Current and future medical therapeutic strategies for the functional repair of spinal cord injury

Spinal cord injury (SCI) leads to social and psychological problems in patients and requires costly treatment and care. In recent years, various pharmacological agents have been tested for acute SCI. Large scale, prospective, randomized, controlled clinical trials have failed to demonstrate marked neurological benefit in contrast to their success in the laboratory. Today, the most important problem is ineffectiveness of nonsurgical treatment choices in human SCI that showed neuroprotective effects in animal studies. Recently, attempted cellular therapy and transplantations are promising. A better understanding of the pathophysiology of SCI started in the early 1980s. Research had been looking at neuroprotection in the 1980s and the first half of 1990s and regeneration studies started in the second half of the 1990s. A number of studies on surgical timing suggest that early surgical intervention is safe and feasible, can improve clinical and neurological outcomes and reduce health care costs, and minimize the secondary damage caused by compression of the spinal cord after trauma. This article reviews current evidence for early surgical decompression and nonsurgical treatment options, including pharmacological and cellular therapy, as the treatment choices for SCI.     

急性脊髓损伤MRI影像学评价

目的23例急性脊髓损伤病人在伤后一周内行MRI检查,表现为脊髓受损区T2加权高信号T1加权等或低信号.方法同时对不同损伤程度及不同预后的患者进行比较.脊髓损伤程度、水肿范围、脊髓受压、髓内出血与预后有关,认为MRI检查对判断脊髓损伤程度、指导治疗及判断预后有一定作用.结果认为在脊髓损伤中MRI是一种很有价值的检查手段.通过MRI检查可将脊髓损伤分为两类脊髓受压型和非受压型.T2加权高信号范围大小是估计预后的简便方法,治疗上以脊髓内外联合减压以及防止脊神经进一步损害.结论早期诊断、早期固定牵引及手术是重要的.     

锂剂治疗脊髓损伤机制的研究进展

脊髓损伤是由一系列内外因素所造成的骨科及神经科学领域严重的致残性疾病,是目前医学界的一大难题.锂剂作为治疗双相情感障碍的主要药物已有100多年的历史.研究证实锂剂对脑神经元有保护作用,其对脊髓损伤的治疗作用也渐渐被观察到.锂剂能够通过保护神经元完整、减少损伤后炎症反应、促进神经营养因子的生成和释放、刺激神经发生以及促进自噬、抑制凋亡等机制达到治疗脊髓损伤的目的.通过回顾有关锂剂对神经系统作用的研究,总结分析了锂剂治疗脊髓损伤作用机制的研究进展,以锂剂为基础的综合治疗具有良好的应用前景.     

Somatosensory-evoked potentials in spinal cord injuries

Short-latency somatosensory-evoked potentials after peroneal nerve stimulation were recorded in 25 patients with long-standing incomplete spinal cord injuries. The results were correlated with the patient's ability to walk. Nine patients had normal latencies, and four of these patients had no useful function in their lower limbs. Sixteen patients had prolonged latencies, and eight of these had useful ambulation. It is concluded that the scalp-recorded somatosensory-evoked potentials from peroneal nerve stimulation does not reliably predict function after spinal cord trauma.     

脊柱脊髓损伤合并重型颅脑损伤的早期诊治体会

目的：探讨早期诊治脊柱、脊髓损伤合并重型颅脑损伤病例，降低伤残率、死亡率的有效措施。方法：回顾性分析本院45例患者，及采取的相应诊断治疗措施。结果：临床治愈26例，好转14例，死亡5例。结论：骨科、神经外科和急诊科医生必须给予足够的重视，早期正确检查、及早诊断和有效治疗至关重要，常规行头部和脊柱脊髓影像学检查十分必要，进一步可采取CT三维重建、MRI等检查，提高早期诊断率，对降低伤残与死亡率有着十分重要的临床意义。     

