慢性脊髓压迫减压后的缺血再灌注损伤

目的探讨缺血再灌注损伤是否为慢性脊髓压迫症减压后不明脊髓功能丧失的致伤因素。方法成年新西兰白兔96只,随机分为A组（假手术组）,B组（缺血再灌注组）,C组（慢性压迫减压组）。于0h、0.5h、6h、12h、24h,48h各时间点每组分别取4只动物,检测MDA、CAT、SOD、GSH-Px表达水平;每组于0h及48h时各取4只动物取材行凋亡细胞计数。结果B组MDA、CAT、SOD、GSH-Px于0.5h、6h、12h、24h表达水平明显高于A组;C组MDA、CAT、SOD、GSH-Px于各时间点表达水平均明显高于A组,且C组组间各时间点表达水平无明显区别;C组0h及48h时TUNEL阳性细胞数量无明显差异。结论慢性脊髓压迫减压后减压局部并无明显缺血再灌注损伤标志,缺血再灌注并非减压后脊髓功能丧失的原因。     

Osteoporosis after spinal cord injury.

Dual-photon absorptiometry characterized bone loss in males aged less than 40 years after complete traumatic paraplegic and quadriplegic spinal cord injury. Total bone mass of various regions and bone mineral density (BMD) of the knee were measured in 55 subjects. Three different populations were partitioned into four groups: 10 controls (healthy, age matched); 25 acutely injured (114 days after injury), with 12 reexamined 16 months after injury; and 20 chronic (greater than 5 years after injury). Significant differences (p less than 0.0001) in bone mass mineral between groups at the arms, pelvis, legs, distal femur, and proximal tibia were found, with no differences for the head or trunk. Post hoc analyses indicated no differences between the acutely injured at 16 months and the chronically injured. Paraplegic and quadriplegic subjects were significantly different only at the arms and trunk, but were highly similar at the pelvis and below. In the acutely injured, a slight but statistically insignificant rebound was noted above the pelvis. Regression techniques demonstrated early, rapid, linear (p less than 0.0001) decline of bone below the pelvis. Bone mineral loss occurs throughout the entire skeleton, except the skull. Most bone loss occurs rapidly and below the pelvis. Homeostasis is reached by 16 months at two thirds of original bone mass, near fracture threshold.     

Renal function after acute and chronic spinal cord injury

Computer-assisted renal scintigraphy was performed on 160 acute and 240 chronic spinal cord injury patients, and 287 noninjured controls. Concurrently, measurements of global and individual kidney effective renal plasma flow, time of maximum activity in each kidney, ratio of maximum counts to the counts at 27 minutes after injection over each kidney and number of counts in each kidney at 1 to 2 minutes after injection were made. The time of peak activity over the kidney and differential function at 1 to 2 minutes after injection were not affected significantly by age, sex or spinal cord status. Global and individual effective renal plasma flows were significantly affected by all of these factors. Both plasma flow measures generally were higher for male than for female patients. Effective renal plasma flow decreased steadily after early adulthood and, except for the youngest and oldest patients, values were lower for spinal cord injury patients than for normal controls. The ratio of peak to 27-minute counts was affected significantly by age and spinal cord injury but not by sex. In patients without obvious pathological conditions followup scintigrams 1 to 3 years after injury showed no significant changes owing to interval since injury on any parameter studied. Lower limits of basal scintigraphic parameters are given for evaluation of renal status in neurologically intact or spinal cord injury persons.     

Fibronectin inhibits chronic pain development after spinal cord injury

Chronic pain following spinal cord injury (SCI) is a highly prevalent clinical condition that is difficult to treat. Using both von Frey filaments and radiant infrared heat to assess mechanical allodynia and thermal hyperalgesia, respectively, we have demonstrated that a one-time injection of fibronectin (50?μg/mL) into the spinal dorsal column (1?μL/min each injection for a total of 5?μL) immediately after SCI inhibits the development of mechanical allodynia (but not thermal hyperalgesia) over an 8-month observation period following spinal cord dorsal column crush (DCC). DCC will only induce mechanical Allodynia, but not thermal hyperalgesia or overt motor deficits. By applying various fibronectin fragments as well as competitive inhibitors, these effects were shown to be dependent on the connecting segment-1 (CS-1) motif of fibronectin. Furthermore, we found that acute fibronectin treatment diminished inflammation and blood-spinal cord barrier permeability, which in turn leads to enhanced fiber sparing and sprouting. In particular, the reduction of serotonin (5-HT) in the superficial dorsal horn, an important descending brainstem system in the modulation of pain, was blocked with fibronectin treatment. We conclude that treatment of SCI with fibronectin preserves sensory regulation and prevents the development of chronic allodynia, providing a potential therapeutic intervention to treat chronic pain following SCI.     

