Gabapentinoids Are Effective in Decreasing Neuropathic Pain and Other Secondary Outcomes After Spinal Cord Injury: A Meta-Analysis

Objective

To examine the effectiveness of gabapentin and pregabalin in diminishing neuropathic pain and other secondary conditions in individuals with spinal cord injury (SCI).

Data Sources

A systematic search was conducted using multiple databases for relevant articles published from 1980 to June 2013.

Study Selection

Controlled and uncontrolled trials involving gabapentin and pregabalin for treatment of neuropathic pain, with ≥3 subjects and ≥50% of study population with SCI, were included.

Data Extraction

Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen's d to calculate standardized mean difference (SMD), SE, and 95% confidence interval (CI) for primary (pain) and secondary outcomes (anxiety, depression, sleep interference) was conducted.

Data Synthesis

Eight studies met inclusion criteria. There was a significant reduction in the intensity of neuropathic pain at <3 months (SMD=.96±.11; 95% CI, .74–1.19; P<.001) and between 3 and 6 months (SMD=2.80±.18; 95% CI, 2.44–3.16; P<.001). A subanalysis found a significant decrease in pain with gabapentin (SMD=1.20±.16; 95% CI, .88–1.52; P<.001) and with pregabalin (SMD=1.71±.13; 95% CI, 1.458–1.965; P<.001). A significant reduction in other SCI secondary conditions, including sleep interference (SMD=1.46±.12; 95% CI, 1.22–1.71; P<.001), anxiety (SMD=1.05±.12; 95% CI, .81–1.29; P<.001), and depression (SMD=1.22±.13; 95% CI, .967–1.481; P<.001) symptoms, was shown. A significantly higher risk of dizziness (risk ratio [RR]=2.02, P=.02), edema (RR=6.140, P=.04), and somnolence (RR=1.75, P=.01) was observed.

Conclusions

Gabapentin and pregabalin appear useful for treating pain and other secondary conditions after SCI. Effectiveness comparative to other analgesics has not been studied. Patients need to be monitored closely for side effects.     

A Systematic Review of the Management of Autonomic Dysreflexia After Spinal Cord Injury

Krassioukov A, Warburton DE, Teasell R, Eng JJ, Spinal Cord Injury Rehabilitation Evidence Research Team. A systematic review of the management of autonomic dysreflexia after spinal cord injury.

Objective

To review systematically the clinical evidence on strategies to prevent and manage autonomic dysreflexia (AD).

Data Sources

A key word search of several databases (Medline, CINAHL, EMBASE, and PsycINFO), in addition to manual searches of retrieved articles, was undertaken to identify all English-language literature evaluating the efficacy of interventions for AD.

Study Selection

Studies selected for review included randomized controlled trials (RCTs), prospective cohort studies, and cross-sectional studies. Treatments reviewed included pharmacologic and nonpharmacologic interventions for the management of AD in subjects with spinal cord injury. Studies that failed to assess AD outcomes (eg, blood pressure) or symptoms (eg, headaches, sweating) were excluded.

Data Extraction

Studies were critically reviewed and assessed for their methodologic quality by 2 independent reviewers.

Data Synthesis

Thirty-one studies were assessed, including 6 RCTs. Preventative strategies to reduce the episodes of AD caused by common triggers (eg, urogenital system, surgery) primarily were supported by level 4 (pre-post studies) and level 5 (observational studies) evidence. The initial acute nonpharmacologic management of an episode of AD (ie, positioning the patient upright, loosening tight clothing, eliminating any precipitating stimulus) is supported by clinical consensus and physiologic data (level 5 evidence). The use of antihypertensive drugs in the presence of sustained elevated blood pressure is supported by level 1 (prazosin) and level 2 evidence (nifedipine and prostaglandin E₂).

Conclusions

A variety of options are available to prevent AD (eg, surgical, pharmacologic) and manage the acute episode (elimination of triggers, pharmacologic); however, these options are predominantly supported by evidence from noncontrolled trials, and more rigorous trials are required.     

Employment Trajectories After Spinal Cord Injury: Results From a 5-Year Prospective Cohort Study

Objectives

To identify different employment trajectories in individuals with spinal cord injury (SCI) after discharge from initial rehabilitation and to determine predictors of different trajectories from demographic, injury, functional, and psychological characteristics.

Design

Prospective cohort study with baseline measurement at the start of active rehabilitation, a measurement at discharge, and follow-up measurements at 1, 2, and 5 years after discharge.

Setting

Eight rehabilitation centers with SCI units in The Netherlands.

Participants

People with acute SCI (N=176), aged between 18 and 60 years at baseline, who completed at least 2 follow-up measurements.

Interventions

Not applicable.