早期手术治疗急性颈脊髓损伤

目的 探讨早期手术治疗急性严重颈脊髓损伤的临床效果。方法 自1999～2002年对24例急性颈脊髓损伤的患者进行早期手术治疗，受伤到手术的平均时间为67h，手术方式包括颈椎前路手术、后路手术及前后路联合手术，对损伤的颈椎节段实施复位、减压、固定和融合。结果 22例获得12．38个月(平均18个月)的随访，除11例全瘫者中的2例无恢复外，其他病例均有不同程度的恢复，ASIA分级平均提高1．8个等级，无并发症发生。结论 对急性严重颈脊髓损伤，早期实施手术治疗可取得满意的治疗效果。     

Adult outcomes for children who sustained firearm-related spinal cord injuries

Objective:To describe the adult functional, participation, education, employment, and quality of life outcomes of children who incurred spinal cord injury (SCI) as the result of gun injuries vs. non-violent etiologies, as well as their utilization of health services.Design:Retrospective-cohort study. Eligibility criteria were current age at least 18 years, at least 5 years after SCI, and injury prior to 19 years of age. After enrolling the gun injury group, we matched individuals with non-violent etiologies from the Midwest Regional SCI Model System database to the gun injury group’s demographic characteristics. Adult outcomes included education level, employment, income, involvement with the criminal justice system, quality of life indicators using PROMIS and SCI-QOL item banks, and utilization of health services.Participants:Twenty-six participants with gun injury SCI matched with 19 participants with non-violent etiologies.Results:Average age at injury was 15 years and current age was 44 years for both cohorts. Individuals from racial minority groups were over-represented in the gun injury cohort. The gun-injury cohort had lower educational attainment. Though employment rates were similar, the gun injury group had a lower income level. Both groups endorsed high average levels of function and quality of life on the PROMIS and SCI-QOL short forms.Conclusions:SCI etiology reflects racial characteristics of the sample and is associated with subsequent educational attainment and income. Rehabilitation planning should consider gun injury etiology in children not as a characteristic that determines a poor outcome, but as a risk factor for reduced educational attainment and lifetime income.     

Surgical management of patients following traumatic spinal cord injury: Identifying barriers to early surgery in a specialized spinal cord injury center

Context/Objective: Early surgery in individuals with traumatic spinal cord injury (T-SCI) can improve neurological recovery and reduce complications, costs and hospitalization. Patient-related and healthcare-related factors could influence surgical delay. This study aimed at determining factors contributing to surgical delay in individuals with T-SCI.

Design: Prospective cohort study.

Setting: Single Level I trauma center in Québec, Canada.

Participants: One hundred and forty-four patients who sustained a T-SCI.

Interventions: None.

Outcome measures: Socio-demographic and clinical administrative data were collected during the pre-operative period. The cohort was stratified in early surgery, or ES (<24 hours post-trauma) and late surgery, or LS (≥ 24 hours post-trauma) groups. A multivariate logistic regression analysis using patient- and healthcare-related factors was carried out to identify the main predictors of LS.

Results: 93 patients had ES (15.6?±?4.7 hours post-trauma), which is 31 hours earlier than the 51 patients in the LS group (46.9?±?30.9 hours; P??3). The transfer delay from trauma site to the SCI center was 8 hours shorter (5.0?±?3.0 hours vs 13.6?±?17.0; P??3) for the ES group, and the surgical plan was completed 17 hours faster (6.0?±?4.0 hours vs 23.3?±?23.6 hours; P??3) than for the LS group. The occurrence of LS was predicted by modifiable factors, such as the transfer delay to the SCI center, the delay before surgical plan completion, and the waiting time for the operating room.

Conclusions: A dedicated team for surgical treatment of individuals with T-SCI, involving direct transfer to the SCI center, faster surgery planning and access to the operating room in hospitals dealing with emergencies from all subspecialties could improve surgical delay and increase the rate of patients undergoing ES.     

