Regeneration-based therapies for spinal cord injuries

Although it has been long believed that the damaged central nervous system does not regenerate upon injury, there is an emerging hope for regeneration-based therapy of the damaged central nervous system (CNS) due to the progress of developmental biology and regenerative medicine including stem cell biology. In this review, we have summarized recent studies aimed at the development of regeneration-based therapeutic approaches for spinal cord injuries, including therapy with anti-inflammatory cytokines, transplantation of neural stem/precursor cells and induction of axonal regeneration.     

Missed injuries of the spinal cord.

Damage to the spinal cord had not been recognised initially in 15 patients out of a consecutive series of 353 admitted over a decade to the National Spinal Injuries Centre with paralysis due to trauma to the cord. In some patients the missed diagnosis led to mismanagement and a greater neurological deficit. Missed injuries of the spinal cord are seen in patients with multiple injuries and head injuries and in those without any paralysis. Various radiological errors contribute to the failure to recognise the vertebral injury. In addition to causing severe disability to the victim these missed and mismanaged injuries of the spinal cord cost the National Health Service large sums in compensation. A careful evaluation of the history of each accident, with greater awareness of the potential of certain types of accidents to cause spinal cord injury, should reduce the incidence of missed injuries of the spinal cord.     

Animal models of spinal cord contusion injuries.

BACKGROUND AND PURPOSE: Traumatic spinal cord injury causes initial mechanical disruption of tissue, leading to a complex secondary sequence of pathophysiologic changes and neurologic impairment. These sequelae depend on the impact force delivered to the spinal cord at the time of injury. Successful clinical evaluation of the efficacy of any therapeutic regimen depends on the reliability and reproducibility of an experimental animal model. We describe a trauma device and the biomechanical parameters required to induce severe or moderate spinal cord contusion injury in cats and rats. METHODS: Recovery after injury was determined by behavioral, electrophysiologic, and histologic evaluations. RESULTS: Behavioral and electrophysiologic tests after injury clearly identified the experimental groups. A stable severe paraplegic state (defined as 6 months for cats and 8 weeks for rats), without evidence of behavioral or electrophysiologic recovery, was induced by a 65-Newton (N) load for cats and a 35-N load for rats. Moderate spinal cord contusion injury, from which cats and rats partially recovered after approximately 3 months and 4 weeks, respectively, was induced by a 45- and 25-N load, respectively. CONCLUSION: Use of these injury conditions provides reliable animal models for studies designed to evaluate potential therapeutic regimens for spinal cord injury.     

National survey of spinal injuries in hockey players.

There has been an alarming increase in the number of spinal injuries in hockey players. Between 1976 and 1983, 42 were reported to the Committee on Prevention of Spinal Injuries due to Hockey. The median age of the injured players was 17 years. Of the 42 players 28 had spinal cord injuries, and 17 of them had complete paralysis below the vertebral level of the injury. Strikes from behind and collisions with the boards were common mechanisms of injury. Many of the players had suffered a burst fracture of the cervical spine following a blow to the top of the helmet when the neck was slightly flexed. The committee studied a number of possible etiologic factors and made several recommendations regarding prevention. League officials, coaches, players and equipment manufacturers can all play a role in prevention.     

Cervical spinal cord deformation during simulated head-first impact injuries

The relationship between bony spinal column and spinal cord injury during an injury event is not well understood. While several studies have measured spinal canal occlusion during axial impact, there has been limited work done to quantify the spinal cord compression or deformation during simulated injury. Because the cord is a viscoelastic solid it may provide resistance to bone fragments, ligaments or other elements that move into the canal and impinge it during column injury. This would differentiate the measurement of cord compression from the measurement of occlusion of an empty canal. In the present study, a novel method of visualizing and quantifying spinal cord deformation during dynamic head-first impact of ex vivo human cervical spine specimens (N=6) was developed. A radiodense, biofidelic surrogate spinal cord was imaged in the spinal canal using high speed cineradiography at 1000 frames per second. The dorsal-ventral diameter of the cord was measured at 1.5mm increments along its length for each frame of the radiographic footage. The resulting cord deformations were used to determine the theoretical neurological outcome of the impact based on published in vivo ferret studies. The corresponding probability of recovery for the spinal cord deformations in these tests ranged between 8% for atlantoaxial dislocation injury and 95% for mid-cervical spine hyperextension injury (based on the ferret data). Clinically relevant spinal column fracture patterns were produced in this study.     

