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Cerebrovascular Pressure Reactivity Measures: Index Comparison and Clinical Outcome in Patients With Traumatic Brain Injury Treated According to an Intracranial Pressure-Focused Management: Rejection of the Null Hypothesis. 脑血管压力反应性测量:指数比较与以颅内压为中心的治疗方法治疗脑外伤患者的临床结果:拒绝零假设。
Pub Date : 2023-12-26 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0074
Axel Risinger Liljegren, Camilla Brorsson, Marcus Karlsson, Lars-Owe D Koskinen, Nina Sundström

The aim was to investigate whether the pressure reactivity indices PRx, long-PRx (L-PRx), and pressure reactivity (PR) are interchangeable as measures of vascular reactivity, and whether they correlate with clinical outcome when an intracranial pressure (ICP)-targeted treatment regimen is applied in patients with traumatic brain injury (TBI). Patients with TBI (n = 29) that arrived at the hospital within 24 h of injury were included. PRx and L-PRx were derived from Pearson correlations between mean arterial pressure (MAP) and ICP over a short- and long-time interval. PR was the regression coefficient between the hourly mean values of ICP and MAP. Indices were compared to each other, parameters at admission, and outcome assessed by the extended Glasgow Outcome Scale-Extended (GOSE) at 6 and 12 months. PRx and L-PRx had the strongest correlation with each other (R = 0.536, p < 0.01). A correlation was also noted between L-PRx and PR (R = 0.475, p < 0.01), but not between PRx and PR. A correlation was found between age and PRx (R = 0.482, p = 0.01). No association with outcome for any of the indices was found. PRx/L-PRx and L-PRx/PR were moderately correlated with each other. Age was associated with PRx. None of the indices correlated with outcome when our ICP treatment regime was applied. Part of our null hypothesis, that the three indices are associated with outcome, must be rejected. There was, however, an association between some of the indices. To further understand the relation of treatment regimes and pressure reactivity indices, a larger, randomized study is warranted.

目的是研究压力反应性指数 PRx、长压力反应性(L-PRx)和压力反应性(PR)作为血管反应性的测量指标是否可以互换,以及在对创伤性脑损伤(TBI)患者采用以颅内压(ICP)为目标的治疗方案时,它们是否与临床结果相关。研究对象包括受伤后 24 小时内到达医院的创伤性脑损伤患者(29 人)。PRx和L-PRx来自平均动脉压(MAP)和ICP在短期和长期时间间隔内的皮尔逊相关性。PR 是 ICP 和 MAP 每小时平均值之间的回归系数。各指标之间、入院时的参数之间以及 6 个月和 12 个月后通过格拉斯哥结果量表扩展版(GOSE)评估的结果之间进行了比较。PRx 和 L-PRx 之间的相关性最强(R = 0.536,p R = 0.475,p R = 0.482,p = 0.01)。没有发现任何指数与结果相关。PRx/L-PRx和L-PRx/PR之间呈中度相关。年龄与 PRx 相关。在采用我们的 ICP 治疗方案时,没有一项指标与治疗结果相关。我们的部分零假设,即三个指数与结果相关,必须被拒绝。但是,某些指数之间存在关联。为了进一步了解治疗方案与压力反应指数之间的关系,有必要进行更大规模的随机研究。
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引用次数: 0
Transcutaneous Spinal Cord Stimulation to Stabilize Seated Systolic Blood Pressure in Persons With Chronic Spinal Cord Injury: Protocol Development. 经皮脊髓刺激稳定慢性脊髓损伤患者的坐位收缩压:方案开发。
Pub Date : 2023-12-19 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0063
Caitlyn G Peters, Noam Y Harel, Joseph P Weir, Yu-Kuang Wu, Lynda M Murray, Jorge Chavez, Fiona E Fox, Christopher P Cardozo, Jill M Wecht