中性粒细胞在急性脊髓损伤中作用的实验研究

目的：观察中性粒细胞在脊髓压迫伤中的局部聚集情况及其可能的作用。方法：采用压迫法致大鼠脊髓中度损伤，实验动物分正常大鼠损伤组、低白细胞血症大鼠损伤组和假手术组。观察伤后1、3、6、12、24h伤段脊髓髓过氧化物酶(MPO)活性，记录双下肢运动诱发电位(MEP)，应用斜板试验评价大鼠的运动功能。结果：脊髓压迫伤后1h MPO活性开始升高，3h达到高峰。低白细胞血症组伤后3hMPO活性较对照组明显降低，脊髓运动功能的改善较对照组明显。结论：脊髓损伤后局部中性粒细胞聚集增加，可能参与脊髓继发性损伤。     

Open-heart operations in patients with a spinal cord injury

BACKGROUND: The objective of our study was to evaluate the outcomes of open-heart surgery in patients with a spinal cord injury. METHODS: A retrospective analysis of all patients (n = 8) with a spinal cord injury who underwent open-heart operations in a single institution from April 1994 to November 2006 was conducted. RESULTS: All patients had a permanent spinal cord injury with levels ranging from T3 to L2 with a mean age of 62 years (range, 47-72). Seven coronary artery bypass operations and 2 aortic valve replacements were performed. The mean cardiac ejection fraction was 44% (range, 20-60). Seventy-five percent of the patients were extubated within 24 hours of the operation. A decubitus ulcer occurred in only 1 patient. The acute hospital stay averaged 14 days (range, 6-36). One patient died from multiorgan failure on postoperative day 13 giving an in-hospital 30-day mortality of 12.5%. The 5-year survival was 75% with a mean follow-up of 67 months (range, .5-129). CONCLUSIONS: Open-heart operations in patients with a spinal cord injury can be performed safely with acceptable early and late outcomes.     

Current practices and goals for mean arterial pressure and spinal cord perfusion pressure in acute traumatic spinal cord injury: Defining the gaps in knowledge

Context: The mainstay of treatment for acute traumatic spinal cord injury (SCI) is to artificially elevate the patient’s mean arterial pressure (MAP) to >85 mmHg to increase blood flow to the injured spinal cord for 7 days. However, the literature supporting these recommendations are only Class III evidence. In fact, the critical time window in which to elevate MAP after SCI and the optimal vasopressor to use are largely unknown, as is whether cerebrospinal fluid diversion has a role, and this leads to variability among practitioners. Also undefined is whether manipulating these parameters improves neurological outcome.Objective: Our goal is to better delineate current clinical practice and identify gaps in knowledge surrounding the care of patients with traumatic SCI.Methods: We undertook a systematic review of the current literature identified from PubMed on MAP elevation and spinal cord parenchymal pressure in acute SCI.Results: The 8 articles (6 human; 2 porcine) that met our inclusion criteria were all published within the last 6 years. Four were prospective, 1 was retrospective, and 3 were review articles. Only one study was randomized. All of these studies involved small sample sizes and varying lengths of MAP elevation. Choice of vasopressor was variable as well.Conclusions: From our literature review, we posit that norepinephrine may be the vasopressor of choice, that spinal parenchymal pressure monitors can be safely placed at the injury site, and that the combination of MAP elevation and cerebrospinal fluid drainage may improve neurologic outcome more than either intervention alone.     

Experimental bypass surgery between the spinal cord and caudal nerve roots for spinal cord injuries

