Neuropeptide depletion in the amygdala in SUDEP: a post mortem study

Objective: Sudden unexpected death in epilepsy (SUDEP) is typically unwitnessed but can be preceded by seizures in the period prior to death. Peri-ictal respiratory dysfunction is a likely mechanism for some SUDEP and central apnoea has been shown following amygdala stimulation. The amygdala is enriched in neuropeptides that modulate neuronal activity and can be transiently depleted following seizures. In a post mortem SUDEP series we sought to investigate alterations of neuropeptidergic networks in the amygdala, including cases with recent poor seizure control. Methods: In 15 SUDEP cases, 12 epilepsy controls and 10 non-epilepsy controls we quantified the labelling index (LI) for galanin, neuropeptide Y (NPY) and somatostatin (SST) in the lateral, basal, accessory basal nuclei and peri-amygdala cortex with whole slide scanning image analysis. Within the SUDEP group, 7 had recent generalised seizures with recovery 24 hours prior to death (SUDEP-R). Results: Galanin, NPY and SST LI were significantly lower in all amygdala regions in SUDEP cases compared to epilepsy controls (p<0.05 to <0.0005) and galanin LI lower in the lateral nucleus compared to non-epilepsy controls (p<0.05). There was no difference in the LI in SUDEP-R group compared to other SUDEP. Higher LI was noted in epilepsy controls than non-epilepsy controls, significant for NPY in lateral and basal nuclei (p<0.005 and p<0.05). Significance: A reduction in galanin in the lateral nucleus in SUDEP could represent acute depletion, relevant to post-ictal amygdala dysfunction. In addition, increased amygdala neuropeptides in epilepsy controls supports their seizure-induced modulation that is relatively deficient in SUDEP; this could represent a vulnerability factor for amygdala dysfunction in the post-ictal period.