Prognostic value of early leukocyte fluctuations for recovery from traumatic spinal cord injury

Abstract

We describe the systemic white blood cell (WBC) response to human spinal cord injury (SCI) and demonstrate how this is influenced by overall trauma severity, lesion level, and neurological grade on admission. We identify acute neutrophilia as a negative predictor for patient outcomes, the occurrence of which reduces the likelihood of American Spinal Injury Association Impairment Scale (AIS) grade conversion. We further show that lymphopenia during the first week of SCI is typically associated with better recovery, but that higher neutrophil to lymphocyte ratios early after SCI are associated with infection presentation in at-risk patients. Collectively, the multi-factorial models described in this work allow for better patient stratification and more accurate prediction of their outcomes.

Peripheral white blood cell responses as emerging biomarkers for patient stratification and prognosis in acute spinal cord injury

“…Any potential use of such changes for SCI prognostication would be both practical and convenient as full blood counts (FBCs) are fast, routinely conducted upon patient admission, and often also measured frequently during the first-week postinjury, at least for critically ill patients. We recently conducted a retrospective study to carefully examine the WBC response to SCI, its relationship to lesion level, overall trauma severity and patient outcomes, and evaluated whether these associations may hold value for prognostication [ 45 ▪▪ ]. Using both an exploration and a validation cohort, we uncovered a strong relationship between significantly elevated neutrophil numbers in the blood of patients with an acute traumatic SCI and the likelihood of little to no functional improvement at hospital discharge, that is, no AIS grade conversion compared to admission data; the odds ratio for an unfavourable outcome in association with acute neutrophilia remained significantly increased after adjusting for age, sex, overall trauma severity, initial AIS grade and infectious complications.…”

“…Intriguingly, however, we did observe that patients presenting with an isolated SCI and clinical lymphopenia during the first 3 days postaccident were more likely to have a substantial improvement in their neurological status (i.e. AIS grade conversion) during their hospital stay [ 45 ▪▪ ]. A further probing of lymphocyte subtypes and function ( vide infra ) is now required to better understand their putative contribution(s) and/or causative involvement in intraspinal inflammation, lesion site development and SCI-IDS.…”

“…Irrespective of these knowledge gaps, receiver-operator characteristics and precision-recall analyses confirmed that, when modelled appropriately, both neutrophilia and lymphopenia can serve as independent prognostic markers of long-term neurological recovery in acute SCI [ 45 ▪▪ ]. These latter findings are consistent with the reports of others that increased neutrophil-to-lymphocyte ratios may be predictive of poor neurological recovery after SCI [ 50 ▪▪ , 51 ].…”

“…That said, a drawback of modern ‘omics’ approaches is that data analysis can be tedious and time-consuming, making them again less suitable at present for patient stratification and selection purposes in early intervention trials. Nevertheless, these methods extend significantly from those used in Jogia et al [ 45 ▪▪ ], in that they allow for a more global understanding of how WBCs respond to and/or are modulated by SCI.…”

Effect of ganglioside combined with Chip Jiaji electro-acupuncture on Nogo-NgR signal pathway in SCI rats

“…Acute spinal cord injury (SCI) is caused by local hemorrhage and edema after violent SCI, leading to apoptosis and necrosis of nerve cells in damaged spinal cord tissue and dysfunction of nervous system function ( Ziegler et al, 2018 , Hills, 2020 , Gong et al, 2020 ). SCI is a serious trauma to the central nervous system, causing serious disability ( Andrade et al, 2021 , Jogia et al, 2021 , Bilchak et al, 2021 ). There is no effective clinical treatment at present ( Yates et al, 2021 , Yoshizaki et al, 2021 ).…”