The Role of Transcranial Motor Evoked Potentials in Predicting Neurologic and Histopathologic Outcome after Experimental Spinal Cord Ischemia

Background: Monitoring of myogenic motor evoked potentials to transcranial stimulation (tcMEPs) is clinically used to assess motor pathway function during aortic and spinal procedures that carry a risk of spinal cord ischemia (SCI). Although tcMEPs presumably detect SCI before irreversible neuronal deficit occurs, and prolonged reduction of tcMEP signals is thought to be associated with impending spinal cord damage, experimental evidence to support this concept has not been provided. In this study, histopathologic and neurologic outcome was examined in a porcine model of SCI after different durations of intraoperative loss of tcMEP signals.

Methods: In 15 ketamine-sufentanil-anesthetized pigs (weight, 35-45 kg) the spinal cord feeding lumbar arteries were exposed. tcMEP were recorded from the upper and lower limbs. Under normothermic conditions, animals were randomly allocated to undergo short-term tcMEP reduction (group A, < 10 min, n = 5) or prolonged tcMEP reduction (group B, 60 min, n = 10), resulting from temporary or permanent clamping of lumbar segmental arteries. Neurologic function was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated 72 h after induction of SCI.

Results: In all animals except one, segmental artery clamping reduced tcMEP to below 25% of baseline. All but one animal in group A had reduced tcMEP for less than 10 min and had normal motor function and no infarction at 72 h after the initial tcMEP reduction. Seven animals in group B (70%) had reduced tcMEP signals for more than 60 min and were paraplegic with massive spinal cord infarction at 72 h. Two animals (one in both groups) had tcMEP loss for 40 min, with moderate infarction and normal function. In general, histopathologic damage and neurologic dysfunction did not occur when tcMEP amplitude recovered within 10 and 40 min after the initial decline, respectively.     

The Effect of Graded Postischemic Spinal Cord Hypothermia on Neurological Outcome and Histopathology after Transient Spinal Ischemia in Rat

Background: Previous data have shown that postischemic brain hypothermia is protective. The authors evaluated the effect of postischemic spinal hypothermia on neurologic function and spinal histopathologic indices after aortic occlusion in the rat.

Methods: Spinal ischemia was induced by aortic occlusion lasting 10 min. After ischemia, spinal hypothermia was induced using a subcutaneous heat exchanger. Three studies were conducted. In the first study, the intrathecal temperature was decreased to 34, 30, or 27 [degree sign]C for 2 h beginning with initial reperfusion. In the second study, hypothermia (target intrathecal temperature 27 [degree sign]C) was initiated with reflow and maintained for 15 or 120 min. In the third study, the intrathecal temperature was decreased to 27 [degree sign]C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals survived for 2 or 3 days, at which time they were examined and perfusion fixed with 4% paraformaldehyde.

Results: Normothermic ischemia followed by normothermic reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate postischemic hypothermia (27 [degree sign]C for 2 h) resulted in decreasing motor dysfunction. Incomplete protection was noted at 34 [degree sign]C. Fifteen minutes of immediate cooling (27 [degree sign]C) also provided significant protection. Delay of onset of post-reflow hypothermia (27 [degree sign]C) by 5 min or more failed to provide protection. Histopathologic analysis revealed temperature-dependent suppression of spinal neurodegeneration, with no effect of delayed cooling.     

Effects of Cyclosporin A on Neurological Outcome and Serum Biomarkers in the Same Setting of Spinal Cord Ischemia Model

