Abstracts

Rationale: The Imaging Febrile Status study (IFS) aims to determine feasibility of imaging children within 6 hours of febrile status cessation to identify neuroimaging biomarkers as targets for early intervention to mitigate the development of temporal lobe epilepsy. Acute imaging biomarkers are based on findings from preclinical animal models of febrile status (T2 decreases, T2* reductions) that predict temporal lobe epilepsy and FEBSTAT increased T2 at 72 hours. We present preliminary findings before COVID temporarily suspended study enrollment.

Methods: Children who presented to, or transferred to, Children’s National Hospital Emergency Department or Pediatric ICU were identified, consented, and enrolled by the study team. Children had to meet criteria for febrile status (1 mo-5 years; 30 minutes of continuous seizure; fever > 38.4°F). Where possible children had routine EEG performed, then imaged on a GE Discovery MR750 3T using a 32-channel receive-only head coil with high resolution 3D SPGR, T2, 3D FLAIR CUBE, T2* (main measure), DTI (54 directions), 3D ASL, and MRS within 6 hrs of seizure cessation. We used the patient’s sagittal 3D T1 structural image as input to the Infant FreeSurfer pipeline to generate the skull-stripped brain and automated segmentation of cortical and subcortical brain areas in native space, including hippocampus and amygdala as our regions of interest (ROIs). The hippocampus was then split into 3 sections along the y axis using an in-house MATLAB script for anterior, body, and posterior portions. All other MRI images were co-registered to the T1 image using FSL. Bi-lateral quantitative data were extracted from each imaging sequence and left/right asymmetry ratios measures were created.

Results: Three children met criteria for acute febrile status neuroimaging (Table 1) (5 children met criteria, 1 withdrew, 1 too unstable to image). The primary MRI findings were: (1) Large asymmetric reductions in T2 within the left hippocampus (HF); >6% in anterior HF) and >4% in amygdala (see Table 1). (2) CBF changes: these were variable in HF and consistently lower in the amygdala in the 2 subjects with the largest T2 reductions. (3) MRS demonstrated increased Lac/Cr ratios in one subject with large T2 asymmetry. (4) Finally, multi-echo T2* fitting revealed an increased asymmetry in the HF in all patients, which were largest in those with large CBF reductions and T2 changes.

Conclusions: We successfully scanned children after cessation of febrile status with advanced imaging sequences. In 2 of the 3 subjects, we found considerable alterations in MR metrics in anterior hippocampus and amygdala with decreased T2*, increased T2, decreased CBF in the amygdala, and elevated lactate peaks. Together these findings replicate preclinical animal observations. Importantly, they extend findings from FEBSTAT that imaging abnormalities can be identified immediately following febrile status. Image biomarkers may identify patients who may benefit from acute intervention to prevent temporal lobe epilepsy, a subject of ongoing investigation.

Funding: Please list any funding that was received in support of this abstract.: Supported by NINDS R21NS109669; RO1 NS108296 and NICHD U54 HD090257.