Progressive encephalopathy in m.3243A > G/MT-TL1 mutation carriers: a quantitative EEG analysis
Anna Scarabello1, Federico Mason2, Lorenzo Ferri3
1DIBINEM Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Objective:
The m.3243A > G/MT-TL1 mutation underlies a broad spectrum of clinical manifestations, varying from the mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome to incomplete phenotypes without stroke-like episodes (SLE), termed MELAS-Spectrum Syndrome (MSS). We systematically analyzed the longitudinal EEG changes in individuals carrying the m.3243A > G/MT-TL1 mutation through visual inspection of paroxysmal abnormalities and quantitative analysis of background activity.
Methods:
Adults with the m.3243A > G/MT-TL1 mutation and at least two EEG recordings during their follow-up were included. For each EEG, we obtained: 1) delta-theta/alpha energy ratio (ER); 2) Higuchi fractal dimension (HD); 3) paroxysmal activities (AR), quantified by two experienced clinicians. A linear mixed model assessed the effect of early SLE phases as a time-dependent covariate.
Results:
Sixteen patients (9 females) were recruited. ER significantly increased over time in temporal-parieto-occipital regions. EEG traces recorded shortly after SLEs showed significantly higher ER, lower HD, and an increasing AR trend.
Conclusions:
Quantitative EEG metrics revealed a gradual disruption of posterior background rhythms in both MSS and MELAS. Early consequences of SLEs include background activity slowing, reduction of brain states complexity, and recrudescence of paroxysmal abnormalities.
Significance:
Neurophysiological signs of progressive brain dysfunction emerged in all individuals with m.3243A > G/MT-TL1 mutation, independently of SLEs.
Insights
The m.3243A>G/MT-TL1 mutation causes progressive brain dysfunction, detectable through EEG changes like altered background rhythms and increased paroxysmal activity, even without stroke-like episodes (SLEs).
Area of Science:
- Neuroscience
- Genetics
- Mitochondrial Diseases
Background:
- The m.3243A>G/MT-TL1 mutation is linked to MELAS syndrome and milder MELAS-Spectrum Syndrome (MSS).
- Longitudinal EEG changes in individuals with this mutation are not fully understood.
Purpose of the Study:
- To systematically analyze longitudinal EEG changes in individuals with the m.3243A>G/MT-TL1 mutation.
- To investigate the impact of stroke-like episodes (SLEs) on EEG patterns.
Main Methods:
- Included adults with m.3243A>G/MT-TL1 mutation and at least two EEG recordings.
- Quantified EEG metrics: delta-theta/alpha energy ratio (ER), Higuchi fractal dimension (HD), and paroxysmal activities (AR).
- Assessed the effect of early SLEs using a linear mixed model.
Main Results:
- EEG energy ratio (ER) significantly increased over time in posterior regions.
- EEG after SLEs showed higher ER, lower HD, and an increasing AR trend.
- Quantitative EEG metrics revealed progressive disruption of posterior background rhythms.
Conclusions:
- Neurophysiological signs of progressive brain dysfunction occur independently of SLEs.
- Early SLE consequences include background slowing, reduced complexity, and increased paroxysmal abnormalities.
- Quantitative EEG analysis offers insights into MELAS and MSS progression.
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