Spinal cord ischemic injury is one of the feared complications during aortic cross-clamping. The aim of this study was to investigate whether cyclosporin A (CsA) has a protective effect on spinal cord during ischemia in a rabbit model. A total of 22 New Zealand white rabbits were studied in three groups. One of the groups served as a sham group (n = 7), in which only laparatomy was performed and closed. One group served as a control group (n = 7), in which rabbits had their abdominal aortas cross-clamped for 40 min following median laparatomy. The last group was the CsA group (n = 8), in which rabbits underwent the same procedure as the control group as well as CsA infusion at 20 mg/(kg · hr) over 60 min starting with aortic cross-clamping and continuing in the first 20 min of reperfusion. Neurological outcome of rabbits was evaluated according to Johnson’s scale at postoperative hours 24 and 48 in all groups, and then they were killed. Their spinal cords were harvested, and segments corresponding to L4-L6 were prepared for pathological examination. Serum neuron-specific enolase (NSE) and nitric oxide (NO) levels were measured prior to and following aortic occlusion, and comparisons were made. Physiological data were similar in all groups. Rabbits in the sham group did not have any neurological deficit. However, all rabbits in the control group showed severe neurological deficits, including total paraplegia in five. According to Johnson’s scale, neurological status of the rabbits at postoperative hour 48 was better in the CsA group compared to controls (p < 0.01). Pathological examination of spinal cord specimens revealed a higher viability index in the CsA group compared to controls (p < 0.01). Serum NSE and NO levels were lower in CsA-treated animals compared to controls. Our results demonstrate that CsA, when administered during ischemia and in the early period of reperfusion, may reduce neuronal damage in the spinal cord in a rabbit model of transient spinal cord ischemia.This study was presented at the Fourth European Association for Cardio-thoracic Surgery/The European Society of Thoracic Surgeons Joint Meeting, Barcelona, Spain, September 24-28, 2005.     

Neuraxial Morphine May Trigger Transient Motor Dysfunction after a Noninjurious Interval of Spinal Cord Ischemia: A Clinical and Experimental Study

Background: A patient underwent repair of a thoracoabdominal aortic aneurysm. Epidural morphine, 4 mg, was given for pain relief. After anesthesia, the patient displayed lower extremity paraparesis. This effect was reversed by naloxone. The authors sought to confirm these observations using a rat spinal ischemia model to define the effects of intrathecal morphine administered at various times after reflow on behavior and spinal histopathology.

Methods: Spinal cord ischemia was induced for 6 min using an intraaortic balloon. Morphine or saline, 30 [mu]g, was injected intrathecally at 0.5, 2, or 24 h after reflow. In a separate group, spinal cord temperature was decreased to 27[degrees]C before ischemia. After ischemia, recovery of motor function was assessed periodically using the motor deficit index (0 = complete recovery; 6 = complete paraplegia).

Results: After ischemia, all rats showed near-complete recovery of function by 4-6 h. Intrathecal injection of morphine at 0.5 or 2 h of reflow (but not at 24 h) but not saline caused a development of hind limb dysfunction and lasted for 4.5 h (motor deficit index score = 4-6). This effect was reversed by intrathecal naloxone (30 [mu]g). Intrathecal morphine administered after hypothermic ischemia was without effect. Histopathological analysis in animals that received intrathecal morphine at 0.5 or 2 h after ischemia (but not at 24 h) revealed dark-staining [alpha] motoneurons and interneurons. Intrathecal saline or spinal hypothermia plus morphine was without effect.     

Transcranial Magnetic Stimulation: Use of Motor Evoked Potentials in the Evaluation of Surgically Induced Spinal Cord Ischemia

Abstract

We evaluated transcranial magnetic stimulation producing motor evoked potentials (TMS MEP) as a method to detect spinal cord ischemia during surgery for thoracoabdominal aneurysms. Four groups of swine were subjected to different types of surgically-induced ischemia. TMS MEP and neurological function were assessed at baseline, immediately after the ischemic insult and after four hours of reperfusion/post-ligation. Cross-clamping of the aorta in groups A & B resulted in the disappearance and subsequent reappearance of TMS MEP with significantly prolonged latencies in most animals and variable neurological function. Ligation of intercostal arteries produced no changes in TMS MEP or neurological function (group C). However, after ligation of intercostal and lumbar arteries, group D demonstrated no reappearance of TMS MEP and severe neurological deficits. TMS MEP can provide rapid detection of global spinal cord ischemia and can also predict local devascularization injury. (J Spinal Cord Med 1997; 20:395-401)     

Reliability and Repeatability of the Motor and Sensory Examination of the International Standards for Neurological Classification of Spinal Cord Injury

Abstract

Objective: To determine the reliability and repeatability of the motor and sensory examination of the International Standards for Classification of Spinal Cord Injury (SCI) in trained examiners.

