Posters

3

Natural history and clinical associations of plasma interleukin-6 levels in traumatic brain injury

CNS Injury

Leo Layzell

CNS Injury

3

Leo Layzell

Systemic inflammation following traumatic brain injury (TBI) may contribute to its long-term morbidity. However, insufficient knowledge about its natural history and clinical associations limits therapeutic development. In a comprehensive and uniquely multi-modal study, replicating our analysis across 3 independent clinical TBI cohorts, we characterised trajectory of plasma interleukin-6 (IL6, a potent pro-inflammatory cytokine) post-TBI. We further evaluated its associations with fluid and imaging biomarkers and clinical outcomes. We analysed data from multi-centre TBI cohorts totalling >1700 patients: BIO-AX-TBI, CREACTIVE and TRACK-TBI. To determine TBI-specificity of our findings, we used additional data from non-TBI trauma (NTT, total n=122) and non-injured controls (CON, total n=156). Plasma samples were available at acute (≤10 days), subacute (10 days–6 weeks), and chronic (6-/12-months) timepoints. IL6 levels were measured on OLINK (BIO-AX-TBI, CREACTIVE) or MSD S-PLEX (TRACK-TBI). Outcomes included Glasgow Outcome Scale-Extended (GOS-E), MRI lesion volume, fractional anisotropy (FA), and plasma neuronal/astroglial markers. IL6 was acutely elevated post-TBI and NTT, versus CON, highest in TBI. In BIO-AX-TBI, IL6 remained elevated at 6 and 12 months. Higher acute IL6 levels were associated with more intracranial injury extent, extracranial injury, plasma biomarkers of TBI (e.g. NFL, GFAP), and higher resulting lesion volume and white matter injury. Elevated subacute IL6 was associated with unfavourable GOS-E. We show, for the first time, persistent systemic inflammation in a clinical TBI cohort. The relationship between subacute plasma Il6 and outcome suggests that sustained inflammation is particularly detrimental to outcome. Our results motivate and guide future trials of anti-IL6 therapies for TBI.

20

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Diagnostic Uncertainty: A Case of Suspected HSV Encephalitis versus Wernicke’s Encephalopathy

CNS Injury

Monideep Ghosh

22

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Interleukin-6 Signaling in Traumatic Brain Injury and Post-Traumatic Epilepsy

CNS Injury

Anastasia Lubarsky

81

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Long-term Cognitive and Functional Outcomes Following Traumatic Brain Injury in UK Armed Forces Personnel – the ADVANCE Cohort

CNS Injury

Grace Blissitt

CNS Injury

81

Grace Blissitt

Background: Military personnel are at increased risk of traumatic brain injury (TBI). The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) TBI study investigates long-term cognitive and functional outcomes in service-personnel who served in Afghanistan (2003-2014).

Methods: TBI was classified using the Mayo criteria: Symptomatic (symTBI), Mild (mTBI) and Moderate-severe (msTBI), by timing (lifecourse exposure and battlefield injury (~13.7 years post-injury)). Association of TBI across cognitive domains (e.g., executive function, memory, and attention), health-related quality of life (HRQoL ) from EQ-VAS and employment status was assessed.

Results: Of 1019 servicemen, 68% had a history of lifecourse TBI (18.6% symTBI, 36.7% mTBI, 13.0% msTBI). 35.1% were military related and 50.6% civilian. Among the 514 servicemen exposed to major combat trauma, 60% sustained battlefield TBI (15.8% symTBI, 28.1% mTBI, 15.8% msTBI). Battlefield TBI was associated with poorer attention (β=−8.04, p=0.001), delayed memory (β=-3.96, p=0.013), ‘Stroop’ inhibition (β=-4.20, p=0.029), ‘Stroop’ inhibition/switch (β=-5.36, p=0.002) and reaction times (simple: β=31.8ms, p<0.001 and choice: β=32.17ms, p<0.001) compared to uninjured servicemen, with similar associations observed for lifecourse TBI (all p<0.05). Relative to individual full-scale IQ estimates, individuals with msTBI showed a two-fold increased risk of performing outside their expected range across multiple cognitive domains. EQ-VAS was significantly lower in battlefield injury groups relative to uninjured, with the greatest effect in the msTBI group (β=-5.34, p=0.02). Battlefield msTBI was also at greatest risk of unemployment (RR=10.8, p<0.001).

Conclusions: TBI was associated with long-term, multi-domain cognitive impairment, with increased severity linked to greater cognitive dysfunction, reduced HRQoL, and increased unemployment risk.

Abstracts of the posters to be presented at the conference are listed in the following.