Spasticity after spinal cord injury

Symptoms of spasticity are often experienced by individuals with spinal cord injury (SCI) following a period of spinal shock and, in many cases, these symptoms negatively affect quality of life. Despite its prevalence, spasticity as a syndrome in the SCI population is not always managed effectively. This is likely due to the fact that the syndrome can have various presentations, each with their own specific etiology. This overview summarizes the symptoms and pathophysiology of the various presentations of spasticity in the SCI population and discusses the currently accepted management techniques. There is a need for a better understanding of the syndrome of spasticity as well as the development of a valid and reliable assessment tool.     

脊髓损伤后的高凝状态

目的:观察脊髓损伤患者凝血系统的变化。方法:以20例符合条件的脊髓损伤病人为研究对象,分别于伤后2~6h、伤后1、3、5d采集病人股静脉血,测定血浆凝血酶抗凝血酶Ⅲ复合物(TAT)、凝血酶原片段1 2(F1 2)和D-二聚体(D-dimer)浓度;同时测定20名健康献血员TAT、F1 2、D-dimer血浆浓度作为正常对照。结果:正常对照组TAT、F1 2和D-dimer血浆浓度分别为3.1±0.9ng/ml、0.9±0.2nmol/l和42.6±9.3ng/ml。20例脊髓损伤病人伤后2~6hTAT、F1 2、D-dimer血浆浓度即显著增高(P<0.05),分别达45.3±14.2ng/ml、4.1±0.7nmol/l和136.2±14.3ng/ml,伤后1、2d内仍明显高于对照组,伤后3、4d趋于正常。结论:脊髓损伤后可激活凝血系统,造成高凝状态,这种高凝状态于伤后数小时即可发生,且持续存在2~3d。     

Neuronal dysfunction in chronic spinal cord injury

This review describes the changes of spinal neuronal function that occur after a motor complete spinal cord injury (cSCI) in humans. In healthy subjects, polysynaptic spinal reflex (SR) evoked by non-noxious tibial nerve stimulation consists of an early SR component and rarely a late SR component. Soon after a cSCI, SR and locomotor activity are absent. After spinal shock; however, an early SR component re-appears associated with the recovery of locomotor activity in response to appropriate peripheral afferent input. Clinical signs of spasticity take place in the following months, largely as a result of non-neuronal changes. After around 1 year, the locomotor and SR activity undergo fundamental changes, that is, the electromyographic amplitude in the leg muscles during assisted locomotion exhaust rapidly, accompanied by a shift from early to dominant late SR components. The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete spinal cord injury (SCI). At about 1 year after injury, in most cSCI subjects the neuronal dysfunction is fully established and remains more or less stable in the following years. It is assumed that in chronic SCI, the patient's immobility resulting in a reduced input from supraspinal and peripheral sources leads to a predominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and SR generation. Training of spinal interneuronal circuits including the enhancement of an appropriate afferent input might serve as an intervention to prevent neuronal dysfunction after an SCI.     

Urethral hypotonicity after suprasacral spinal cord injury.

Established suprasacral spinal cord injuries usually are associated with detrusor hyperreflexia and varying degrees of detrusor-sphincter dyssynergia. Occasionally, such injuries result in detrusor areflexia or urethral hypotonicity or both. The results of the urodynamic evaluation of 4 patients with suprasacral spinal cord injuries are described. Detrusor areflexia and urethral hypotonicity were demonstrated in 3 cases and urethral smooth muscular hypotonia but preserved reflex detrusor function in 1. It is shown that destruction of the thoracolumbar sympathetic outflow can cause the complete loss of urethral smooth muscular closing function and that resting urethral closure is totally independent of preganglionic cholinergic influences.     

Functional electrical stimulation after spinal cord injury.