Participants/Methods: Sixteen examiners (8 physicians, 8 physical therapists) with clinical SCI experience and 16 patients participated in a reliability study in preparation for a clinical trial involving individuals with acute SCI. After a training session on the standards, each examiner evaluated 3 patients for motor, light touch (LT), and pin prick (PP). The following day, 15 examiners reevaluated one patient. Interrater reliability was determined using intraclass correlation coefficients (1-way, random effects model). Intrarater reliability was determined using a 2-way random effects model. Repeatability was determined using the method of Bland and Altman.

Results: Patients were classified as complete tetraplegia (n = 5), incomplete tetraplegia (n = 5), complete paraplegia (n = 5), and incomplete paraplegia (n = 1). Overall, inter-rater reliability was high: motor = 0.97, LT = 0.96, PP = 0.88. Repeatability values were small in patients with complete SCI (motor < 2 points, sensory < 7 points) but large for patients with incomplete SCI. Intra-rater reliability values were > 0.98 for patients with complete SCI.

Conclusions: The summed scores for motor, LT, and PP in subjects with complete SCI have high interrater reliability and small repeatability values. These measures are appropriately reliable for use in clinical trials involving serial neurological examinations with multiple examiners. Further research in subjects with incomplete SCI is needed to determine whether repeatability is acceptably small.     

The International Standards for Neurological Classification of Spinal Cord Injury: Intra-Rater Agreement of Total Motor and Sensory Scores in the Pediatric Population

Background: The International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI) is the gold standard for evaluating and classifying the neurological consequence of spinal cord injury (SCI). Objective: To determine the within-rater agreement for total scores of light touch (LT), pin prick (PP), and total motor (TM) in children and youth.

Design: Part of a larger cross-sectional study to determine the intra-rater reliability of the standards when applied to children and youth.

Participants/Methods: A total of 187 subjects participated in 2 repeated examinations performed by the same rater. A total of 7 raters participated in this study. Intraclass correlations coefficients (ICCs), with 95% Cl were calculated to determine agreement between the 2 examinations for LT, PP, and TM.

Results: With the exception of subjects younger than 6 years, agreement on repeated total PP, LT, and TM scores were good to excellent, as shown by ICC values of 0.92 or higher. Although agreement was high for the youngest age group for LT (ICC = 0.920), PP (ICC = 0.957), and TM (ICC = 0.971), all of the lower 95% Cl values fell well below 0.66, indicating poor precision. All subgroups had good to high agreement for total PP, LT, and TM scores, as indicated by ICC values of 0.87 and higher. There were lower 95% Cl (LCI) values for the 6- to 11-year-old group with incomplete paraplegia due to the low number of subjects in that subgroup (N = 4). The LCI values were poor for PP for the subgroups with 6- to 11-year-olds with incomplete tetraplegia (LCI = 0.675) and the 12- to 15-year-old group with incomplete paraplegia (LCI = 0.707) and for TM for 16- to 21-year-old group with complete paraplegia (LCI = 0.706).

Conclusions: In children as young as 6 years, within-rater agreement on LT, PP, and TM exceeded recommended values for clinical measures. With the exception of 6- to 11-year-olds with incomplete injuries, type of injury and severity of injury were not factors in agreement. Although more work is needed to define the lower age limit in which the ISCSCI have utility, these data represent growing evidence supporting the use of the ISCSCI when evaluating the neurological consequence of SCI in children.     

The International Standards for Neurological Classification of Spinal Cord Injury: Intra-Rater Agreement of Total Motor and Sensory Scores in the Pediatric Population

Background:

The International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI) is the gold standard for evaluating and classifying the neurological consequence of spinal cord injury (SCI).

Objective:

To determine the within-rater agreement for total scores of light touch (LT), pin prick (PP), and total motor (TM) in children and youth.

