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Association between seizure burden and deep grey matter alkalosis following neonatal encephalopathy: possibility for a novel therapy for seizures?

Presented at the Neonatal Society 2016 Summer Meeting.

Uria-Avellanal C1, Price D2, Sokolska M2, Mitra S1, Bainbridge A2, Golay X3, Robertson N1

1 Neonatal Department, UCL Hospital, London, UK
2 Medical Physics and Bioengineering, UCL Hospital, London, UK
3 MR Neurophysics and Translational Neuroscience, UCL Institute of Neurology, London, UK

Background: Neonatal encephalopathy (NE) causes significant morbi-mortality. Phosphorus spectroscopy (31PMRS) provides unique information on brain intracellular pH (pHi) (1). Brain alkalosis has been associated with increased seizure burden in a rodent model (2). The aim of the study is to analyse deep grey matter (DGM) pHi as a realiable biomarker of brain injury in NE following therapeutic hypothermia, and to assess the association between alkalosis and seizure burden.

Methods: Ethical approval and informed consent were obtained. 36 newborn infants who received therapeutic hypothermia were studied. Mean gestational age was 39+5 weeks and birth weight 3393g. They all had an MR scan between 2-15 days of life (median 5). Clinical data, electroencephalographic (background activity and seizure burden in minutes), MRI score (3), thalamic proton MRS (Lactate/N-Acetyl-Aspartate [Lac/NAA] peak-area ratio) and DGM 31PMRS (calculating pHi) were recorded.

Results: 11/36 presented with seizures (0 – 538.7 min). Brain alkalosis was associated with a longer seizure burden (r=0.33, p=0.03) (figure a). There was a statistically significant difference in mean DGM pHi between the group with a favourable (n=30) and unfavourable (n=6) outcome (mean±SD: 7.10 ± 0.11 vs 7.28 ± 0.10 respectively, p<0.001) (figure b). All infants with a Lac/NAA>0.3 –likely to have an unfavourable outcome (4) – had a DGM pHi > 7.15 (7.16 – 7.47), similar to previous findings in whole-brain pHi in non-cooled babies (5).

Association between seizure burden and deep grey matter alkalosis following neonatal encephalopathy: possibility for a novel therapy for seizures?

Conclusion: Brain alkalosis within the first 15 days of life in babies with NE is associated with increased seizure burden in the first 90 hours. Avoiding rebound alkalosis with Na+/H+ exchanger inhibitors could be a new target for treating neonatal seizures in NE and for neuroprotection. Localised brain pHi still predicts outcome following cooling.

Corresponding author: c.uria@ucl.ac.uk

References
1. Moon RB and Richards JH. 1973
2. Helmy MM et al. 2012
3. Barkovich AJ et al. 1998
4. Thayyil S et al. 2010
5. Robertson et al. 1999

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