Use of an arginine-enriched oral nutrition supplement in the healing of pressure ulcers in patients with spinal cord injuries : an observational study

Aim: Pressure ulcers are a serious secondary consequence of spinal cord injuries. The objective of the present study was to determine whether an arginine-containing nutritional supplement can reduce the healing time of pressure ulcers in people with spinal cord injuries compared with those not consuming the supplement until full wound healing.

Methods: Thirty-four spinal cord injured patients with a grade 2, 3 or 4 pressure ulcer were prescribed two 237 mL tetrapaks/day of a supplement containing additional protein, arginine, zinc and vitamin C. Pressure ulcer healing was assessed with the Pressure Ulcer Scale for Healing tool.

Results: Twenty patients consumed the nutritional supplement until full pressure ulcer healing had occurred, while 14 patients ceased consuming the supplement before full healing occurred because of intolerance, compliance or taste issues. A 2.5-fold greater rate of healing was observed in patients consuming the supplement until full healing compared with those who ceased taking the supplement (8.5 ± 1.1 weeks vs 20.9 ± 7.0 weeks respectively; P = 0.04). There were no significant differences in age, nutritional status, gender or reason for admission between groups. Comparison of healing rates in the group consuming the supplement to full wound healing against expected rates derived from the medical literature showed a significantly shorter time-to-healing (grade 3 pressure ulcer: 6.5 ± 0.8 weeks vs 18.2 weeks; grade 4: 11.4 ± 2.0 weeks vs 22.1 weeks; P < 0.001).

Conclusion: The present small-scale study demonstrated the potential for specialised wound healing nutritional supplements to shorten the time to pressure ulcer healing in spinal cord injured patients.

Burden of care and its impact on health-related quality of life of caregivers of individuals with spinal cord injury

Objective: to analyze the impact and burden of care on the Health-Related Quality of Life (HRQOL) of caregivers of individuals with a spinal cord injury (SCI). Method: cross-sectional observational study carried out by reviewing medical records and applying questionnaires. The scale Short Form 36 (SF-36) was used to assess HRQOL and the Caregiver Burden Scale (CBScale) for care burden. Results were analyzed quantitatively. Most patients with SCIs were male, aged 35.4 years old on average, with a predominance of thoracic injuries followed by cervical injuries. Most caregivers were female aged 44.8 years old on average. Results: tetraplegia and secondary complications stand out among the clinical characteristics that contributed to greater care burden and worse HRQOL. Association between care burden with HRQOL revealed that the greater the burden the worse the HRQOL. Conclusion: Preventing care burden through strategies that prepare patients for hospital discharge, integrating the support network, and enabling access to health care services are interventions that could minimize the effects arising from care burden and contribute to improving HRQOL.

Effect of Acute Administration of Angiopoietin-1 in Experimental Traumatic Spinal Cord Injury: Magnetic Resonance Imaging and Neurobehavioral Studies

Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI. In these studies, angiopoietin-1 (Ang1), an agent known to reduce vascular permeability, was hypothesized to attenuate the severity of secondary injuries of SCI. Using longitudinal magnetic resonance imaging (MRI) studies (dynamic contrast-enhanced [DCE]-MRI for quantification of BSCB permeability, highresolution anatomical MRI for calculation of lesion size, and diffusion tensor imaging for assessment of axonal integrity), the acute, subacute, and chronic effects of Ang1 administration after SCI were evaluated. Neurobehavioral assessments were also performed. These non-invasive techniques have applicability to the monitoring of therapies in patients with SCI. In the acute phase of injury, Ang1 was found to reduce BSCB permeability and improve neuromotor recovery. Dynamic contrast-enhanced MRI revealed a persistent compromise of the BSCB up to two months post-injury. In the subacute phase of injury, Ang1’s effect on reducing BSCB permeability was maintained and it was found to transiently reduce axonal integrity. The SCI lesion burden was assessed with an objective method that compared favorably with segmentations from human raters. In the chronic phase of injury, Ang1 resulted in maintained reduction in BSCB permeability, a decrease in lesion size, and improved axonal integrity. Finally, longitudinal correlations among data from the MRI modalities and neurobehavioral assays were evaluated. Locomotor recovery was negatively correlated with lesion size in the Ang1 cohort and positively correlated with diffusion measures in the vehicle cohort. In summary, the results demonstrate a possible role for Ang1 in mitigating the secondary pathologies of SCI during the acute and chronic phases of injury.

