Chronic Spinal Cord Injury Patients Research Articles

Safety profile, feasibility and early clinical outcome of cotransplantation of olfactory mucosa and bone marrow stem cells in chronic spinal cord injury patients.

Study DesignProspective case series.PurposeTo study the safety and feasibility of cotransplantation of bone marrow stem cells and autologous olfactory mucosa in chronic spinal cord injury.Overview of LiteratureStem cell therapies are a novel method in the attempt to restitute heavily damaged tissues. We discuss our experience with this modality in postspinal cord injury paraplegics.MethodsThe study includes 9 dorsal spine injury patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A neurological impairment who underwent de-tethering of the spinal cord followed by cotransplantation with bone marrow stem cells and an olfactory mucosal graft. Participants were evaluated at the baseline and at 6 monthly intervals. Safety and tolerability were evaluated through the monitoring for adverse events and magnetic resonance imaging evaluation. Efficacy assessment was done through neurological and functional outcome measures.ResultsSurgery was tolerated well by all participants. No significant difference in the ASIA score was observed, although differences in the Functional Independence Measure and Modified Ashworth Scale were statistically significant. No significant complication was observed in any of our patients, except for neurogenic pain in one participant. The follow-up magnetic resonance imaging evaluation revealed an increase in the length of myelomalacia in seven participants.ConclusionsThe cotransplantation of bone marrow stem cells and olfactory mucosa is a safe, feasible and viable procedure in AIS A participants with thoracic level injuries, as assessed at the 24-month follow-up. No efficacy could be demonstrated. For application, further large-scale multicenter studies are needed.

Consensus of clinical neurorestorative progress in patients with complete chronic spinal cord injury.

Currently, there is a lack of effective therapeutic methods to restore neurological function for chronic complete spinal cord injury (SCI) by conventional treatment. Neurorestorative strategies with positive preclinical results have been translated to the clinic, and some patients have gotten benefits and their quality of life has improved. These strategies include cell therapy, neurostimulation or neuromodulation, neuroprosthesis, neurotization or nerve bridging, and neurorehabilitation. The aim of this consensus by 31 experts from 20 countries is to show the objective evidence of clinical neurorestoration for chronic complete SCI by the mentioned neurorestorative strategies. Complete chronic SCI patients are no longer told, "nothing can be done." The clinical translation of more effective preclinical neurorestorative strategies should be encouraged as fast as possible in order to benefit patients with incurable CNS diseases. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Loss of Acquired Functions Due to Thyroid Function Disorder in a Patient with Spinal Cord Injury

The metabolic responses to spinal cord injury (SCI) involve every organ and tissue of the body and yet, surprisingly, little is known about the underlying mechanisms. Many factors are known to affect levels of circulating thyroid hormones such as activity level, nutritional status, systemic illness, drugs, age and trauma. Even healthy person requisited to the bedrest, the normal circadian variation in T3 and T4 may be disappeared. So any condition of traumatic stress will be associated with changes in serum thyroid hormone levels that have been referred to as several syndromes. During chronic disease processes, the state of stress results in hypermetabolism, increased energy expenditure, hyperglycemia and muscle loss. It is anticipated that appropriate metabolic support could improve the outcome in these patients, but considerable controversy remains regarding the indicated therapeutic approach. In patients with SCI, regression or loss of existing functions can be monitored in patients in frequently developed situations due to metabolic problems such as heterotopic ossification, urinary tract infections, deep vein thrombosis, pressure ulcers, neuropathic pain, psychological problems and thyroid dysfunction. In this report we present a chronic SCI patient admitted to the clinic with the chief complaint of loss of the functional status who was diagnosed as a thyroid dysfunction.

