, The University of Toronto, Toronto, ON M5G 1X8, Canada.

Mitochondrion
|March 25, 2015
PubMed
Abstract

Insights

Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome patients show altered cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). These changes correlate with disease severity and mutation load, suggesting potential prognostic markers for stroke-like episodes.

Area of Science:

  • Neurology
  • Mitochondrial Diseases
  • Cerebrovascular Physiology

Background:

  • Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is a maternally inherited disorder.
  • Stroke-like episodes (SLEs) are a hallmark clinical manifestation of MELAS syndrome.
  • The underlying cerebrovascular mechanisms of SLEs in MELAS are not fully understood.

Purpose of the Study:

  • To investigate the mechanisms of stroke-like episodes (SLEs) in MELAS syndrome.
  • To evaluate regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in MELAS patients.
  • To correlate CBF and CVR with disease severity and mitochondrial DNA (mtDNA) mutation load.

Main Methods:

  • A case-control study involving 3 siblings with MELAS syndrome (m.3243A>G tRNA(Leu(UUR))) and variable % mutant mtDNA.
  • 3T MRI with arterial spin labeling (ASL) was used to measure CBF.
  • Cerebrovascular reactivity (CVR) was assessed by measuring the change in Blood Oxygen Level Dependent signal in response to CO2 inhalation.

Main Results:

  • MELAS siblings exhibited significantly decreased CVR and increased CBF compared to healthy controls.
  • CVR and CBF changes correlated inversely and directly, respectively, with disease severity and % mutant mtDNA.
  • Frontal CVR was more reduced, while occipital CBF was more increased in MELAS patients compared to controls.

Conclusions:

  • Disease severity and mutation load in MELAS syndrome are inversely correlated with interictal CVR and directly correlated with frontal CBF.
  • These hemodynamic metrics provide insights into MELAS cerebrovascular pathophysiology.
  • CBF and CVR may serve as noninvasive prognostic markers for stratifying SLEs risk in MELAS patients.
Keywords:
BOLD-fMRICerebral blood flowCerebrovascular reactivityMELAS syndromeMitochondrial disorders

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