Design:

Part of a larger cross-sectional study to determine the intra-rater reliability of the standards when applied to children and youth.

Participants/Methods:

A total of 187 subjects participated in 2 repeated examinations performed by the same rater. A total of 7 raters participated in this study. Intraclass correlations coefficients (ICCs), with 95% CI were calculated to determine agreement between the 2 examinations for LT, PP, and TM.

Results:

With the exception of subjects younger than 6 years, agreement on repeated total PP, LT, and TM scores were good to excellent, as shown by ICC values of 0.92 or higher. Although agreement was high for the youngest age group for LT (ICC = 0.920), PP (ICC = 0.957), and TM (ICC = 0.971), all of the lower 95% CI values fell well below 0.66, indicating poor precision. All subgroups had good to high agreement for total PP, LT, and TM scores, as indicated by ICC values of 0.87 and higher. There were lower 95% CI (LCI) values for the 6- to 11-year-old group with incomplete paraplegia due to the low number of subjects in that subgroup (N = 4). The LCI values were poor for PP for the subgroups with 6- to 11-year-olds with incomplete tetraplegia (LCI = 0.675) and the 12- to 15-year-old group with incomplete paraplegia (LCI = 0.707) and for TM for 16- to 21-year-old group with complete paraplegia (LCI = 0.706).

Conclusions:

In children as young as 6 years, within-rater agreement on LT, PP, and TM exceeded recommended values for clinical measures. With the exception of 6- to 11-year-olds with incomplete injuries, type of injury and severity of injury were not factors in agreement. Although more work is needed to define the lower age limit in which the ISCSCI have utility, these data represent growing evidence supporting the use of the ISCSCI when evaluating the neurological consequence of SCI in children.     

Neuroprotective Effects of Riluzole and Ketamine during Transient Spinal Cord Ischemia in the Rabbit

Background: Massive release of central excitatory neurotransmitters is an important initial step in ischemic neuronal injury, and modification of this process may provide neuroprotection. We studied the protective effects of the voltage-dependent sodium channel antagonist riluzole and the N-methyl-d-aspartate receptor antagonist ketamine on hind limb motor function and histopathologic outcome in an experimental model of spinal cord ischemia.

Methods: Temporary spinal cord ischemia was induced by 29 min of infrarenal balloon occlusion of the aorta in 60 anesthetized New Zealand white rabbits. Animals were randomly assigned to one of four treatment groups (n = 15 each): group C, saline (control); group R, riluzole, 8 mg/kg intravenously; group K, ketamine, 55 mg/kg intravenously; group RK, riluzole and ketamine. After reperfusion, riluzole treatment was continued with intraperitoneal infusions. Normothermia (38[degrees]C) was maintained during ischemia, and rectal temperature was assessed before and after intraperitoneal infusions. Neurologic function, according to Tarlov's criteria, was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated after 72 h.

Results: Neurologic outcome was better in groups R and RK than in groups C and K. All animals in group C (100%) and all animals but one in group K (93%) were paraplegic 72 h after the ischemic insult versus 53% in group R and 67% in group RK (P < 0.01 each). More viable motoneurons were present in groups R and RK than in controls (P < 0.05).     

Changes in Properties of Spinal Dorsal Horn Neurons and Their Sensitivity to Morphine after Spinal Cord Injury in the Rat

Background: To gain a better understanding of spinal cord injury (SCI)-induced central neuropathic pain, the authors investigated changes in properties of spinal dorsal horn neurons located rostrally and caudally to the lesion and their sensitivity to morphine in rats after SCI.

Methods: The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to mechanical stimuli of wide-dynamic-range (WDR) and high-threshold neurons rostral and caudal to the lesion were recorded. Effects of cumulative doses of systemic (0.1-3 mg/kg) and spinal (0.1-5 [mu]g) administration of morphine on spontaneous activity and evoked responses to the stimuli of the neurons were evaluated.