Effectiveness of Bisphosphonate Analogues and Functional Electrical Stimulation on Attenuating Post-Injury Osteoporosis in Spinal Cord Injury Patients- a Systematic Review and Meta-Analysis

BackgroundVarious pharmacologic and non-pharmacologic approaches have been applied to reduce sublesional bone loss after spinal cord injury (SCI), and the results are inconsistent across the studies. The objective of this meta-analysis was to investigate whether the two most-studied interventions, bisphosphonate analogues and functional electrical stimulation (FES), could effectively decrease bone mineral density (BMD) attenuation and/or restore lost BMD in the SCI population. MethodsRandomized controlled trials, quasi-experimental studies, and prospective follow-up studies employing bisphosphonates or FES to treat post-SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was the percentage of BMD change from baseline measured by dual-energy X-ray absorptiometry (DEXA) or computed tomography (CT). Data were extracted from four points: the 3rd, 6th, 12th, and 18th month after intervention. ResultsA total of 19 studies were included in the analysis and involved 364 patients and 14 healthy individuals. Acute SCI participants treated with bisphosphonate therapy demonstrated a trend toward less bone loss than participants who received placebos or usual care. A significant difference in BMD decline was noted between both groups at the 3rd and 12th month post-medication. The subgroup analysis failed to show the superiority of intravenous bisphosphonate over oral administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI, 2.08% to 9.84%), 7.21% (95%CI, 1.79% to 12.62%), and 9.56% (95% CI, 2.86% to 16.26%) increases in BMD at the 3rd, 6th, and 12th months post-treatment, respectively. The studies employing FES ≥5 days per week were likely to have better effectiveness than studies using FES ≤3 days per week. ConclusionsOur meta-analysis indicated bisphosphonate administration early following SCI effectively attenuated sublesional bone loss. FES intervention for chronic SCI patients could significantly increase sublesional BMD near the site of maximal mechanical loading.

Improved motor performance in chronic spinal cord injury following upper-limb robotic training

Recovering upper-limb motor function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI). To evaluate the feasibility, safety and effectiveness of robotic-assisted training of upper limb in a chronic SCI population. A total of 10 chronic tetraplegic SCI patients (C4 to C6 level of injury, American Spinal Injury Association Impairment Scale, A to D) participated in a 6-week wrist-robot training protocol (1 hour/day 3 times/week). The following outcome measures were recorded at baseline and after the robotic training: a) motor performance, assessed by robot-measured kinematics, b) corticospinal excitability measured by transcranial magnetic stimulation (TMS), and c) changes in clinical scales: motor strength (Upper extremity motor score), pain level (Visual Analog Scale) and spasticity (Modified Ashworth scale). No adverse effects were observed during or after the robotic training. Statistically significant improvements were found in motor performance kinematics: aim (pre 1.17 ± 0.11 raduans, post 1.03 ± 0.08 raduans, p = 0.03) and smoothness of movement (pre 0.26 ± 0.03, post 0.31 ± 0.02, p = 0.03). These changes were not accompanied by changes in upper-extremity muscle strength or corticospinal excitability. No changes in pain or spasticity were found. Robotic-assisted training of the upper limb over six weeks is a feasible and safe intervention that can enhance movement kinematics without negatively affecting pain or spasticity in chronic SCI. In addition, robot-assisted devices are an excellent tool to quantify motor performance (kinematics) and can be used to sensitively measure changes after a given rehabilitative intervention.

Therapeutic Activities of Engrafted Neural Stem/Precursor Cells Are Not Dormant in the Chronically Injured Spinal Cord