Transcutaneous spinal cord stimulation (tSCS) is an emerging therapeutic strategy to target spinal autonomic circuitry to normalize and stabilize blood pressure (BP) in hypotensive persons living with chronic spinal cord injury (SCI). Our aim is to describe our current methodological approach to identify individual tSCS parameters that result in the maintenance of seated systolic blood pressure (SBP) within a pre-defined target range. The parent study is a prospective, randomized clinical trial in which eligible participants will undergo multiple mapping sessions to optimize tSCS parameter settings to promote stable SBP within a target range of 110-120 mm Hg for males and 100-120 mm Hg for females. Parameter mapping includes cathode electrode placement site (T7/8, T9/10, T11/12, and L1/2), stimulation frequency (30, 60 Hz), current amplitudes (0-120 mA), waveform (mono- and biphasic), pulse width (1000 μs), and use of carrier frequency (0, 10 kHz). Each participant will undergo up to 10 mapping sessions involving different electrode placement sites and parameter settings. BP will be continuously monitored throughout each mapping session. Stimulation amplitude (mA) will be increased at intervals of between 2 and 10 mA until one of the following occurs: 1) seated SBP reaches the target range; 2) tSCS intensity reaches 120 mA; or 3) the participant requests to stop. Secondary outcomes recorded include 1) symptoms related to autonomic dysreflexia and orthostatic hypotension, 2) Likert pain scale, and 3) skin appearance after removal of the tSCS electrode. Clinical Trials Registration: NCT05180227.

经皮脊髓刺激(tSCS)是一种新兴的治疗策略,它以脊髓自律神经回路为靶点,使慢性脊髓损伤(SCI)低血压患者的血压恢复正常并保持稳定。我们的目的是介绍我们目前采用的方法,以确定能将坐位收缩压(SBP)维持在预定目标范围内的各个 tSCS 参数。母研究是一项前瞻性随机临床试验,符合条件的参与者将接受多次测绘,以优化 tSCS 参数设置,从而促进 SBP 稳定在男性 110-120 mm Hg、女性 100-120 mm Hg 的目标范围内。参数映射包括阴极电极放置位置(T7/8、T9/10、T11/12 和 L1/2)、刺激频率(30、60 Hz)、电流幅度(0-120 mA)、波形(单相和双相)、脉冲宽度(1000 μs)和载波频率(0、10 kHz)的使用。每位受试者将接受多达 10 次不同电极放置位置和参数设置的映射治疗。每次绘图过程中都将持续监测血压。刺激振幅(毫安)将以 2 到 10 毫安的间隔增加,直到出现以下情况之一:1) 坐位 SBP 达到目标范围;2) tSCS 强度达到 120 mA;或 3) 参与者要求停止。记录的次要结果包括:1)与自主神经反射障碍和直立性低血压有关的症状;2)Likert 疼痛量表;3)移除 tSCS 电极后的皮肤外观。临床试验注册:NCT05180227。
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引用次数: 0
Lifetime Blast Exposure Is Not Related to White Matter Integrity in Service Members and Veterans With and Without Uncomplicated Mild Traumatic Brain Injury. 终生暴露于爆炸环境与患有或未患有轻度脑外伤的军人和退伍军人的白质完整性无关。
Pub Date : 2023-12-14 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0043
Sara M Lippa, Ping-Hong Yeh, Jan E Kennedy, Jason M Bailie, John Ollinger, Tracey A Brickell, Louis M French, Rael T Lange

This study examines the impact of lifetime blast exposure on white matter integrity in service members and veterans (SMVs). Participants were 227 SMVs, including those with a history of mild traumatic brain injury (mTBI; n = 124), orthopedic injury controls (n = 58), and non-injured controls (n = 45), prospectively enrolled in a Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence (TBICoE) study. Participants were divided into three groups based on number of self-reported lifetime blast exposures: none (n = 53); low (i.e., 1-9 blasts; n = 81); and high (i.e., ≥10 blasts; n = 93). All participants underwent diffusion tensor imaging (DTI) at least 11 months post-injury. Tract-of-interest (TOI) analysis was applied to investigate fractional anisotropy and mean, radial, and axial diffusivity (AD) in left and right total cerebral white matter as well as 24 tracts. Benjamini-Hochberg false discovery rate (FDR) correction was used. Regressions investigating blast exposure and mTBI on white matter integrity, controlling for age, revealed that the presence of mTBI history was associated with lower AD in the bilateral superior longitudinal fasciculus and arcuate fasciculus and left cingulum (βs = -0.255 to -0.174; ps < 0.01); however, when non-injured controls were removed from the sample (but orthopedic injury controls remained), these relationships were attenuated and did not survive FDR correction. Regression models were rerun with modified post-traumatic stress disorder (PTSD) diagnosis added as a predictor. After FDR correction, PTSD was not significantly associated with white matter integrity in any of the models. Overall, there was no relationship between white matter integrity and self-reported lifetime blast exposure or PTSD.