This article reviews work mainly from my own laboratory on the effects of electrical stimulation for therapy and function following spinal cord injury. One to two hours per day of intermittent stimulation can increase muscle strength and endurance and also reverse some of the osteoporosis in bones that are stressed by the stimulation. Stimulation during walking can also be used to improve speed and other parameters of the gait. Surface stimulation systems with 1-4 channels of stimulation were used in a multicenter study. Initial increases of almost 20% in walking speed were seen and overall increases of nearly 50% in subjects who continued to receive stimulation for a year on average. Some changes were due to improved strength and coordination with stimulation and additional walking, but a specific effect of stimulation persisted throughout the trial. Improved devices will soon be available commercially that were developed on the basis of feedback from users.     

大鼠脊髓损伤后巢蛋白在脊髓组织中的表达

目的探讨大鼠脊髓损伤后巢蛋白(nestin)的表达规律及其意义。方法30只Wister成年大鼠,随机分为正常对照组(A组)、损伤组(B组)。采用Allen打击模型(25g·cm),在T10段造成急性脊髓损伤,于损伤后1d、3d、1周、4周、8周进行取材,对距离损伤中心5mm处脊髓进行nestin免疫组化检测。应用图像分析软件进行nestin阳性区域面积侧算。结果A组脊髓室管膜细胞只可见极少数细胞胞浆内nestin表达,白质中几乎无表达。B组中nestin于损伤后24h表达于室管膜以及软膜,灰质和白质亦有少量表达,1周达到高峰(P<0.05),4周明显下降,8周时很少或几乎无表达。结论脊髓组织的许多部位可能存在具有分化和更新潜能的祖细胞,脊髓损伤后这些细胞被激活,在功能恢复中可能发挥着重要的作用。     

Activation of spinal GABA receptors attenuates chronic central neuropathic pain after spinal cord injury

In this study, we investigated the role of the spinal GABAergic system in central neuropathic painlike outcomes following spinal cord injury (SCI) produced by a spinal hemitransection at T13 of the rat. After SCI, mechanical allodynia develops bilaterally in both hind paws of the rat, lasting longer than 40 days, as evidenced by an increase in paw withdrawal frequency in response to a weak von Frey filament. In naive rats, intrathecal (i.t.) administration in the lumbar spinal cord of GABAA and GABAB receptor antagonists, bicuculline (1-5 microg) and phaclofen (0.1-5 microg), respectively, causes a dose-dependent increase in the magnitude of mechanical allodynia. The SCI-induced mechanical allodynia in both hind-paws is attenuated by i.t. administration in the lumbar spinal cord of GABAA or GABAB receptor agonists, muscimol (1 microg) or baclofen (0.5 microg), respectively. In electrophysiological experiments, rats with SCI show a bilateral increase in hyperexcitability in response to natural stimuli in wide dynamic range (WDR) neurons in the lumbar spinal dorsal horn. The topical application of muscimol (1 microg) or baclofen (0.5 microg) onto the lumbar cord surface reduce the SCIinduced increased responsiveness of WDR neurons. Inhibitory effects of muscimol and baclofen on both the behavioral mechanical allodynia and the hyperexcitability in WDR neuron with SCI compared to controls, were antagonized by pre-treatment of bicuculline (10 microg) and phaclofen (5 microg), respectively. This study provides behavioral and electrophysiological evidence for the important role of the loss of spinal inhibitory tone, mediated by activation of both GABAA and GABAB receptors, in the development of central neuropathic pain following SCI.     

Megacolon in patients with chronic spinal cord injury

PURPOSE: To investigate the clinical and functional correlates of megacolon in individuals with chronic spinal cord injury (SCI). PATIENTS AND METHODS: This is a cross-sectional study of 128 patients consecutively admitted to a SCI in-patient service in a US Veterans Administration Medical Centre (mean age 57+/-15 years, mean years since injury 20+/-13, 97% male) who underwent plain abdominal radiography for study purposes. Participants were characterised by radiological findings. 'Megacolon' was defined as colonic dilatation of >6 cms in one or more colonic segment(s). Clinical, functional, and medication data were abstracted from the medical and nursing records. Individual interviews were conducted with study participants regarding bowel-related symptoms and treatment over the previous 1-month period. RESULTS: Seventy-three per cent of subjects (n=94) had megacolon, and 52% of these individuals had associated radiological constipation. Subjects with megacolon were compared with those without colonic dilatation (n=34). Factors significantly associated with megacolon were older age, longer duration of injury, symptom of abdominal distension, radiological constipation, urinary outlet surgery, laxative use at least once weekly, use of anticholinergic drugs, and use of calcium-containing antacids. These factors were simultaneously included in a multiple logistic regression model. Independent correlates of megacolon were more than 10 years elapsed since acute injury, age over 50 years, and use of >/=4 laxative doses per month. CONCLUSION: Megacolon is a highly prevalent disorder in individuals with chronic spinal cord injury. Our findings suggest that the presence of megacolon may be predicted in older individuals, and in those who are more than 10 years post-SCI. We also found that clinical constipation was frequently present in individuals with megacolon, despite their significantly greater use of laxatives. SPONSORSHIP: This work was supported by a grant from the Claude D Pepper Geriatric Research and Training Center from the National Institute of Ageing-AG08812-05, and a grant from the Education and Training Foundation of the Paralyzed Veterans Association in the USA. Dr Harari is currently recipient of a grant from Action Research (UK). Spinal Cord (2000) 38, 331 - 339.     