Results: Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were only observed in neurons rostral to the SCI site. Significant increases in responses to the mechanical stimuli were seen both in WDR and high-threshold neurons located both rostrally and caudally to the lesion. The responses to nonnoxious and noxious stimuli were significantly greater in caudal WDR neurons than in rostral WDR neurons. In contrast, the responses to pinch stimuli were significantly higher in rostral high-threshold neurons than those in caudal high-threshold neurons. Systemically administered morphine had a greater effect on responses to nonnoxious and noxious stimuli of rostral WDR neurons than those of caudal WDR neurons. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to nonnoxious stimuli compared with those in sham-operated control animals.     

实验性大鼠胚胎脊髓移植对损伤脊髓影响的观察

目的 建立了一个胚胎脊髓（ｆｅｔａｌ ｓｐｉｎａｌ ｃｏｒｄ）组织的低温保存方法笔一个损伤移植模式。方法 通过病理学、组织化学和免疫组织化学的研究,选用胎龄１４天的Ｗｉｓｔａｒ大鼠,分离胚胎脊髓,逐步降温,最后置于液氮中保存。１５天后取出,快速复温,并植入损伤大鼠脊椎内。全部动物于伤后８周处死。结果 经过低温保存的移植物能够在异体脊髓内存活并与宿主组织融合,其在损伤移植区的胶质细胞增生少于对照组。     

Reduction in Torsional Stiffness and Strength at the Proximal Tibia as a Function of Time Since Spinal Cord Injury

Spinal cord injury (SCI) is characterized by marked bone loss and a high rate of low‐energy fracture around regions of the knee. Changes in the mechanical integrity of bone after SCI are poorly defined, and a better understanding may inform approaches to prevent fractures. The purpose of this study was to quantify reductions in torsional stiffness and strength at the proximal tibia as a function of time since SCI. Sixty adults with SCI ranging from 0 to 50 years of duration and a reference group of 10 able‐bodied controls received a CT scan of the proximal tibia. Measures of integral bone mineral were calculated for the total proximal tibia, and localized measures of cortical and trabecular bone mineral were calculated for the epiphysis, metaphysis, and diaphysis. Torsional stiffness (K) and strength (T_ult) for the total proximal tibia were quantified using validated subject‐specific finite element models. Total proximal tibia measures of integral bone mineral, K, and T_ult decreased exponentially (r² = 0.52 to 0.70) and reached a new steady state within 2.1 to 2.7 years after SCI. Whereas new steady‐state values for integral bone mineral and K were 52% to 56% (p < 0.001) lower than the reference group, the new steady state for T_ult was 69% (p < 0.001) lower than the reference group. Reductions in total proximal tibia measures occurred through a combination of trabecular and endocortical resorption, leaving a bone comprised primarily of marrow fat rather than hydroxyapatite. These findings illustrate that a short therapeutic window exists early (ie, 2 years) after SCI, during which bone‐specific intervention may attenuate reductions in mechanical integrity and ultimately prevent SCI‐related fragility fracture. © 2015 American Society for Bone and Mineral Research.     

Blockade of Na sup + and K sup + Currents by Local Anesthetics in the Dorsal Horn Neurons of the Spinal Cord

Background: The dorsal horn of the spinal cord is a pivotal point for transmission of neuronal pain. During spinal and epidural anesthesia, the neurons of the dorsal horn are exposed to local anesthetics. Unfortunately, little is known about the action of local anesthetics on the major ionic conductances in dorsal horn neurons. In this article, the authors describe the effects of bupivacaine, lidocaine, and mepivacaine on voltage-gated Na sup + and K sup + currents in the membranes of these neurons.

Methods: The patch-clamp technique was applied to intact dorsal horn neurons from laminae I-III identified in 200-micro meter slices of spinal cord from newborn rats. Under voltage-clamp conditions, the whole-cell Na sup + and K sup + currents activated by depolarization were recorded in the presence of different concentrations of local anesthetics.

