Systemic Administration of Rolipram Increases Medullary and Spinal cAMP and Activates a Latent Respiratory Motor Pathway After High Cervical Spinal Cord Injury

Background/Objective: High cervical spinal cord hemisection interrupts descending respiratory drive from the rostral ventral respiratory group in the medulla to the ipsilateral phrenic motoneurons. Hemisection results in the paralysis of the ipsilateral hemidiaphragm. Chronic administration of rolipram, a specific phosphodiesterase-IV inhibitor, promotes synaptic plasticity and restores phrenic nerve function after a high cervical spinal cord lesion. Here, we test the hypothesis that an acute administration of rolipram will increase spinal and medullary levels of 3′,5′-cyclic adenosine monophosphate (cAMP) and induce phrenic nerve recovery after cervical (C2) spinal cord hemisection.

Methods: Male Sprague-Dawley rats were subjected to left C2 hemisection surgery 1 week before experimentation. Bilateral phrenic nerve activity was recorded in anesthetized, vagotomized, and pancuronium paralyzed rats, and rolipram was intravenously applied (2 mg/kg).

Results: Intravenous administration of rolipram increased phrenic nerve output in uninjured control and left C2 spinal cord-hemisected rats. In addition, rolipram restored respiratory-related activity to the left phrenic nerve made quiescent by the hemisection. In both uninjured and hemisected rats, rolipram significantly enhanced phrenic inspiratory burst amplitude and burst area compared with predrug values. Also, rolipram concomitantly increased spinal and medullary cAMP.

Conclusions: These results suggest that a phosphodiesterase inhibitor capable of elevating cAMP levels can enhance phrenic nerve output and restore respiratory-related phrenic nerve function after high cervical spinal cord injury. Thus, targeting the cAMP signaling cascade can be a useful therapeutic approach in promoting synaptic efficacy and respiratory recovery after cervical spinal cord injury.     

无骨折脱位型颈髓损伤的手术治疗分析

目的总结分析无骨折脱位型颈髓损伤患者的手术疗效。方法自2010年1月至2013年12月,对30例采用手术治疗的无骨折脱位型颈髓损伤患者的临床资料进行回顾性分析,并比较手术前后JOA评分。结果术前JOA评分5.1±1.6,术后随访时为11.8±1.7,差异有显著统计学意义(P0.01),JOA改善率为56.3%。结论手术治疗无骨折脱位型颈髓损伤的基本原则是早期减压与稳定,根据患者的影像学特点,有针对性地选择手术方式,可获得较满意的疗效。     

Hemodynamic Parameters and Timing of Surgical Decompression in Acute Cervical Spinal Cord Injury

Abstract

Background/Objectives: To evaluate the relationship between the severity of cervical spinal cord injury (SCI) (American Spinal Injury Association [ASIA] grade), presence of neurogenic shock, and timing of surgical intervention. This is a post-hoc analysis from the Sygen multicenter randomized controlled trial.

Methods: Blood pressure (BP) and heart rate (HR) data were collected when patients were first assessed in the emergency room (Time A) and at the time of randomization (Time B). Individuals were subdivided by ASIA grade and by the level of the systolic BP (SBP).

Results: Only individuals with cervical SCI from the Sygen trial (n = 577) were evaluated. Severe complete SCI (ASIA grade = A) was established in 57% of these patients. A total of 74 (13%) patients with neurogenic shock (SBP < 90 mmHg) at Time A were identified. The SBP increased significantly from Time A to Time B (P < 0.0001). The median time from SCI to surgical intervention, for ASIA A, was 80.9 hours for patients with initial SBP < 90 mmHg and 58 hours for patients with initial SBP > 90 mmHg (P = 0.025). Multivariable analysis after adjusting for confounders revealed a statistically significant difference in the time to surgical intervention based on SBP for ASIA A (P = 0.026), yet not for ASIA B or C/D.

Conclusions: The presence of neurogenic shock was associated with a delay in the timing of surgical intervention in patients with cervical SCI. Detailed evaluation of autonomic dysfunctions following SCI including cardiovascular instability could improve our understanding of the complexities of clinical presentations and possible neurological outcomes.     

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.