Brain glucose metabolism in patients with traumatic brain injury undergoing rehabilitation: a longitudinal 18F-FDG PET study

Valeria Pingue ^1,2* Irene Bossert ¹ Daniela D'Ambrosio ¹ Antonio Nardone ^1,2 Giuseppe Trifirò ¹ Nicola Canessa ³ Diego Franciotta ⁴

• ¹ Scientific Clinical Institute Maugeri (ICS Maugeri), Pavia, Italy
• ² University of Pavia, Pavia, Lombardy, Italy
• ³ University School for Advanced Studies, University Institute of Higher Studies in Pavia, Pavia, Lombardy, Italy
• ⁴ Santa Chiara Hospital, Trento, Trentino-Alto Adige/Südtirol, Italy

Background Measuring 18F-FDG PET-detected brain glucose uptake provides reliable information on metabolic tissue abnormalities, cells dysfunction, and neurovascular changes after traumatic brain injury (TBI).We aimed to study the relationship between post-traumatic brain glucose metabolism and functional outcomes in the so far unexplored field of longitudinally 18F-FDG PET-monitored patients undergoing rehabilitation after moderate-to-severe TBI.Methods Fourteen patients consecutively admitted to our unit in the post-acute phase after TBI underwent 18F-FDG-PET scans performed before and 6 months after inpatient rehabilitation program. The Glasgow Coma Scale (GCS) for neurological status, and the Functional Independence Measure (FIM) plus the Glasgow Outcome Scale-Extended (GOSE) scales for the rehabilitation outcome, were applied on admission and discharge. Voxel-wise analyses were performed, with the Statistical Parametric Mapping (SPM12) software, to investigate pre-vs post-rehabilitation changes of brain metabolism, and their relationships with clinical indices.In the whole sample, 18F-FDG uptake significantly increased in the following five regions that were hypometabolic before rehabilitation: inferior frontal gyrus bilaterally, alongside right precentral gyrus, inferior parietal lobule, and cerebellum. However, only for the right precentral gyrus the median voxel peak-value at baseline resulted a significant predictor of both cognitive (FIM cognitive subscale, p=0.012), and functional (GOS-E, p=0.02; post-vs pre-treatment GOS-E difference, p=0.009) improvements. ROC curve analysis showed that a peak voxel-value of 1.7998 was the optimal cut-off for favourable rehabilitation outcome. Unfavourable functional outcomes were predicted by increased 18F-FDG uptake in the inferior frontal gyrus (GOS-E, p=0.032) and precentral gyrus (FIM cognitive subscale, p=0.017; GOS-E, p=0.015).Conclusions This proof-of-principle study enlightens the metabolic changes occurring in moderateto-severe TBI course. Notably, such changes preferentially involve definite frontal brain areas regardless of TBI localization and entity. These findings pave the way for further studies with translational purposes.