title: Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome.
abstract: BACKGROUND
  The pathogenesis of stroke-like episodes in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) remains unknown.
  
  
  METHODS
  Fourteen stroke-like episodes in six patients with MELAS were studied using clinical, neuroradiologic, and electrophysiologic approaches. In two patients postmortem examination was done.
  
  
  RESULTS
  Headache and epileptic seizure were the most common presenting symptoms. In 13 of 14 episodes the cerebral cortex was primarily involved with variable subcortical edema particularly in the temporal, occipital, and parietal cortex. Repeated MRI performed in two episodes revealed progressive spread of the cortical lesion to the surrounding cortex for a few weeks after the onset of symptoms. In 6 of 11 episodes T1-weighted hyperintense cortical signal compatible with cortical laminar necrosis was seen during subacute stage of the episode. Fat-suppression MRI confirmed intracortical gyral hemorrhage in one episode. Petechial gyral microhemorrhages were also pathologically confirmed in the autopsy of another patient. In 9 of 11 episodes focal epileptiform discharges on EEG were noted in the acute brain lesion. In seven of nine episodes focal cortical hyperperfusion was seen in SPECT studies.
  
  
  CONCLUSIONS
  The stroke-like episodes in MELAS may reflect neuronal hyperexcitability, which increases energy demand and creates energy imbalance between energy requirement and adequate availability of adenosine triphosphate due to oxidative phosphorylation defect particularly in the susceptible neuronal population, causing cortical necrosis. The episodic nature of stroke-like episodes is unexplained.
authors.affiliation: Department of Medicine, School of Medicine, Kitasato University, Kanagawa, Japan. takahiro@med.kitasato-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Iizuka
authors.forename: F
authors.initials: F
authors.lastname: Sakai
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Hata
authors.forename: S
authors.initials: S
authors.lastname: Tsukahara
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Takiyama
mesh_terms: D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000706:statistics & numerical data