本研究探讨了终生暴露于爆炸对军人和退伍军人(SMVs)白质完整性的影响。研究对象是227名SMV,包括有轻度脑外伤(mTBI;n = 124)病史者、骨科损伤对照组(n = 58)和非损伤对照组(n = 45),他们都是国防和退伍军人脑损伤中心(DVBIC)/创伤性脑损伤卓越中心(TBICoE)研究的前瞻性注册对象。根据自我报告的终生接触爆炸次数将参与者分为三组:无(n = 53);低(即 1-9 次爆炸;n = 81);高(即≥10 次爆炸;n = 93)。所有参与者都在伤后至少 11 个月接受了弥散张量成像(DTI)检查。采用兴趣簇(TOI)分析来研究左右脑白质以及 24 个脑簇的分数各向异性以及平均、径向和轴向扩散率(AD)。采用本杰明-霍奇伯格假发现率(FDR)校正。调查爆炸暴露和 mTBI 对白质完整性的回归(控制年龄)显示,存在 mTBI 史与双侧上纵筋束、弓形筋束和左侧脑室的 AD 值较低有关(βs = -0.255 至 -0.174;ps
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引用次数: 0
Firearms Are Now the Leading Cause of Traumatic Brain Injury-Related Mortality in Children. 枪支现在是造成儿童脑外伤相关死亡的主要原因。
Pub Date : 2023-11-23 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0069
Samantha R Neuman, Cordelia Mannix, Rebekah Mannix

Recent studies have demonstrated a significant change in the epidemiology of injury fatalities in children, most notably a marked increase in firearm-related deaths. Few studies have specifically addressed pediatric TBI-related mortality trends. Studying these trends is important for both clinical preparedness and public health interventions. The purpose of this study therefore is to examine recent trends in mechanisms, intents, and rates of pediatric TBI fatalities. Data regarding fatalities from TBI for children <18 years of age from 2011 to 2021 were extracted from the Centers for Disease Control and Prevention, National Center for Health Statistics' web-based injury statistics query and reporting system. We found that firearms became the leading cause of TBI fatalities in children by 2021, most frequently attributable to self-harm. Taken together, the findings from this study underscore the importance in monitoring the changing epidemiology of pediatric TBI fatalities.

最近的研究表明,儿童伤害死亡的流行病学发生了重大变化,最明显的是与枪支相关的死亡人数明显增加。很少有研究专门探讨与小儿创伤性脑损伤相关的死亡率趋势。研究这些趋势对于临床准备和公共卫生干预都非常重要。因此,本研究的目的是探讨儿科创伤性脑损伤致死的机制、意图和比率的最新趋势。有关儿童创伤性脑损伤死亡的数据
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引用次数: 0
Long-Term Functional Outcome and Quality of Life in Long-Term Traumatic Brain Injury Survivors. 脑外伤长期存活者的长期功能结果和生活质量。
Pub Date : 2023-11-22 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0064
Wivi Taalas, Rahul Raj, Juha Öhman, Jari Siironen