The transplantation of neural stem/precursor cells (NSPCs) is a promising therapeutic strategy for many neurodegenerative disorders including spinal cord injury (SCI) because it provides for neural replacement or trophic support. This strategy is now being extended to the treatment of chronic SCI patients. However, understanding of biological properties of chronically transplanted NSPCs and their surrounding environments is limited. Here, we performed temporal analysis of injured spinal cords and demonstrated their multiphasic cellular and molecular responses. In particular, chronically injured spinal cords were growth factor-enriched environments, whereas acutely injured spinal cords were enriched by neurotrophic and inflammatory factors. To determine how these environmental differences affect engrafted cells, NSPCs transplanted into acutely, subacutely, and chronically injured spinal cords were selectively isolated by flow cytometry, and their whole transcriptomes were compared by RNA sequencing. This analysis revealed that NSPCs produced many regenerative/neurotrophic molecules irrespective of transplantation timing, and these activities were prominent in chronically transplanted NSPCs. Furthermore, chronically injured spinal cords permitted engrafted NSPCs to differentiate into neurons/oligodendrocytes and provided more neurogenic environment for NSPCs than other environments. Despite these results demonstrate that transplanted NSPCs have adequate capacity in generating neurons/oligodendrocytes and producing therapeutic molecules in chronic SCI microenvironments, they did not improve locomotor function. Our results indicate that failure in chronic transplantation is not due to the lack of therapeutic activities of engrafted NSPCs but the refractory state of chronically injured spinal cords. Environmental modulation, rather modification of transplanting cells, will be significant for successful translation of stem cell-based therapies into chronic SCI patients.

Role of Autologous Bone Marrow Mononuclear Cells in Chronic Cervical Spinal Cord Injury-A Longterm Follow Up Study

Spinal cord injury often results into severe neurological deficits. Currently, there is no treatment available which can reverse the damage. Cell transplantation is a novel treatment strategy which has shown promising results in animal models of spinal cord injury. We administered fifty six chronic cervical spinal cord injury patients with autologous bone marrow mononuclear cells, intrathecally. As a part of the protocol, all the patients also underwent rehabilitation along with cell transplantation. On a mean follow up of 2 years ± 1 month, symptoms such as trunk stability, sitting balance, trunk muscle strength, upper limb strength, standing balance, deep touch sensation, bladder sensation, spasticity and walking balance demonstrated improvements. On performing McNemars test, a significant association was found between the improvements in these symptoms and the intervention. The improvement in Functional Independence Measure (FIM) scores was statistically significant using Wilcoxon Signed Rank test. A detailed analysis of factors such as age, cause of injury, chronicity of injury and rehabilitation before the intervention was performed. Here, we also compare this chronic cervical SCI group with chronic thoracolumbar SCI patients of our previous study. Though functional improvements were observed at greater extent in chronic thoracolumbar SCI group, the results in chronic cervical SCI group were also significant. Cell transplantation may promote neurofunctional recovery and improve the quality of life of the patients with chronic cervical spinal cord injury.

Effects of Intravascular Laser Irradiation of Blood in Mitochondria Dysfunction and Oxidative Stress in Adults with Chronic Spinal Cord Injury

This study investigated the clinical effects of intravascular laser irradiation of blood (ILIB) therapy on oxidative stress and mitochondrial dysfunction in subjects with chronic spinal cord injury (SCI) resulting from trauma. Little is known about how ILIB may generate antioxidant defenses in humans, and there is still a lack of randomized, sham-control studies to indicate its influence on different metabolic pathways. Twenty-four chronic SCI subjects (assigned to a sham and a study group), and 12 normal subjects were recruited. The study group underwent 1 h daily of ILIB for 15 days over 3 weeks. The sham group underwent ILIB with no laser power. Baseline measurements established higher oxidative stress and mitochondrial dysfunction in the SCI subjects than in the normal subjects. At day 15 of therapy, the study group revealed a significantly higher mitochondrial DNA (mtDNA) copy number, white blood cell adenosine triphosphate (WBC ATP) synthesis, and total antioxidant capacity (TAC) with significantly reduced malondialdehyde (MDA), than did the sham group. The study group intragroup comparison revealed significantly increased mtDNA copy numbers, WBC ATP synthesis, and TAC, with significantly reduced MDA, compared with its baseline measurements. The sham group intragroup comparisons demonstrated no statistical differences. Low-density lipoprotein (LDL) in the study group was significantly reduced at days 10 and 15, with significantly higher high-density lipoprotein (HDL) at day 45. Our study results contribute to the knowledge about the effectiveness of ILIB in alleviating oxidative stress and mitochondrial dysfunction in chronic SCI patients.