Owner-perceived, weighted quality-of-life assessments in dogs with spinal cord injuries.

OBJECTIVE To evaluate changes over time in owner-perceived, weighted quality-of-life assessments in dogs with spinal cord injuries and determine whether scores were associated with underlying etiology or with veterinarian-assigned scores for severity of neurologic dysfunction. DESIGN Cohort study. ANIMALS 100 dogs with spinal cord injury. PROCEDURES Duration of dysfunction, modified Frankel neurologic injury score, and etiology were recorded. At initial and recheck (4- to 6-week) evaluations, owners were asked to identify 5 areas or activities they believed had the most influence on their dogs' quality of life, assess their dogs' current status in each area, and provide a weighting for the importance of each area; results were used to construct a weighted quality-of-life score. Owners were also asked to provide a quality-of-life score with a visual analog scale (VAS). RESULTS At initial and recheck evaluations, weighted quality-of-life scores were higher for ambulatory than for nonambulatory dogs. However, scores did not differ among groups when dogs were grouped on the basis of underlying etiology or duration of injury. Dogs with an increase in Frankel score between the initial and recheck evaluations had a significant increase in weighted quality-of-life score, whereas for dogs that did not have any change in Frankel score, initial and recheck weighted quality-of-life scores were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that owner-assigned, weighted quality-of-life scores for dogs with spinal cord injuries did not vary significantly on the basis of underlying etiology or duration of injury but were higher for ambulatory than for nonambulatory dogs.

Evaluation of a questionnaire for obtaining owner-perceived, weighted quality-of-life assessments for dogs with spinal cord injuries.

OBJECTIVE To evaluate a questionnaire for obtaining owner-perceived, weighted quality-oflife assessments for dogs with spinal cord injuries. DESIGN Evaluation study. Animals-100 dogs with spinal cord injuries and 48 healthy control dogs. PROCEDURES The questionnaire was adapted from a questionnaire (the schedule for the evaluation of individual quality of life-direct weighting) used for human patients. Specifically, owners were asked to identify 5 areas or activities they believed had the most influence on their dogs' quality of life, assess their dogs' current status in each of those areas, and provide a weighting for the importance of each area. Results were used to construct a weighted quality-of-life score ranging from 0 to 100 for each dog. Owners were also asked to provide a quality-of-life score with a visual analog scale (VAS). RESULTS A good correlation was found between weighted and VAS quality-of-life scores. Dogs with spinal cord injuries had weighted quality-of-life scores that were significantly lower than scores for control dogs. Quality-of-life areas and activities provided by owners of dogs with spinal cord injuries were similar to areas and activities provided by owners of healthy control dogs and could mostly be encompassed by 5 broader domains: mobility, play or mental stimulation, health, companionship, and other. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the questionnaire could be used to obtain owner-perceived, weighted quality-of-life assessments for dogs with spinal cord injuries. Obtaining owner-perceived quality-of-life assessments for individual dogs should allow veterinarians to better address quality-of-life concerns and expectations of owners.

Bone morphology of the femur and tibia captured by statistical shape modelling predicts rapid bone loss in acute spinal cord injury patients

We would like to thank the study participants and the clinical and research staff at the Queen Elizabeth National Spinal Injury Unit, as without them this study would not have been possible. We are grateful for the funding received from Glasgow Research Partnership in Engineering for the employment of SC during data collection for this study. We would like to thank the Royal Society of Edinburgh's Scottish Crucible scheme for providing the opportunity for this collaboration to occur. We are also indebted to Maria Dumitrascuta for her time and effort in producing inter-repeatability results for the shape models.

