Abstracts

Rationale: SUDEP is defined as sudden, unexpected death of someone with known seizures, who was otherwise healthy. SUDEP is the leading cause of death in people with epilepsy and occurs in up to 1 out 1000 adults per year. Autopsy studies do not reveal any other cause than the clinical history of epilepsy. Despite ongoing research both in humans and experimentally, the specific mechanism of SUDEP remains a mystery.  Current hypotheses include respiratory dysfunction, cardiac arrhythmia, postictal generalized electroencephalogram suppression and genetic factors. We postulate the existence of an additional patient population which may illuminate this complex scenario. Methods: We systematically analyzed all adult deaths between 2002 and 2012 that came to the attention of the department of neuropathology at Dalhousie University in Halifax.  Amongst 1367 deceased individuals we identified 34 patients who had no obvious cause for their unexpected death. 26 out of 34 presented with a history of seizures in whom we applied the rigorous SUDEP criteria as published by Annegers et al. 1997 and Nashef et al. 2012.  We evaluated the neuropathological findings in the remaining 8 patients with no seizure history, and applied the hypothesis that clinically undetected structural lesions may have caused seizure spread, resulting in mechanisms similar to those suspected in SUDEP. Results: Out of the 26 patients with a seizure history 13 fulfilled the criteria as possible SUDEP and 13 as definite SUDEP cases according to the criteria of Annegers et al. 1997. 25 of our neuropathological cohort could be classified as definite SUDEP following the criteria by Nashef et al. 2012. The 8 patients with no history of seizures revealed the following neuropathological findings: n= 3 encephalitis; n=3 rhombencephalitis; n=1 diabetic encephalopathy; n=1 ischemic infarct; and n= 1 suspicious traumatic lesions. Conclusions: The analysis of our clinical and autopsy data allowed diagnosing a definite SUDEP in all but 1 patient using the Nashef criteria (in contrast to only half of our patients applying the Annegers criteria).  Of special note is the observation, that 18.3% of all patients with sudden unexpected death (n=34) had no observed seizure activity during lifetime but still revealed neuropathological findings potentially in keeping with a demonstrated epileptogenic focus. We suggest the term SUDDEF for his scenario. Whether some or all of these findings were incidental is undetermined; however we speculate that some patients may have been vulnerable to focal hyperexcitability with seizure spread in critical brain structures such as the brainstem, contributing to sudden death. We propose to integrate these findings into future conceptual considerations of unexpected death including SUDEP. Funding: This project was part of a medical thesis under supervision of Professor Pohlmann-Eden.