Related Experiment Videos
Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome
1Department of Medicine, School of Medicine, Kitasato University, Kanagawa, Japan. takahiro@med.kitasato-u.ac.jp
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.
Conclusion:
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.
Insights
Stroke-like episodes in MELAS patients may stem from neuronal hyperexcitability and energy imbalance, leading to cortical necrosis. The episodic nature of these events remains unclear.
Area of Science:
- Neurology
- Mitochondrial Diseases
- Neuroimaging
Background:
- The underlying mechanisms of stroke-like episodes in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) are not well understood.
- Investigating these episodes is crucial for understanding MELAS pathogenesis.
Purpose of the Study:
- To investigate the clinical, neuroradiologic, and electrophysiologic characteristics of stroke-like episodes in MELAS patients.
- To explore potential pathogenetic mechanisms contributing to these episodes.
Main Methods:
- Clinical evaluation, neuroimaging (MRI, SPECT), electrophysiologic studies (EEG), and postmortem examination were employed.
- Analysis of 14 stroke-like episodes in 6 MELAS patients.
Main Results:
- Cerebral cortex involvement with edema was common, with lesions spreading over weeks.
- Evidence of cortical laminar necrosis, intracortical gyral hemorrhage, and microhemorrhages was observed.
- EEG showed epileptiform discharges, and SPECT revealed focal cortical hyperperfusion.
Conclusions:
- Stroke-like episodes in MELAS may be linked to neuronal hyperexcitability and an energy imbalance due to oxidative phosphorylation defects, causing cortical necrosis.
- The episodic recurrence of these events requires further investigation.