Bone morphology of the femur and tibia captured by statistical shape modelling predicts rapid bone loss in acute spinal cord injury patients

We would like to thank the study participants and the clinical and research staff at the Queen Elizabeth National Spinal Injury Unit, as without them this study would not have been possible. We are grateful for the funding received from Glasgow Research Partnership in Engineering for the employment of SC during data collection for this study. We would like to thank the Royal Society of Edinburgh's Scottish Crucible scheme for providing the opportunity for this collaboration to occur. We are also indebted to Maria Dumitrascuta for her time and effort in producing inter-repeatability results for the shape models.

Short form health surveys and related variants in spinal cord injury research : a systematic review

CONTEXT: 'Short Form' health surveys - such as the SF-36 and SF-12 - are widely used in medical research. Spinal cord injury (SCI) is no exception, despite oft-cited concerns regarding measurement properties for populations with physical impairment.OBJECTIVE: To provide a comprehensive overview of the use of Short Form health surveys and their variants within the SCI literature.METHODS: Papers published between database inception and September 2012 were identified from 11 electronic databases; a supplementary reference list search was also conducted. Data extraction focused on details regarding the range of different Short Form surveys and variants used in SCI research, the respective frequency of use, the nature of reporting (complete versus partial reporting) and the method of survey administration.RESULTS: One hundred seventy-four papers were identified. Thirty-six-item Short Form health surveys were frequently administered as complete instruments (n = 82); in 69 of these 82 studies (84%), it was not clearly stated which 36-item version had been used (e.g. SF-36v1, SF-36v2, RAND-36). Data for individual items and domains were often reported (29% of identified studies), indicating significant partial use of standardized measures. Modified variants of standardized health surveys were administered in 12 studies.CONCLUSION: Although standardized Short Form health surveys are common within SCI research, attempts to add, delete, or modify items have resulted in a number of variants, often with minimal supportive psychometric evidence. Using established, generic outcome measures is appealing for a number of reasons. However, validity is paramount and requires further explicit consideration within the SCI research community.

Design and rationale of a Prospective, Observational European Multicenter study on the efficacy of acute surgical decompression after traumatic Spinal Cord Injury: the SCI-POEM study

Objectives:Despite many years of research, there is currently no treatment available that results in major neurological or functional recovery after traumatic spinal cord injury (tSCI). In particular, no conclusive data related to the role of the timing of decompressive surgery, and the impact of injury severity on its benefit, have been published to date. This paper presents a protocol that was designed to examine the hypothesized association between the timing of surgical decompression and the extent of neurological recovery in tSCI patients.Study design: The SCI-POEM study is a Prospective, Observational European Multicenter comparative cohort study. This study compares acute (<12 h) versus non-acute (>12 h, <2 weeks) decompressive surgery in patients with a traumatic spinal column injury and concomitant spinal cord injury. The sample size calculation was based on a representative European patient cohort of 492 tSCI patients. During a 4-year period, 300 patients will need to be enrolled from 10 trauma centers across Europe. The primary endpoint is lower-extremity motor score as assessed according to the 'International standards for neurological classification of SCI' at 12 months after injury. Secondary endpoints include motor, sensory, imaging and functional outcomes at 3, 6 and 12 months after injury.Conclusion:In order to minimize bias and reduce the impact of confounders, special attention is paid to key methodological principles in this study protocol. A significant difference in safety and/or efficacy endpoints will provide meaningful information to clinicians, as this would confirm the hypothesis that rapid referral to and treatment in specialized centers result in important improvements in tSCI patients.Spinal Cord advance online publication, 17 April 2012; doi:10.1038/sc.2012.34.