Spinal cord injuries often cause permanent neurological deficits and are still considered as inaccessible to efficient therapy. Injured spinal cord axons are unable to spontaneously regenerate in adult mammalians. Re-establishing functional activity especially in the lower limbs by reinnervating the caudal infra-lesional territories could represent an attractive therapeutic strategy. For several years, we have studied and developed surgical bypasses using peripheral nerve grafts bridging the supra-lesional rostral spinal cord to the caudal infra-lesional lumbar roots. Main objectives were: 1- to overcome the spinal cord lesion and the consecutive glial barrier blocking the axonal regeneration; 2- to find and bring an alternative source of regenerating axons; 3- to guide those axons toward precisely definite targets (for example, lower limb muscles). We report here the results of our experimental research, which led us from animal experimental models (rodents, primates) to the first human experimentation. Limitations of the method (especially technical pitfalls) are numerous. However, we have obtained encouraging results in our attempts to "repair" the motor pathway. Functional recovery with strong evidence of centrifugal axonal regeneration from the spinal cord to the periphery has been observed. Regarding the sensory pathway, we have found evidence of centripetal axonal regeneration from the periphery toward the spinal cord. Further studies are obviously advocated, but our experimental model of spinal cord - nerve roots bypasses may be integrated in future "repair" strategies of both motor and sensory pathways following spinal cord injury.     

Mapping the continuum of care to surgery following traumatic spinal cord injury

BackgroundTraumatic spinal cord injury (SCI) is a devastating injury, frequently resulting in paralysis and a lifetime of medical and social problems. Reducing time to surgery may improve patient outcomes. A vital first step to reduce times is to map current pathways of care from injury to surgery, identify rapid care pathways and factors associated with rapid care pathway times.MethodsA retrospective review of the Alfred Trauma Service records was undertaken for all cases of spinal injury recorded in the Alfred Trauma Registry over a three year period. Patients with an Abbreviated Injury Scale (AIS) code matching 148 codes for spinal injury were included in the study. Information extracted from the Alfred Trauma Registry included demographic, clinical and key care timelines.ResultsOf the 342 cases identified, 119 had SCI. The average age of SCI patients was 52 years, with 84% male. The vast majority of SCI patients experienced multiple concurrent injuries (87%). Median time from injury to surgery was 17 h r 28 min for SCI patients in comparison to 28 h r 23 min for non-SCI patients. Three pathways to surgery were identified following Trauma Centre presentation- transfer to surgery direct from trauma unit (median time to surgery was 4 h 17 min.), via Intensive Care (median time to surgery was 24 h 33 min) and via the ward (median time to surgery 28 h r 35 min.) SCI was independently associated with the fastest pathway - direct transfer from trauma unit to surgery - with 41% of SCI cases transferred directly to surgery from the trauma unit.ConclusionNotwithstanding that the vast majority of SCI patients presented with other traumatic injuries, half of all SCI cases reached surgery within 18 h of injury, with 25% within 9 h. SCI was independently associated with direct transfer to surgery from the trauma unit. SCI patients achieve rapid times to surgery within a complex trauma service. Furthermore, the trauma system is well positioned to implement further time reductions to surgery for SCI patients.     

损伤控制骨科在胸腰椎骨折伴脊髓损伤治疗中的应用

随着高速公路及机动车辆的普及,高层建筑的增多,使得创伤发生率有增无减。且致伤因素的动量明显增大,严重创伤和多发伤的比例显著增加,同样合并胸腰椎骨折伴脊髓损伤的严重多发伤也显著增加。自2006年11月至2007年12月救治6例合并胸腰椎骨折伴脊髓损伤患者,采用损伤控制骨科理念指导其相关治疗,效果良好,报告如下。     

17岁以下儿童与少年脊柱脊髓损伤

报告了１７岁以下儿童及少年脊柱脊髓损伤３０例。占同期脊柱骨折、脊髓损伤的６．０６％。主要致伤原因为高处坠落。损伤节段以腰椎为主，多节段脊柱骨折的发生率为４０％。３０例中２６例有神经系统障碍。分析认为：儿童少年脊柱脊髓损伤中多节段脊柱骨折较多；无明显骨折脱位的脊髓损伤较多；保守治疗效果颇佳且病人恢复快，预后良好。     

Continuous intrathecal infusion of baclofen in patients with spasticity caused by spinal cord injuries

