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Cerebral Mitochondrial Oxidative Metabolism is Closely Related to Electrographic Changes During Recurrent Neonatal Seizures Following Hypoxic-Ischaemic Encephalopathy

Presented at the Neonatal Society 2015 Summer Meeting (programme).

Mitra S1, Bale G2, Mathieson S1, Uria-Avellanal C1, Meek J1, Tachtsidis I2, Robertson NJ1

1 Institute for Women’s Health, University College London, UK
2 Department of Medical Physics and Bioengineering, University College London, UK

Background: Seizures are common after hypoxia-ischaemia (HI) and induce further neuronal damage beyond the underlying pathology. Cytochrome c oxidase (CCO) plays a central role in mitochondrial oxidative metabolism and ATP synthesis. We hypothesized that broadband NIRS measured changes in oxidation status of CCO (Δ[oxCCO]) would correlate with the changes in the electrical activity during neonatal seizures following HIE.

Methods: Ethical approval was obtained (REC reference: 13/LO/0106) and written consent was taken before the study. Recurrent seizures during rewarming (6½ hours after completion of therapeutic hypothermia for 72 hours) in a term infant with severe encephalopathy were studied using a custom-built broadband NIRS system (1), collecting data at 1Hz. Continuous EEG/aEEG data collected over 10 channels and systemic data collected from patient monitor, were synchronized with NIRS data. Mean aEEG was calculated from the mean of the upper and lower values of the aEEG band.

Results: Five electrographic seizures were recorded on the EEG (labelled in the figure as S1 to S5). At the start of each seizure on the aEEG (indicated by a rise in the baseline of the aEEG), the Δ[oxCCO] increased by 3.30 ±1μMol/L. But soon after aEEG activity peaks, the Δ[oxCCO] starts to drop and continues to do so even after the end of each seizure to a progressively lower baseline, which at the end of 90 minutes was -4.19 μMol/L (Figure 1). Δ[HbT] and Δ[HbD] both decreased by 1.51±0.77 μMol/L and 1.50±0.69 μMol/L respectively before the start of each seizure episode, and then returned towards baseline during the seizure. Systemic changes were evident with repetitive seizures. Heart rate and mean arterial blood pressure increased by 5±1.1 beats/min and 5±1.1mm Hg respectively, while peripheral oxygen saturation dropped by 3.2±2.8%during seizures. Rectal temperature fall by 1ºC as cooling was reinstated.

Conclusion: A rapid increase in Δ[oxCCO] at the onset of seizures indicate an increase in mitochondrial energy consumption as the neuronal energy demand increases. Δ[oxCCO] closely correlated with the aEEG changes during seizures. The progressive fall in the Δ[oxCCO] baseline during repeated seizures indicates a continuing depletion of mitochondrial energy state and explain the harmful effects of recurrent seizures.

Corresponding author:

1. Bale G, Mitra S, Meek J, Robertson N, Tachtsidis I. Biomedical optics express. 2014;5(10):3450-66.

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