Morphometric Analysis Core

Specific Aims and Tasks

Morphometrics Core worked with the investigators of the CSR in developing a repository of clinical imaging studies of SUDEP cases enrolled in the Center.  It currently houses over 140 imaging studies from more than 70 SUDEP cases of which the majority (85%) were affected by treatment-resistant epilepsy.

The collection of pre-mortem imaging studies enabled a validation and a follow up on the original study by Mueller et al. Neuroimage Clin 2014;5:208-16 that evaluated structural changes in the brainstem of SUDEP cases with focal epilepsy during the years preceding sudden death. In the follow up study, we found that (i) decreased heart rate variability (HRV) in patients with focal epilepsy correlated with structural volume loss in the brainstem and the area housing brainstem autonomic nuclei explained most of the HRV associated variability and (ii) time to SUDEP negatively correlated with brainstem stem volume loss with autonomic and raphe nuclei showing the most significant variation in the regional volume in relationship to time to SUDEP (Mueller et al. Hum Brain Mapp. 2018 Dec;39(12):4820-4830. PMID: 30096213). These findings are interesting as they suggest that clinical quality imaging may be sufficiently sensitive to detect seemingly progressive structural deterioration in the brainstem nuclei, and this structural change may be an interesting morphological biomarker worth further study in a larger cohort of patients. A subsequent study of investigators of the Core evaluated the Impact of the brainstem atrophy on gray matter connectivity of cortical/subcortical structures and autonomic control and its impact on the modulation of cortical/subcortical functional connectivity. This pilot study of 18 patients with non-lesional focal epilepsy found that impaired brainstem-cortex gray matter connectivity in focal epilepsy seems to negatively affect the brainstem's ability to control cortical activation (Mueller et al. Neuroimage Clin. 2019;23:101888, PMID: 31203171). These findings offer an initial insight at a structure-function relationship and a candidate functional imaging marker with potential relevance to SUDEP.   

                                                               

Figure 1. Imaging Registry of the Morphometrics Core. The registry houses over 140 brain MRI clinical scans of cases enrolled in the CSR. The graph shows the distribution of epilepsy types among the enrolled cases. Of these, 94% of cases with focal epilepsy, 68% of cases with generalized epilepsy, and 78% of cases with unclassified epilepsy were affected by a treatment-resistant epilepsy.  

 

Principal Investigators