Main Outcome Measure

Employment was defined as having paid work for ≥12h/wk.

Results

Using latent class growth mixture modeling, 3 distinct employment trajectories were identified: (1) no employment group (22.2%), that is, participants without employment pre-SCI and during 5-year follow-up; (2) low employment group (56.3%), that is, participants with pre-SCI employment and a low, slightly increasing probability of employment during 5-year follow-up; and (3) steady employment group (21.6%), that is, participants with continuous employment pre-SCI and within 5-year follow-up. Predictors of steady employment versus low employment were having secondary education (odds ratio, 4.32; 95% confidence interval, 1.69–11.02) and a higher FIM motor score (odds ratio, 1.04; 95% confidence interval, 1.01–1.06) at discharge.

Conclusions

Distinct employment trajectories after SCI were identified. More than half of the individuals with SCI had a low employment trajectory, and only one-fifth of the individuals with SCI had a steady employment trajectory. Secondary education and higher functional independence level predicted steady employment.     

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

Teasell RW, Mehta S, Aubut JL, Foulon B, Wolfe DL, Hsieh JTC, Townson AF, Short C, the Spinal Cord Injury Rehabilitation Evidence Research Team. A systematic review of pharmacologic treatments of pain after spinal cord injury.

Objective

To conduct a systematic review of published research on the pharmacologic treatment of pain after spinal cord injury (SCI).

Data Sources

MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles published 1980 to June 2009 addressing the treatment of pain post SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database (PEDro) assessment scale, whereas non-RCTs were assessed by using the Downs and Black (D&B) evaluation tool. A level of evidence was assigned to each intervention by using a modified Sackett scale.

Study Selection

The review included RCTs and non-RCTs, which included prospective controlled trials, cohort, case series, case-control, pre-post studies, and post studies. Case studies were included only when there were no other studies found.

Data Extraction

Data extracted included the PEDro or D&B score, the type of study, a brief summary of intervention outcomes, the type of pain, the type of pain scale, and the study findings.

Data Synthesis

Articles selected for this particular review evaluated different interventions in the pharmacologic management of pain after SCI. Twenty-eight studies met inclusion criteria; there were 21 randomized controlled trials; of these, 19 had level 1 evidence. Treatments were divided into 5 categories: anticonvulsants, antidepressants, analgesics, cannabinoids, and antispasticity medications.

Conclusions

Most studies did not specify participants' types of pain, making it difficult to identify the type of pain being targeted by the treatment. Anticonvulsant and analgesic drugs had the highest levels of evidence and were the drugs most often studied. Gabapentin and pregabalin had strong evidence (5 level 1 RCTs) for effectiveness in treating post-SCI neuropathic pain as did intravenous analgesics (lidocaine, ketamine, and morphine), but the latter only had short-term benefits. Tricyclic antidepressants only showed benefit for neuropathic pain in depressed persons. Intrathecal baclofen reduced musculoskeletal pain associated with spasticity; however, there was conflicting evidence for the reduction in neuropathic pain. Studies assessing the effectiveness of opioids were limited and revealed only small benefits. Cannabinoids showed conflicting evidence in improving spasticity-related pain. Clonidine and morphine when given together had a significant synergistic neuropathic pain-relieving effect.     

Effects of Locomotor Training After Incomplete Spinal Cord Injury: A Systematic Review

Objective

To provide an overview of, and evaluate the current evidence on, locomotor training approaches for gait rehabilitation in individuals with incomplete spinal cord injury to identify the most effective therapies.

Data Sources

The following electronic databases were searched systematically from first date of publication until May 2013: Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, MEDLINE, Physiotherapy Evidence Database, and PubMed. References of relevant clinical trials and systematic reviews were also hand searched.

Study Selection

Only randomized controlled trials evaluating locomotor therapies after incomplete spinal cord injury in an adult population were included. Full-text versions of all relevant articles were selected and evaluated by both authors.

Data Extraction

Eligible studies were identified, and methodologic quality was assessed with the Physiotherapy Evidence Database scale. Articles scoring <4 points on the scale were excluded. Sample population, interventions, outcome measures, and findings were evaluated with regard to walking capacity, velocity, duration, and quality of gait.

Data Synthesis

Data were analyzed by systematic comparison of findings. Eight articles were included in this review. Five compared body-weight–supported treadmill training (BWSTT) or robotic-assisted BWSTT with conventional gait training in acute/subacute subjects (≤1y postinjury). The remaining studies each compared 3 or 4 different locomotor interventions in chronic participants (>1y postinjury). Sample sizes were small, and study designs differed considerably impeding comparison. Only minor differences in outcomes measures were found between groups. Gait parameters improved slightly more after BWSTT and robotic gait training for acute participants. For chronic participants, improvements were greater after BWSTT with functional electrical stimulation and overground training with functional electrical stimulation/body-weight support compared with BWSTT with manual assistance, robotic gait training, or conventional physiotherapy.

