Serum IGF-I Levels Are Associated with Improved White Matter Recovery and Short Term Memory after Traumatic Brain Injury

Presentation Number: OR21-2
Date of Presentation: April 2nd, 2017

Claire Feeney*1, David Sharp2, Peter J Hellyer3, James H Cole2, Gregory Scott2, David Baxter4, Sagar Jilka2, Euan Ross2, Timothy Ham2, Mark Midwinter5 and Anthony P. Goldstone2
1Imperial Centre for Endocrinology, London, 2Imperial College, London, 3C3NL, London, 4Royal Centre for Defence Medicine, Birmingham, 5Academic Section for Musculoskeletal Disease, Leeds


Traumatic brain injury (TBI) is a common disabling condition that can cause long-term cognitive and psychological problems. One of the pathological hallmarks of TBI is diffuse axonal injury and is a key determinant of poor clinical outcome following TBI. There are currently no treatments available to limit axonal recovery or promote its recovery. Diffusion tensor imaging (DTI) is an established imaging technique to measure recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) is a recognised complication of TBI and the GH/IGF-I axis may be implicated in axonal and neuropsychological recovery. GH replacement has been shown to improve cognition and psychological function following TBI and higher serum IGF-I concentrations at baseline have been associated with better neurological and functional outcomes following stroke. However, the effect of IGF-I concentrations on axonal recovery is not well known.

We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. Thirty-nine adults after TBI (84.6% male; age median 30.5y; 87.2% moderate-severe; time since TBI median 16.3 months, n=4 with GHD) were scanned twice, 13.3 months (12.1-14.9) apart, and 35 healthy controls scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n=33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC), and posterior limb of internal capsule (PLIC).

At baseline FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above vs. below the age-related median (IGF-I group x time interaction (F(1,37)=4.62 P=0.038). This remined significant when excluding patients with a longer time since injury and those with less severe injuries. Only the higher IGF-I group had significant improvements in immediate and delayed verbal recall over time significant (IGF‐I group x time interaction (F(1,26)=4.38 P=0.046).

WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. At a mechanistic level this may be due to a neurogenic and/or a neuroprotective effect of IGF-I on axons. These findings suggest that GH/IGF-I system may be a potential therapeutic target following TBI, although more work is needed in this field especially studies investigating the effect of GH replacement on axonal recovery following TBI and other neurodengerative diseases.



Nothing to Disclose: CF, DS, PJH, JHC, GS, DB, SJ, ER, TH, MM, APG