Hypothermia in patients with chronic spinal cord injury

DESIGN: Retrospective analysis of medical records. BACKGROUND/OBJECTIVES: To determine frequency and degree of hypothermic episodes in patients with chronic spinal cord injury (SCI). SETTING: Veterans Administration Medical Center. METHODS: Research involved analysis of body temperature records of 50 chronic patients with tetraplegia. All patients were men with a length of injury of 19 +/- 6 years. Mean age was 53 +/- 15 (SD) years. Data were derived from the computerized patient record database system of the Veterans Administration Medical Center. Results were classified into 3 groups: (a) hypothermia (< 95 degrees F), (b) subnormal temperature (< 97.7 degrees F), and normal temperatures (97.7 degrees F to 98.4 degrees F). Body temperature was recorded during hospitalization (minimum duration of 30 days) using an oral probe twice a day. Ambient temperature was controlled by a central air-conditioning system and maintained at 72 degrees F to 74 degrees F. RESULTS: A total of 867 measurements of body temperature were evaluated; normal temperature was recorded 298 times (35%), subnormal temperature was recorded 544 times (63%), and hypothermia was recorded 25 times (3%). There were 15 patients with 30 hypothermic episodes; subnormal temperature was found in all 50 patients from 1 to 47 times. Regression analysis of age and duration of SCI showed a nonsignificant relationship with body temperature. CONCLUSIONS: Our data suggest that patients with tetraplegia after SCI have significant dysfunction of thermoregulation associated with frequent episodes of subnormal body temperature in a normal ambient environment. Further studies are needed to evaluate possible consequences of low temperatures on the general health of patients and to develop preventive interventions.     

Worklife after traumatic spinal cord injury

OBJECTIVE: To develop predictive models to estimate worklife expectancy after spinal cord injury (SCI). DESIGN: Inception cohort study. SETTING: Model SCI Care Systems throughout the United States. PARTICIPANTS: 20,143 persons enrolled in the National Spinal Cord Injury Statistical Center database since 1973. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Postinjury employment rates and worklife expectancy. RESULTS: Using logistic regression, we found a greater likelihood of being employed in any given year to be significantly associated with younger age, white race, higher education level, being married, having a nonviolent cause of injury, paraplegia, ASIA D injury, longer time postinjury, being employed at injury and during the previous postinjury year, higher general population employment rate, lower level of Social Security Disability Insurance benefits, and calendar years after the passage of the Americans with Disabilities Act. CONCLUSIONS: The likelihood of postinjury employment varies substantially among persons with SCI. Given favorable patient characteristics, worklife should be considerably higher than previous estimates.     

Rehabilitative therapies after spinal cord injury

We review some basic and highly relevant concepts in the effort to develop improved rehabilitative interventions for subjects with spinal cord injury (SCI). Interventions that are likely to contribute to improved sensorimotor function include (1) practice of the specific motor task that needs to be improved; and (2) combining the training with one or more interventions--such as pharmacological modulation of the excitability of spinal neural networks, implantation of selected cell types such as olfactory ensheathing glia (OEG), and/or modulation of the excitability of the spinal cord via epidural stimulation. Upon improvement of the neural control of the musculature following SCI, it will always be prudent to maximize the torque output from these activation patterns by assuring that muscle mass is maintained. Therefore, it seems quite feasible that considerable improvement in locomotor performance can be achieved by improved coordination of motor pools, as well as effective recovery of muscle mass, which will assist in the potential generation of normal forces among agonistic and antagonistic muscle groups.