Early functional outcome assessments of traumatic brain injury (TBI) survivors may underestimate the long-term consequences of TBI. We assessed long-term temporal changes in functional outcome and quality of life in intensive care unit-managed long-term TBI survivors. This prospective, longitudinal study included 180 patients admitted to a single university hospital during 2000-2002 alive at 15 years post-TBI. Baseline characteristics, including imaging information, were collected. Functional outcome was assessed early (6-24 months) and late (15 years) using the Glasgow Outcome Scale (GOS) and the extended GOS (GOSE). Quality of life was measured at 15 years using the EuroQol Five Dimensions Five Levels (EQ-5D-5L) questionnaire. GOS and GOSE were dichotomized into favorable and unfavorable outcome. An index score was computed for EQ-5D-5L results at 15 years by a standardized valuation protocol. Of 180 patients, 118 replied to 15-year questionnaires. Median age at time of injury was 34 years (interquartile range, 19-45). Using the GCS to assess TBI severity, 67% had a moderate-to-severe TBI. Ninety-seven percent had favorable early functional outcome, and 72% had late favorable functional outcome. Logistic regression found higher age, lower GCS, and Marshall CT III to significantly predict late unfavorable functional outcome. Higher age and Marshall CT III were significant predictors of functional outcome deterioration. Median EQ-5D-5L index score for all patients was 0.88 (0.66-1.00) and correlated positively with GOSE. Most long-term TBI survivors with early favorable outcome also have late favorable functional outcome. Higher age and diffuse brain injury are associated with neurological deterioration. Quality of life was strongly linked to functional outcome.

对创伤性脑损伤(TBI)幸存者的早期功能结果评估可能低估了 TBI 的长期后果。我们对重症监护室管理的长期创伤性脑损伤幸存者的功能结果和生活质量的长期时间变化进行了评估。这项前瞻性纵向研究纳入了 2000-2002 年间在一家大学医院住院的 180 名患者,他们在 TBI 术后 15 年仍健在。研究人员收集了包括影像学信息在内的基线特征。使用格拉斯哥结果量表(GOS)和扩展 GOS(GOSE)对早期(6-24 个月)和晚期(15 年)的功能结果进行了评估。15 年后的生活质量采用 EuroQol Five Dimensions Five Levels (EQ-5D-5L) 问卷进行测量。GOS 和 GOSE 被二分为有利和不利结果。通过标准化评估方案计算出 15 年后 EQ-5D-5L 结果的指数得分。在 180 名患者中,有 118 人回答了 15 年的调查问卷。受伤时的中位年龄为 34 岁(四分位数间距为 19-45 岁)。使用 GCS 评估创伤性脑损伤的严重程度,67% 的患者为中度至重度创伤性脑损伤。97%的患者早期功能恢复良好,72%的患者晚期功能恢复良好。逻辑回归发现,较高的年龄、较低的 GCS 和马歇尔 CT III 可显著预测后期不利的功能预后。较高的年龄和马歇尔 CT III 是功能预后恶化的重要预测因素。所有患者的 EQ-5D-5L 指数中位数为 0.88(0.66-1.00),与 GOSE 呈正相关。大多数早期预后良好的长期创伤性脑损伤幸存者的晚期功能预后也很好。高龄和弥漫性脑损伤与神经功能恶化有关。生活质量与功能预后密切相关。
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引用次数: 0
Long-Term Outcomes Over 20 Years in Persons With Persistent Disorders of Consciousness After Traumatic Brain Injury. 外伤性脑损伤后持续意识障碍患者20年以上的长期预后
Pub Date : 2023-11-21 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0080
Youhei Nakamura, Tadahiko Shiozaki, Hiroshi Ito, Shunichiro Nakao, Hiroshi Ogura, Jun Oda