The aim of this study was to determine the efficacy and safety of intrathecal baclofen therapy delivered by a programmable pump for the chronic treatment of spinal spasticity. Twelve patients with intractable spasticity caused by spinal cord injuries underwent implantation of a programmable continuous infusion pump after significant reduction in spasticity following an intrathecal test bolus of baclofen. No deaths or new permanent neurological deficits occurred following surgery or chronic intrathecal baclofen therapy. The follow-up (12 months) shows a reduction in rigidity in the lower limb of 2.0 points on the Ashworth scale and in the upper limb of 1.2 points. Muscle spasms were reduced from a mean preoperative score of 2.8 to a mean postoperative score of 1.0. In two cases, we observed postoperative catheter dislocation, a complication which could be corrected surgically. This study demonstrates that chronic intrathecal baclofen infusion is a safe and effective form of treatment of intractable spasticity in patients with spinal cord injury. There is considerable reduction in the risk of infection in view of the fact that interrogation and programming of the implanted programmed pumps is noninvasive. Electronic Publication     

A prospective study on acute spinal injuries

This work examines demographic and clinical characteristics of 163 consecutive cases of acute spinal injuries in a small area of Western Turkey, since 1982. These include all spinal injuries with or without neurological symptoms. Combined conservative and surgical methods were used for treatment. Age, sex, etiology, site of injury, radiologic findings, neurological status, and outcome are compared with the other studies. The results have been found to be parallel to those of the other studies except for some regional differences like an excess of tractor accidents.     

Spinal injuries in the pediatric age group: a review of 82 cases of spinal cord and vertebral column injuries

A review of 82 children with spinal cord and/or vertebral column injury treated in our department between 1968 and 1993 showed that 67% of the patients were boys and the average age was 11.4 years. The cause, vertebral level, and type of injury, and the severity of neurological injury varied with the age of the patient. The cause of pediatric injuries differed from that of adult injuries in that falls were the most common causative factor (56%) followed by vehicular accidents (23%). The most frequent level of spinal injury was in the cervical region (57%, 47 patients) followed by the lumbar region (16.5%, 13 patients). In our series, 18% of the patients had complete injury and the overall mortality rate was 3.6%. Eleven children (13%) had spinal cord injury without radiographic abnormality (SCIWORA), whereas 39 (47%) had evidence of neurological injury. Although the spinal injury patterns differed between children and adolescents, the outcome was found to be predominantly affected by the type of neurological injury (P<0.05). Children with complete myelopathy uniformly remained with severe neurological dysfunction; children with incomplete myelopathy recovered nearly normal neurological function. Finally, the authors conclude that most spinal injuries can be successfuly managed with nonoperative therapy. The literature is reviewed as to the treatment and outcome of pediatric spinal injuries.     

TRH对大鼠脊髓损伤后SCBF和SEP的影响

脊髓损伤（ＳＣＩ）后内源性阿片肽释放，并参与脊髓的继发损伤机制。ＴＲＨ可阻断阿片肽的自主神经效应，而不影响痛觉。本实验探讨大剂量ＴＲＨ（２ｍｇ／ｋｇ／ｈ）治疗对大鼠脊髓打击伤（Ａｌｌｅｎｓ法１０ｇｘ５ｃｍ）后脊髓血流量（ＳＣＢＦ）和脊髓诱发电位（ＳＥＰ）的影响。脊髓损伤后１ｈ，ＳＣＢＦ开始显著下降，持续至伤后２４ｈ，ＳＥＰ峰潜时呈进行性延长趋势；伤后即刻静脉注射ＴＲＨ（２ｍｇ／ｋｇ／ｈ，共５次），可使伤后即刻和２４ｈ的ＳＣＢＦ显著升高，并使伤后ＳＣＢＦ下降时间延迟３ｈ，同时ＳＥＰ峰潜时有不同程度改善。结果表明，ＴＲＨ对受伤脊髓早期有一定的防治作用，并具有一定的后发效应；同时也可促进脊髓的神经传导功能。本文亦对ＴＲＨ治疗ＳＣＩ的病理生物学机制进行了讨论。