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IntroductionMechanisms underlying sudden unexpected death in epilepsy (SUDEP) are unclear, but autonomic disorders are thought to play a critical role. However, those dysfunctions have mainly been reported in the peri-ictal context of generalized tonic–clonic seizures. Here, we explored whether heart rate variability (HRV), heart rate (HR), and breathing rate (BR) changes could be observed perictally during focal seizures with or without impaired awareness as well as interictally to assess the risk of SUDEP. We report the case of a 33-year-old patient with drug-resistant bilateral temporal lobe epilepsy who died at home probably from an unwitnessed nocturnal seizure (“probable SUDEP”).MethodsIctal and interictal HRV as well as postictal cardiorespiratory analyses were conducted to assess autonomic functions and overall SUDEP risk. The SUDEP patient was compared to two living male patients from our local database matched for age, sex, and location of the epileptic focus.ResultsInterictal HRV analysis showed that all sleep HRV parameters and most awake HRV parameters of the SUDEP patient were significantly lower than those of our two control subjects with bitemporal lobe epilepsy without SUDEP (p < 0.01). In two focal with impaired awareness seizures (FIAS) of the SUDEP patient, increased postictal mean HR and reduced preictal mean high frequency signals (HF), known markers of increased seizure severity in convulsive seizures, were seen postictally. Furthermore, important autonomic instability and hypersensitivity were seen through fluctuations in LF/HF ratio following two seizures of the SUDEP patient, with a rapid transition between sympathetic and parasympathetic activity. In addition, a combination of severe hypopnea (202 s) and bradycardia (10 s), illustrating autonomic dysfunction, was found after one of the SUDEP patient’s FIAS.DiscussionThe unusual cardiorespiratory and HRV patterns found in this case indicated autonomic abnormalities that were possibly predictive of an increased risk of SUDEP. It will be interesting to perform similar analyses in other SUDEP cases to see whether our findings are anecdotal or instead suggestive of reliable biomarkers of high SUDEP risk in focal epilepsy, in particular focal with or without impaired awareness seizures.

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

Large animal contusion models of spinal cord injury are an essential precursor to developing and evaluating treatment options for human spinal cord injury. Reducing variability in these experiments has been a recent focus as it increases the sensitivity with which treatment effects can be detected while simultaneously decreasing the number of animals required in a study. Here, we conducted a detailed review to explore if head and neck positioning in a cervical contusion model of spinal cord injury could be a factor impacting the biomechanics of a spinal cord injury, and thus, the resulting outcomes. By reviewing existing literature, we found evidence that animal head/neck positioning affects the exposed level of the spinal cord, morphology of the spinal cord, tissue mechanics and as a result the biomechanics of a cervical spinal cord injury. We posited that neck position could be a hidden factor contributing to variability. Our results indicate that neck positioning is an important factor in studying biomechanics, and that reporting these values can improve inter-study consistency and comparability and that further work needs to be done to standardize positioning for cervical spinal cord contusion injury models.