The long-term outcomes of patients with disorders of consciousness after traumatic brain injury (TBI) is unclear. We investigated the long-term outcomes over 20 years in patients who were in a persistent vegetative state (VS). We conducted a retrospective cohort study using a review of medical records and collected data by telephone and written interviews with patients and their families. We included patients who were treated for TBI at our hospital, between October 1996 and January 2003 and who were in a persistent VS, defined as a Disability Rating Scale (DRS) score of ≥22 at 1 month after TBI. The DRS was administered at 1 month, 6 months, 1 year, and then annually out to 20 years. We evaluated their clinical course until July 2021 with the DRS. We analyzed 35 patients in a persistent VS attributable to TBI. We were able to confirm the 20-year outcomes for 26 of the 35 patients (74%); at 20 years post-TBI, 19 (54%) patients were found to be deceased and 7 (20%) were alive. Over the 20-year study period, 23 of the 35 patients (65.7%) emerged from a persistent VS. Among the 35 patients in a persistent VS at 1 month post-TBI, 20 (57%) emerged from a persistent VS within 1 year, and 3 patients (8.6%) emerged from a persistent VS after more than a year after injury. DRS scores improved up to 9 years post-injury, whereas the change in DRS scores from 10 to 20 years post-injury was within ±1 point in all patients. We found that patients with persistent VS attributable to TBI may show improvement in functional disability up to 10 years post-injury. On the other hand, no substantial improvement in functional disability was observed after the 10th year.

创伤性脑损伤(TBI)后意识障碍患者的长期预后尚不清楚。我们调查了持续植物人状态(VS)患者超过20年的长期结果。我们进行了一项回顾性队列研究,回顾了医疗记录,并通过电话和对患者及其家属的书面采访收集了数据。我们纳入了1996年10月至2003年1月期间在我院接受TBI治疗的持续性VS患者,定义为TBI后1个月残疾评定量表(DRS)评分≥22分。DRS分别在1个月,6个月,1年,然后每年进行一次,直到20年。我们用DRS评估了他们的临床过程,直到2021年7月。我们分析了35例可归因于TBI的持续性VS患者。我们能够确认35例患者中26例(74%)的20年预后;在脑外伤后20年,19例(54%)患者死亡,7例(20%)患者存活。在20年的研究期间,35例患者中有23例(65.7%)出现持续性VS, 35例患者在tbi后1个月出现持续性VS, 20例(57%)在1年内出现持续性VS, 3例(8.6%)在损伤后1年多后出现持续性VS。损伤后9年DRS评分改善,而损伤后10 - 20年DRS评分变化在±1分以内。我们发现,脑外伤引起的持续性VS患者在损伤后10年内可能表现出功能残疾的改善。另一方面,在第10年后,没有观察到功能障碍的实质性改善。
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引用次数: 0
E-Bikes (Electrical Bicycles and Scooters) Related Neurosurgical Injuries in the Adult Population: A Single-Center Experience. 成人中与电动自行车(电动自行车和踏板车)相关的神经外科损伤:单中心经验。
Pub Date : 2023-11-16 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0071
Carla Richetta, Yevgeny Karepov

E-bikes (electrical bicycles and scooters) have been increasingly used as a means of transportation, especially among young adults. E-bikers have more accidents, at higher velocities and more severe kinematics, increasing the rate of neurosurgical injuries. Severe neurosurgical injury patterns result in significant morbidity and mortality. We collected data regarding adult patients (>18 years old), who suffered e-bike-related neurosurgical injuries, in a single tertiary medical center in Israel, between July 2019 and June 2020. Fifty-eight consecutive patients were included in this study. The average age was 34.9, and the average Glasgow Coma Scale (GCS) score upon admission was 13.2 and was significantly lower in operated patients (10.75). Fifty-four patients were riders; 51 (94.5%!) were not wearing a helmet. Fifty percent of patients had multiple types of trauma. Six patients suffered a spinal injury. Sixteen patients required either cranial or spinal surgery. Three patients died, and 1 remained in a vegetative state. Median Glasgow Outcome Scale-Extended (GOS-E) score at follow-up was 7.1. Operated patients stayed significantly longer in the intensive care unit (ICU) and in the hospital, and their GOS-E scores at discharge and follow-up were significantly lower. Most spinal injuries underwent surgery. Patients who wore helmets had significantly higher GCS scores and a shorter stay in the ICU and hospital. The unacceptable reality of the careless use of this transportation and the unique kinematics lead to severe neurosurgical injuries, comorbidities, and even mortality. Our results reflect the risks of e-bikes in the adult population. Most of our patients were in the mid-age group, and almost none had used a helmet. The results of this study highlight the potential need for neurosurgical treatment, and the need for long-term rehabilitation and follow-up, reflecting the emotional and financial toll of these injuries. Once again, this study showed that helmets save lives and emphasized the importance of protecting our heads.