Conclusions

Evidence on the effectiveness of locomotor therapy is limited. All approaches show some potential for improvement of ambulatory function without superiority of 1 approach over another. More research on this topic is required.     

Venous Thromboembolism After Spinal Cord Injury

Teasell RW, Hsieh JT, Aubut JL, Eng JJ, Krassioukov A, Tu L, for the Spinal Cord Injury Rehabilitation Evidence Review Research Team. Venous thromboembolism after spinal cord injury.

Objective

To review systematically the published literature on the treatment of deep venous thromboembolism after spinal cord injury (SCI).

Data Sources

MEDLINE/PubMed, CINAHL, EMBASE, and PsycINFO databases were searched for articles addressing the treatment of deep venous thromboembolism post-SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database Scale, while non-RCTs were assessed using the Downs and Black evaluation tool.

Study Selection

Studies included RCTs, non-RCTS, cohort, case-control, case series, pre-post, and postinterventional studies. Case studies were included only when no other studies were available.

Data Extraction

Data extracted included demographics, the nature of the study intervention, and study results.

Data Synthesis

Levels of evidence were assigned to the interventions using a modified Sackett scale.

Conclusions

Twenty-three studies met inclusion criteria. Thirteen studies examined various pharmacologic interventions for the treatment or prevention of deep venous thrombosis in patients with SCI. There was strong evidence to support the use of low-molecular-weight heparin in reducing venous thrombosis events, and a higher adjusted dose of unfractionated heparin was found to be more effective than 5000 units administered every 12 hours, although bleeding complications were more common. Nonpharmacologic treatments were also reviewed, but again limited evidence was found to support these treatments.     

A Systematic Review of the Management of Orthostatic Hypotension After Spinal Cord Injury

Krassioukov A, Eng JJ, Warburton DE, Teasell R, Spinal Cord Injury Rehabilitation Evidence Research Team. A systematic review of the management of orthostatic hypotension after spinal cord injury.

Objective

To review systematically the evidence for the management of orthostatic hypotension (OH) in patients with spinal cord injuries (SCIs).

Data Sources

A key word literature search was conducted of original and review articles as well as practice guidelines using Medline, CINAHL, EMBASE, and PsycInfo, and manual searches of retrieved articles from 1950 to July 2008, to identify literature evaluating the effectiveness of currently used treatments for OH.

Study Selection

Included randomized controlled trials (RCTs), prospective cohort studies, case-control studies, pre-post studies, and case reports that assessed pharmacologic and nonpharmacologic intervention for the management of OH in patients with SCI.

Data Extraction

Two independent reviewers evaluated the quality of each study, using the Physiotherapy Evidence Database score for RCTs and the Downs and Black scale for all other studies. Study results were tabulated and levels of evidence assigned.

Data Synthesis

A total of 8 pharmacologic and 21 nonpharmacologic studies were identified that met the criteria. Of these 26 studies (some include both pharmacologic and nonpharmacologic interventions), only 1 pharmacologic RCT was identified (low-quality RCT producing level 2 evidence), in which midodrine was found to be effective in the management of OH after SCI. Functional electrical stimulation was one of the only nonpharmacologic interventions with some evidence (level 2) to support its utility.

Conclusions

Although a wide array of physical and pharmacologic measures are recommended for the management of OH in the general population, very few have been evaluated for use in SCI. Further research needs to quantify the efficacy of treatment for OH in subjects with SCI, especially of the many other pharmacologic interventions that have been shown to be effective in non-SCI conditions.     

硬膜外脓肿的MRI分析

目的 探讨MRI对硬膜外脓肿的诊断价值。方法 对经MRI检查并经穿刺或手术病理证实的11例硬膜外脓肿进行回顾性分析。结果 11例中发生于颅内5例，椎管内6例，其MRI表现；断面上显示为在颅板下或椎管内的梭形或长圆形异常信号影，T1WI上表现为均匀或不均匀的低，略低或等信号影，周边为略低或等信号的较厚边缘，少部分（2例）有分隔；T2WI上多表现为较明显的高信号，少数呈等，略高信号，并可见略低或等信号的边缘（或分隔）；增强扫描病灶边缘（及分隔）明显强化，其内无明显强化或不强化，1例病灶呈较均匀的强化，1例病灶部分呈片状强化，脓肿周围表现，脑实质或脊髓均见受压移位，部分颅骨或脊柱骨质信号有改变。结论 MRI能清晰显示硬膜外脓肿的大小，形状，范围，内部结构及与周围结构关系。