Eagle Shawn R, Puccio Ava M, Agoston Denes V, Soose Ryan, Mancinelli Michael, Nwafo Rachel, McIntyre Peyton, Agnone Allison, Tollefson Savannah, Collins Michael, Kontos Anthony P, Schneider Walter, Okonkwo David O
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Neurotrauma Rep. 2023 Jun 22;4(1):404-409. doi: 10.1089/neur.2023.0003. eCollection 2023.
Chronic consequences of mild traumatic brain injury (mTBI) are heterogeneous, but may be treatable with targeted medical and rehabilitation interventions. A biological signature for the likelihood of response to therapy (i.e., "predictive" biomarkers) would empower personalized medicine post-mTBI. The purpose of this study was to correlate pre-intervention blood biomarker levels and the likelihood of response to targeted interventions for patients with chronic issues attributable to mTBI. Patients with chronic symptoms and/or disorders secondary to mTBI >3 months previous (104 days to 15 years; = 74) were enrolled. Participants completed pre-intervention assessments of symptom burden, comprehensive clinical evaluation, and blood-based biomarker measurements. Multi-domain targeted interventions for specific symptoms and impairments across a 6-month treatment period were prescribed. Participants completed a follow-up testing after the treatment period. An all-possible model's backward logistic regression was built to identify predictors of improvement in relation to blood biomarker levels before intervention. The minimum clinically important difference (MCID) of the change score (post-intervention subtracted from pre-intervention) for the Post-Concussion Symptom Scale (PCSS) to identify treatment responders from non-responders was the primary outcome. The MCID for total PCSS score was 10. The model to predict change in PCSS score over the 6-month intervention was significant ( = 0.09; = 0.01) and identified ubiquitin C-terminal hydrolase L1 (odds ratio [OR] = 2.53; 95% confidence interval [CI], 1.18-5.46; = 0.02) and hyperphosphorylated tau (p-tau; OR = 0.70; 95% CI, 0.51-0.96; = 0.03) as significant predictors of symptom improvement beyond the PCSS MCID. In this cohort of chronic TBI subjects, blood biomarkers before rehabilitation intervention predicted the likelihood of response to targeted therapy for chronic disorders post-TBI.
轻度创伤性脑损伤（mTBI）的慢性后果具有异质性，但可能通过有针对性的医学和康复干预进行治疗。治疗反应可能性的生物学特征（即“预测性”生物标志物）将推动mTBI后的个性化医疗。本研究的目的是将干预前血液生物标志物水平与因mTBI导致慢性问题的患者对靶向干预的反应可能性进行关联。纳入了mTBI发生超过3个月（104天至15年；n = 74）后出现慢性症状和/或疾病的患者。参与者完成了干预前的症状负担评估、全面临床评估和基于血液的生物标志物测量。针对6个月治疗期内的特定症状和损伤进行了多领域靶向干预。治疗期结束后，参与者完成了随访测试。构建了一个全可能模型的向后逻辑回归，以确定与干预前血液生物标志物水平相关的改善预测因素。以脑震荡后症状量表（PCSS）变化分数（干预后减去干预前）的最小临床重要差异（MCID）来区分治疗反应者和无反应者，这是主要结果。PCSS总分的MCID为10。预测6个月干预期间PCSS评分变化的模型具有显著性（F = 0.09；p = 0.01），并确定泛素C末端水解酶L1（优势比[OR] = 2.53；95%置信区间[CI]，1.18 - 5.46；p = 0.02）和高磷酸化tau蛋白（p-tau；OR = 0.70；95% CI，0.51 - 0.96；p = 0.03）是超出PCSS MCID的症状改善的显著预测因素。在这个慢性创伤性脑损伤受试者队列中，康复干预前的血液生物标志物预测了TBI后慢性疾病靶向治疗的反应可能性。