电动自行车(电动自行车和踏板车)已经越来越多地被用作一种交通工具,尤其是在年轻人中。骑电动自行车的人有更多的事故,速度更快,运动更剧烈,增加了神经外科损伤的几率。严重的神经外科损伤模式导致显著的发病率和死亡率。我们收集了2019年7月至2020年6月期间在以色列一个三级医疗中心遭受电动自行车相关神经外科损伤的成年患者(>18岁)的数据。58例连续患者纳入本研究。平均年龄34.9岁,入院时格拉斯哥昏迷评分(GCS)平均为13.2分,手术患者的GCS评分明显低于住院患者(10.75分)。54名患者是骑手;51人(94.5%)未戴安全帽。50%的病人有多种创伤。6名患者出现脊髓损伤。16名患者需要颅脑或脊柱手术。3名患者死亡,1名仍处于植物人状态。随访时格拉斯哥结局扩展量表(GOS-E)评分中位数为7.1。手术患者在重症监护病房(ICU)和医院的住院时间明显延长,出院和随访时GOS-E评分明显降低。大多数脊柱损伤都进行了手术。戴头盔的患者GCS评分明显更高,在ICU和医院的住院时间也更短。不可接受的现实是,不小心使用这种运输和独特的运动学导致严重的神经外科损伤,合并症,甚至死亡。我们的研究结果反映了电动自行车在成年人中的风险。我们的大多数病人都是中年人,几乎没有人戴过头盔。这项研究的结果强调了神经外科治疗的潜在需求,以及长期康复和随访的需求,反映了这些损伤的情感和经济代价。这项研究再次表明,头盔可以挽救生命,并强调了保护我们头部的重要性。
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引用次数: 0
A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO2ST Trial. 研究低氧呼吸对脊髓损伤患者步行功能增强的启动效应的研究方案:BO2ST试验。
Pub Date : 2023-11-06 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0036
William M Muter, Linda Mansson, Christopher Tuthill, Shreya Aalla, Stella Barth, Emily Evans, Kelly McKenzie, Sara Prokup, Chen Yang, Milap Sandhu, W Zev Rymer, Victor R Edgerton, Parag Gad, Gordon S Mitchell, Samuel S Wu, Guogen Shan, Arun Jayaraman, Randy D Trumbower

Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALKtSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALKtSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALKtSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALKtSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALKtSTIM; Placebo + WALKtSTIM; and tAIH + WALKtSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O2 with 60-sec intervals at 21% O2) or daily placebo (fifteen 90-sec episodes at 21% O2 with 60-sec intervals at 21% O2) before a 45-min session of WALKtSTIM or WALKtSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI.

Trial registration: ClinicalTrials.gov, NCT05563103.