Varying physiological response to arm-crank exercise in specific spinal injuries

The purpose of this arm-crank ergometry (ACE) study was to provide a greater understanding of the influence to which specific cervical and thoracic spinal cord injuries contribute to reduction in optimal cardio-respiratory and metabolic function. Twenty five male volunteers aged 20 to 47 years participated. Twenty disabled wheelchair-confined spinal cord injured (SCI) subjects were equally divided into four 'site-specific' groups based on the lesion being within either high- or low- cervical or thoracic anatomical regions. Five physically non-disabled controls (As) were included. Measured variables tended to decrease progressively from As to high-level quadriplegics. Analysis revealed a high variance in maximum cardio-respiratory performance levels between groups (P < 0.001). These findings confirm that limitation to upper body physical capabilities in the SCI during high-intensity ACE is dependent on specific lesion site. Considerable variability in performance levels were measured in those suffering lesions within closely approximating anatomical regions. Results also suggest a greater importance in the location of cervical rather than thoracic injuries in contributing towards higher relative losses in maximal cardio-respiratory and metabolic potential. Alterations in body composition and varying severity of muscle paralysis likely also play a contributing role in reducing optimal metabolic function in SCI individuals. The importance for stringent classification techniques of spinal cord lesion site in predicting upper body physical exercise potential in the SCI has therefore been highlighted in this study.     

Assessing redistribution of muscle innervation zones after spinal cord injuries

This study aimed to examine the redistribution of neuromuscular junctions or innervation zones (IZs) after spinal cord injuries (SCI). Fifteen able-bodied subjects and 15 subjects with SCI (American Spinal Injury Association Impairment Scale A to D), participated in the study. Surface electromyography (EMG) signals were collected from the biceps brachii muscle by a customized linear electrode array when subjects generated maximal isometric voluntary contractions. The Radon transform was applied to detect the IZ locations in the multiple channel surface EMG signals which were differentiated between consecutive channels. The distribution of IZs was compared between the SCI and control groups using the student-t test. Statistical analysis disclosed a significantly wider range of IZs in the SCI group compared with the control group (SCI: 3.83 ± 1.32 IED, control: 2.83 ± 0. 87 IED, IED: inter-electrode distance, p < 0.05). No remarkable shifts of the center of the distribution were observed between the two groups (SCI: 9.23 ± 2.35 IED, control: 8.53 ± 2.33 IED, p = 0.42). Changes of IZ distribution in the paralyzed muscles could be associated with the complex neuromuscular reorganization after the SCI.     

Traumatic injuries of the spinal cord in the cervical segment

A group of 1000 patients treated for traumatic injuries to the spinal cord in cervical segment was analysed. These patients were hospitalized at the Department of Rehabilitation in Konstancin in 1967-1987. The most frequent causes of spine injuries, level and degree of lesions to the spinal cord, techniques of conservative treatment and surgeries and results of therapy are discussed. Significant neurological improvement was observed in 62% of the treated patients. An improvement depended on the degree of lesion to the spinal cord, time and method of therapy, mechanism of trauma, and to some extent patients' age. Finally, hospitalization duration was analysed which greatly depend on the degree of lesions to the spinal cord.     

急性脊髓损伤后大鼠电刺激运动诱发电位的变化

目的：比较不同程度脊髓损伤（SCI）与运动诱发电位（MEP）变化之间的关系,探索MEP检查在SCI早期诊断及预后中的价值。方法：27只雄性SD大鼠以改良Allen‘s打击法致伤T8－T9脊髓,按打击冲量随机分为空白对照组（n=5),SCI A组（50gcf,n=8),SCI B组（70gcf,n=8)和SCI C组（100gcf,n=6),采用单极经皮层电刺激,分别于损伤前、伤后即刻、15min、30min、1h、3h和6h连续观察scMEP变化,并计算脊髓出血坏死区域占脊髓横截面积的比率。结果：对照组MEP无显著改变,SCI A组和SCI B组动物MEP早成份波幅立即减低或消失,以后有所恢复,晚成份波消失后未再出现。SCI C组动物除2只大鼠SCI后MEP仍有所恢复外,其余动物再未出现MEP波。脊髓损伤随打击冲量增大而增加,与伤后1h scMEP最大波幅呈显著相关（r=-0.821)。结论：SCI后scMEP的变化程度与打击冲量和脊髓病理损伤面积相关,提示scMEP可以作为一种脊髓功能检测的客观指标。