Memory impairment associated with Papez circuit lesions in patients with severe traumatic brain injury assessed by diffuse tensor imaging and volumetric MRI analysis.

Abstract IMPORTANCE: Papez circuit is composed of deep structures of the limbic system which supports episodic memory. Biomechanical modelling suggests that this circuit is particularly exposed to shear forces during traumatic brain injury (TBI). Recent studies showed the relevance of MRIderived measures for improving diagnosis and adapt care of TBI patients. However, the relationship between MRI measures in this specific circuit and memory disorders resulting from TBI remains poorly documented.OBJECTIVE: To relate MRI measurements of the Papez circuit to episodic memory impairment (EMI) in TBI patients, and to assess the relevance of MRI to diagnose EMI consecutive to TBI. DESIGN, SETTING AND PARTICIPANTS: This is a prospective observational study with severe TBI patients enrolled (2006-2012) who did receive neuropsychological assessment and multiparametric brain MRI at distance from the trauma. Patients were classified by neuropsychologist into two groups: those showing an episodic memory impairment (EMI+) and those without impairment (EMI-). We defined an anatomical delineation of the Papez circuit and its sub regions. We extracted MRI measurements in each of these regions and compared statistically between EMI+ and EMI- patients. The same methodology was applied to a control group of 50 healthy controls (HC) to compare with normative values.MAIN OUTCOMES AND MEASURES: Normalized fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were derived from diffusion tensor imaging (DTI) data. The volume of the Papez circuit was extracted from anatomical MRI.RESULTS: Over the study period (2009-2016), 100 patients received an MRI and a neuropsychological assessment 63±22 months after the initial TBI. Patients EMI+ had significantly lower FA and higher MD, RD and AD values than the EMI- and HC in the Papez circuit. Volume measurements showed no difference between EMI+ and EMI-. We also reported abnormalities pattern across sub regions of this circuit between EMI+ and EMI-. The potential of MRI measures in Papez circuit to help diagnosis of EMI in severe TBI patients was confirmed by a multivariate model combining clinical data at baseline and MRI features.CONCLUSIONS AND RELEVANCE: Our study shows a high incidence of damage to the Papez circuit following severe TBI associated with episodic memory impairments. MRI measures of the Papez circuit constitute relevant information for the diagnosis of EMI in severe TBI patients.