短暂的低氧呼吸发作(治疗性急性间歇缺氧;tAIH)可能作为一种有效的可塑性促进引物,以增强慢性(>1年)脊髓损伤(SCI)患者经皮脊髓刺激增强步行治疗(WALKtSTIM)的效果。对脊髓损伤啮齿动物的临床前研究表明,tAIH和WALKtSTIM疗法利用可塑性的互补机制来最大限度地恢复行走。在这里,我们提出了一项多地点临床试验方案,旨在研究tAIH + WALKtSTIM对慢性脊髓损伤患者行走恢复的影响。我们假设每天(8次,2周)tAIH + WALKtSTIM比单独治疗更能促进步行恢复的更快、更持久的改善。为了验证我们的假设,我们正在对60名SCI参与者进行一项安慰剂对照临床试验,他们随机接受三种干预措施之一:tAIH + WALKtSTIM;安慰剂+ WALKtSTIM;和tAIH + WALKtSHAM。参与者在进行45分钟的WALKtSTIM或WALKtSHAM治疗前,每天接受tAIH治疗(15次90秒,10%氧气,间隔60秒,21%氧气)或安慰剂治疗(15次90秒,21%氧气,间隔60秒,21%氧气)。我们的主要结果测量评估步行速度(10米步行测试),耐力(6分钟步行测试)和平衡(计时起来和走测试)。为了安全起见,我们还测量了疼痛水平、痉挛、睡眠行为、认知、全身性高血压和自主神经反射障碍的发生率。评估在治疗前、治疗中、治疗后以及干预后1周、4周和8周进行。本研究的结果扩展了我们对tAIH启动的功能益处的理解,通过研究其增强经皮脊髓刺激对脊髓损伤后恢复行走的神经调节作用的能力。鉴于目前还没有已知的治愈脊髓损伤的方法,也没有单一的治疗方法足以克服行走缺陷,因此迫切需要联合治疗来加速和固定终身脊髓损伤患者的行走能力。试验注册:ClinicalTrials.gov, NCT05563103。
{"title":"A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO<sub>2</sub>ST Trial.","authors":"William M Muter, Linda Mansson, Christopher Tuthill, Shreya Aalla, Stella Barth, Emily Evans, Kelly McKenzie, Sara Prokup, Chen Yang, Milap Sandhu, W Zev Rymer, Victor R Edgerton, Parag Gad, Gordon S Mitchell, Samuel S Wu, Guogen Shan, Arun Jayaraman, Randy D Trumbower","doi":"10.1089/neur.2023.0036","DOIUrl":"https://doi.org/10.1089/neur.2023.0036","url":null,"abstract":"<p><p>Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALK<sub>tSTIM</sub>) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALK<sub>tSTIM</sub> therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALK<sub>tSTIM</sub> on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALK<sub>tSTIM</sub> will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALK<sub>tSTIM</sub>; Placebo + WALK<sub>tSTIM</sub>; and tAIH + WALK<sub>tSHAM</sub>. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O<sub>2</sub> with 60-sec intervals at 21% O<sub>2</sub>) or daily placebo (fifteen 90-sec episodes at 21% O<sub>2</sub> with 60-sec intervals at 21% O<sub>2</sub>) before a 45-min session of WALK<sub>tSTIM</sub> or WALK<sub>tSHAM</sub>. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT05563103.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correlation of Insulin-Like Growth Factor 1 With Cognitive Functions in Mild Traumatic Brain Injury Patients 胰岛素样生长因子1与轻度外伤性脑损伤患者认知功能的相关性
Pub Date : 2023-11-01 DOI: 10.1089/neur.2023.0085
Ju-Chi Ou, Yin-Hsun Feng, Kai-Yun Chen, Yung-Hsiao Chiang, Tsung-I Hsu, Chung-Che Wu
Mild traumatic brain injury (mTBI) is a prevalent health concern with variable recovery trajectories, necessitating reliable prognostic markers. Insulin-like growth factor 1 (IGF-1) emerges as a potential candidate because of its role in cellular growth, repair, and neuroprotection. However, limited studies investigate IGF-1 as a prognostic marker in mTBI patients. This study aimed to explore the correlation of IGF-1 with cognitive functions assessed using the Wisconsin Card Sorting Test (WCST) in mTBI patients. We analyzed data from 295 mTBI and 200 healthy control participants, assessing demographic characteristics, injury causes, and IGF-1 levels. Cognitive