Results: Externally applied bupivacaine, lidocaine, and mepivacaine produced tonic block of Na sup + currents with different potencies. Half-maximum inhibiting concentrations (IC50) were 26, 112, and 324 micro Meter, respectively. All local anesthetics investigated also showed a phasic, that is, a use-dependent, block of Na sup + channels. Rapidly inactivating K sup + currents (KA currents) also were sensitive to the blockers with IC50 values for tonic blocks of 109, 163, and 236 micro Meter, respectively. The block of KA currents was not use dependent. In contrast to Na sup + and KA currents, delayed-rectifier K sup + currents were almost insensitive to the local anesthetics applied.     

甲强龙对兔急性脊髓损伤后血、组织髓鞘碱性蛋白表达的影响

目的探讨大剂量甲强龙(methylprednisolone,MP)对兔急性脊髓损伤后(SCI)血清及髓鞘碱性蛋白(myelinbasicprotein,MBP)表达的影响。方法45只家兔分成3组,Ⅰ组为全椎板切除 生理盐水对照组,Ⅱ组为不完全性SCI 大剂量MP冲击治疗组。Ⅲ组为不完全性SCI 生理盐水。用改良Allens法造成Ⅱ、Ⅲ组不完全性SCI模型,通过ELISA、MBP免疫组化染色进行对比观察血及脊髓组织中MBP的变化。同时进行下肢运动功能评分和脊髓诱发电位测定比较神经功能改变情况。结果大剂量MP治疗组的血清中髓鞘碱性蛋白浓度较单纯损伤组明显下降,病理切片上组织的MBP髓鞘染色明显增加,病理损害减轻。结论大剂量甲强龙(MP)对能下调SCI血中的MBP浓度,减少损伤脊髓髓鞘组织中MBP的释放,从而减轻髓鞘组织的退变促进神经功能恢复。     

脊髓撞击并压迫性损伤减压价值的实验研究

目的　观察脊髓损伤后椎管狭窄程度、减压时间与脊髓神经功能恢复之间的关系。方法　选择新西兰兔 76只 ,分 4组。A组 (对照组 ) 8只 ,L1 椎体前路 ,前后方向钻孔开窗 ;B组 (撞击组 ) 8只 ,经椎体骨窗处 ,72 0gcm力脊髓撞击损伤 ;C组、D组于撞击致伤后 ,从骨窗处置入小螺钉分别造成 <30 %和 >5 0 %的椎管狭窄 ,并根据术后 1 2h ,3、 7、 2 8、 4 2d去除小螺钉 (减压 )的时间不同各分为 5个小组。通过病理 ,SEP检测及免疫学观察 (斜板试验及BBB评分 ) ,观察神经功能恢复的差异性。结果　B组、C组及D组中d8组术后 4 2d与A组相比 ,斜板试验及BBB评分P >0 0 5无统计学意义 ,实验兔运动功能均能恢复。结论　上述实验条件下 ,椎管狭窄程度 <30 % ,进行或不进行椎管减压 ,脊髓神经功能均可在 4 2d内恢复 ;椎管狭窄 >5 0 % ,1 2h内减压 ,神经功能基本恢复 ,3d后减压神经功能大部分丧失     

大剂量甲基强的松龙对急性脊髓损伤的疗效及预后判断

目的探讨大剂量甲基强的松龙（methylprednisolone,MP）对急性脊髓损伤（acute spinal cord injury,ASCI）的疗效、并发症防治及预后判断。方法将38例ASCI患者根据影像学改变和脊髓功能丧失程度分轻、中、重三度。轻度10例,影像检查无明显异常、脊髓功能部分丧失;中度21例,影像检查轻至中度异常（椎管轻至中度占位,MRI脊髓有信号改变）、脊髓功能部分丧失;重度7例,影像检查重度异常（椎管中至重度占位,MRI显示脊髓断裂）、脊髓功能完全丧失。38例患者在受伤8 h内按NASCIS方案接受MP冲击治疗,分析其疗效和判断预后。结果经6周及6个月随访,MP对轻、中度组患者疗效显著,预后好;重度组疗效及预后差。38例患者住院治疗及随访过程中除1例发生上消化道出血,余无伤口感染、延迟愈合、肺部感染、心率失常等并发症。结论大剂量MP冲击治疗对急性脊髓损伤患者安全有效,对轻、中度患者疗效显著,预后好。