An acute growth factor treatment that preserves function after spinal cord contusion injury

Inflammation of the spinal cord after traumatic spinal cord injury leads to destruction of healthy tissue. This “secondary degeneration” is more damaging than the initial physical damage and is the major contributor to permanent loss of functions. In our previous study we showed that combined delivery of two growth factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), significantly reduced secondary degeneration after hemi-section injury of the spinal cord in the rat. Growth factor treatment reduced the size of the lesion cavity at 30d compared to control animals and further reduced the cavity at 90d in treated animals while in control animals the lesion cavity continued to increase in size. Growth factor treatment also reduced astrogliosis and reduced macroglia/macrophage activation around the injury site. Treatment with individual growth factors alone had similar effects to control treatments. The present study investigated whether growth factor treatment would improve locomotor behaviour after spinal contusion injury, a more relevant preclinical model of spinal cord injury. The growth factors were delivered for the first 7d to the injury site via osmotic minipump. Locomotor behaviour was monitored at 1-28d after injury using the BBB score and at 30d using automated gait analysis. Treated animals had BBB scores of 18; Control animals scored 10. Treated animals had significantly reduced lesion cavities and reduced macroglia/macrophage activation around the injury site. We conclude that growth factor treatment preserved spinal cord tissues after contusion injury, thereby allowing functional recovery. This treatment has the potential to significantly reduce the severity of human spinal cord injuries.

Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance.

Release of endogenous dynorphin opioids within the spinal cord after partial sciatic nerve ligation (pSNL) is known to contribute to the neuropathic pain processes. Using a phosphoselective antibody [kappa opioid receptor (KOR-P)] able to detect the serine 369 phosphorylated form of the KOR, we determined possible sites of dynorphin action within the spinal cord after pSNL. KOR-P immunoreactivity (IR) was markedly increased in the L4-L5 spinal dorsal horn of wild-type C57BL/6 mice (7-21 d) after lesion, but not in mice pretreated with the KOR antagonist nor-binaltorphimine (norBNI). In addition, knock-out mice lacking prodynorphin, KOR, or G-protein receptor kinase 3 (GRK3) did not show significant increases in KOR-P IR after pSNL. KOR-P IR was colocalized in both GABAergic neurons and GFAP-positive astrocytes in both ipsilateral and contralateral spinal dorsal horn. Consistent with sustained opioid release, KOR knock-out mice developed significantly increased tactile allodynia and thermal hyperalgesia in both the early (first week) and late (third week) interval after lesion. Similarly, mice pretreated with norBNI showed enhanced hyperalgesia and allodynia during the 3 weeks after pSNL. Because sustained activation of opioid receptors might induce tolerance, we measured the antinociceptive effect of the kappa agonist U50,488 using radiant heat applied to the ipsilateral hindpaw, and we found that agonist potency was significantly decreased 7 d after pSNL. In contrast, neither prodynorphin nor GRK3 knock-out mice showed U50,488 tolerance after pSNL. These findings suggest that pSNL induced a sustained release of endogenous prodynorphin-derived opioid peptides that activated an anti-nociceptive KOR system in mouse spinal cord. Thus, endogenous dynorphin had both pronociceptive and antinociceptive actions after nerve injury and induced GRK3-mediated opioid tolerance.

Necrospermia and chronic spinal cord injury.

OBJECTIVE: To determine whether improvement in quality of semen over 4 consecutive days of electroejaculation in men with chronic spinal cord injury (SCI) was consistent with epididymal necrospermia. DESIGN: Prospective study of a random sample of men with SCI. SETTING: A southeastern Australian SCI management center in collaboration with the specialist andrology service of a university-based department of obstetrics and gynecology in a tertiary referral hospital. PATIENT(S): Nine men with chronic spinal cord injury. INTERVENTION(S): Semen samples were obtained by using electroejaculation, and testicular biopsy samples were obtained by using fine-needle tissue aspiration. MAIN OUTCOME MEASURE(S): Semen analysis was performed according to World Health Organization criteria. Testicular biopsy and electron microscopy were done by using standard techniques. RESULT(S): During up to 4 days of consecutive-day electroejaculation, sperm motility and viability in semen obtained from men with chronic SCI increased by an average of 23% on days 2 and 3. The severity of the degenerative changes and the numbers of spermatozoa affected on day 1 became less marked by day 4. The changes were not present in late spermatids obtained from testicular biopsies. CONCLUSION(S): The asthenospermia of chronic SCI is similar to epididymal necrospermia and can be improved by consecutive-day electroejaculation.

Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury

Introduction Changes in the distribution of interstitial cells (IC) are reportedly associated with dysfunctional bladder. The present study investigated whether spinal cord injury (SCI) resulted in changes to IC subpopulations (vimentin-positive with the ultrastructural profile of IC), smooth muscle and nerves within the bladder wall and correlated cellular remodelling with functional properties. Methods Bladders from SCI (T8/9 transection) and sham-operated rats five-weeks post-injury were used for ex vivo pressure-volume experiments or processed for morphological analysis with transmission electron microscopy (TEM) and light/confocal microscopy. Results Pressure-volume relationships revealed low-pressure, hypercompliance in SCI bladders indicative of decompensation. Extensive networks of vimentin-positive IC were typical in sham lamina propria and detrusor but were markedly reduced post-SCI; semi-quantitative analysis showed significant reduction. Nerves labelled with anti-neurofilament and anti-vAChT were notably decreased post-SCI. TEM revealed lamina propria IC and detrusor IC which formed close synaptic-like contacts with vesicle-containing nerve varicosities in shams. Lamina propria and detrusor IC were ultrastructurally damaged post-SCI with retracted/lost cell processes and were adjacent to areas of cellular debris and neuronal degradation. Smooth muscle hypertrophy was common to SCI tissues. Conclusions IC populations in bladder wall were decreased five weeks post-SCI, accompanied with reduced innervation, smooth muscle hypertrophy and increased compliance. These novel findings indicate that bladder wall remodelling post-SCI affects the integrity of interactions between smooth muscle, nerves and IC, with compromised IC populations. Correlation between IC reduction and a hypercompliant phenotype suggests that disruption to bladder IC contribute to pathophysiological processes underpinning the dysfunctional SCI bladder.

Use of adhesion counts to help predict symptomatic infection and the ability of fluoroquinolones to penetrate bacterial biofilms on the bladder cells of spinal cord injured patients

There were three objectives to the present study: (1) compare the bladder infection rate and extent of biofilm formation for seven untreated spinal cord injured (SCI) patients and seven given prophylactic co-trimoxazole, (2) identify a level of bacterial adhesion to bladder cells which could be used to help predict symptomatic infection, and (3) determine from in vivo and in vitro studies whether fluoroquinolones were effective at penetrating bacterial biofilms. The results showed that the infection rate had not changed with the introduction of prophylaxis. However, the uropathogenic population had altered subsequent to the introduction of prophylaxis with E. coli being replaced by E. faecalis as the most common cause of infection. In 63% of the specimens from asymptomatic patients, the bacterial counts per cell were <20, while 81% of specimens from patients with at least one sign and one symptom of urinary tract infection (UTI) had > 20 adherent bacteria per bladder cell. Therefore, it is proposed that counts of > 20 bacteria adherent to sediment transitional epithelial bladder cells may be predictive of symptomatic UTI. Clinical data showed that fluoroquinolone therapy reduced the adhesion counts to <20 per cell in 63% of cases, while trimethoprim-sulfamethoxazole only did so in 44%. Further in vitro testing showed that ciprofloxacin (0.1, 0.5 and 1.0 micrograms/ml) partially or completely eradicated adherent biofilms from 92% of spinal cord injured patients' bladder cells, while ofloxacin did so in 71% cases and norfloxacin in 56%. These findings have important implications for the detection and treatment of bacteriuria in spinal cord injured patients.