functions were evaluated using the WCST. Correlation analyses and regression models were used to investigate the associations between IGF-1 levels, demographic factors, and WCST scores. Significant differences were observed between mTBI and control groups in the proportion of females and average education years. Falls and traffic accidents were identified as the primary causes of mTBI. The mTBI group demonstrated worse cognitive outcomes on the WCST, except for the “Learning to Learn” index. Correlation analyses revealed significant relationships between IGF-1 levels, demographic factors, and specific WCST scores. Regression models demonstrated that IGF-1, age, and education years significantly influenced various WCST scores, suggesting their roles as potential prognostic markers for cognitive outcomes in mTBI patients. We provide valuable insights into the potential correlation of IGF-1 with cognitive functions in mTBI patients, particularly in tasks requiring cognitive flexibility and problem solving.
轻度创伤性脑损伤(mTBI)是一种普遍存在的健康问题,其恢复轨迹多变,需要可靠的预后标志物。胰岛素样生长因子1 (IGF-1)因其在细胞生长、修复和神经保护中的作用而成为潜在的候选者。然而,很少有研究将IGF-1作为mTBI患者的预后指标。本研究旨在探讨IGF-1与mTBI患者认知功能的相关性,采用威斯康星卡片分类测验(WCST)评估。我们分析了295名mTBI参与者和200名健康对照者的数据,评估了人口统计学特征、损伤原因和IGF-1水平。使用WCST评估认知功能。使用相关分析和回归模型来研究IGF-1水平、人口统计学因素和WCST评分之间的关系。mTBI组与对照组在女性比例和平均受教育年限上存在显著差异。跌倒和交通事故被确定为mTBI的主要原因。除了“学会学习”指数外,mTBI组在WCST上表现出更差的认知结果。相关分析显示IGF-1水平、人口统计学因素和特定WCST评分之间存在显著关系。回归模型显示,IGF-1、年龄和受教育年限显著影响各种WCST评分,表明它们是mTBI患者认知结局的潜在预后指标。我们为IGF-1与mTBI患者认知功能的潜在相关性提供了有价值的见解,特别是在需要认知灵活性和解决问题的任务中。
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引用次数: 0
Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) 利用新型工程旋转加速度闭合性脑损伤模型(CHIMERA)表征脑白头雪貂创伤性脑损伤模型
Pub Date : 2023-11-01 DOI: 10.1089/neur.2023.0047
Justin L. Krieg, Anna V. Leonard, Renee J. Tuner, Frances Corrigan
Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets—the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20–1.51 kg; 6–9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n = 4), a 22J (joules) impact (n = 4), or a 27J impact (n = 4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24 h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI.
创伤性脑损伤(TBI)是由机械力作用于大脑引起的,并导致一系列生化反应,进一步损害神经元和支持细胞。临床上,大多数脑损伤是由于对完整颅骨的冲击造成的,这使得闭合性脑损伤临床前模型具有很高的相关性。然而,大多数闭式脑损伤模型使用的是无脑啮齿动物,它们可能不会以与脑回动物相同的方式传递生物力学载荷。为了解决这一翻译空白,本研究旨在表征雪貂(最小的脑回哺乳动物)的急性轴突损伤和小胶质细胞反应。雄性雪貂(Mustela furo;1.20 - -1.51公斤;6-9个月大的婴儿)使用新型的封闭头部损伤模型的工程旋转加速度(CHIMERA)模型。动物被随机分配到假手术组(n = 4)、22J(焦耳)撞击组(n = 4)和27J撞击组(n = 4)。用淀粉样蛋白前体蛋白(APP)、神经丝M (RMO 14.9) (RMO-14)和磷酸化tau (AT180)检测轴突损伤,并在损伤后24小时在灰质和白质区域用离子钙结合接头分子1观察小胶质细胞的反应。在22J脑损伤组中,APP和RMO-14免疫反应性轻度增加,主要发生在胼胝体和穹窿内,而在27J脑损伤组中,更广泛的弥漫性轴索损伤包括丘脑和下丘脑等灰质结构。伴随的小胶质细胞激活仅在27J组中观察到,最明显的是在白质束中对大量轴突损伤做出反应。27J组损伤后脑沟底部的AT180增加,而22J组则没有。这可能表明该菌株可能在该区域最高,表明脑回畸形与无脑畸形大脑的反应不同。雪貂CHIMERA模型能较好地模拟人类闭合性脑损伤的许多组织病理特征,为研究脑损伤的病理生理学提供了一种有前景的模型。
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引用次数: 1
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Neurotrauma reports
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