70th Birthday symposium of Prof. Dr. Riederer: autologous adult stem cells in ischemic and traumatic CNS disorders

Ischemic and traumatic insults of the central nervous system both result in definite chronic disability, only to some extent responsive to rehabilitation. Recently, the application of autologous stem cells (fresh bone marrow-derived mononuclear cells including mesenchymal and hematopoietic stem cells) was suggested to provide a strategy to further improve neurological recovery in these disorders. During the acute phase, stem cells act mainly by neuroprotection with prevention of apoptosis, whereas during the chronic situation they provide neurorestoration by transdifferentiation and/or the secretion of neurotrophic factors. To reach these goals, in the acute phase, stem cells (10 million mononuclear cells per kg body weight) might be best applied intravenously, as during the first 7 days after the lesion, the blood-brain barrier permits passage of cells from the blood into the brain or the spinal cord. In the more chronic situation, though, those cells might be applied best intrathecally by lumbar puncture. Based on the reported results so far, it seems justified to develop well-designed clinical double-blind trials in chronic spinal cord injury and ischemic stroke patients, as efficacy and safety concerns might not be answered by preclinical studies.

A Hebbian Approach to Retraining Spared Circuits after Spinal Cord Injury (P02.005)

Objective: 1) Characterize spared neural circuitry after spinal cord injury; 2) Determine efficacy of Hebbian exercises targeting neural circuits above the injury level. Background Spinal cord injury (SCI) only rarely causes complete cord transection. Even patients without volitional movement below a lesion often retain some intact circuitry. The fibers most likely to withstand SCI originate in the brainstem, which generally does not mediate conscious movement. To reestablish conscious control over spared circuits, treatments must strengthen connections between brainstem circuits and volitional corticospinal pathways ABOVE the injury. Using a Hebbian approach of 9Fire Together, Wire Together9, we plan to strengthen these connections with exercises that stimulate both cortical and brainstem pathways simultaneously. We have demonstrated the efficacy of this approach in a rodent SCI model (Harel et al., 2010). We now show further preclinical evidence for efficacy, and introduce a clinical study translating this strategy toward human SCI patients. Design/Methods: PRECLINICAL EXPERIMENTS: To extend our previous results, we compared efficacy of dual-mode (brainstem+corticospinal) to single-mode training in a unilateral pyramidotomy model. Multiple behavioral and histological outcomes were assessed. PLANNED CLINICAL STUDY: Chronic thoracic SCI patients are evaluated with a clinical-neurophysiological testing battery including computerized posturography, motor and sensory evoked potentials, and poly-electromyography. Motor-incomplete subjects are randomized into three groups: 1)treadmill training (spinal); 2)balance training (brainstem); or 3)dual-mode training (balance plus corticospinal hand exercises). Primary outcomes: Gait disability; MEP amplitudes at L4 and S1. Results: PRECLINICAL EXPERIMENTS: In mice with unilateral pyramidotomy, dual-mode but not single-mode exercise significantly improved skilled ladder climbing and several principal components of gait kinematics. Histological assessments of CST fiber sprouting will be presented. BASELINE CLINICAL MEASUREMENTS: Initial results of seated computerized posturography, evoked potentials, and poly-electromyography will be presented. Conclusions: Dual-mode exercise rehabilitation targeting cortical and brainstem pathways ABOVE spinal lesions improves outcomes in animal models of SCI. This rehabilitation approach is feasible for application toward human SCI patients. Supported by: NINDS K08NS056212. NINDS R01NS33020. Falk Medical Research Trust. Department of Veterans Affairs RR&D National Center of Excellence for the Medical Consequences of Spinal Cord Injury (#B4162-C). Disclosure: Dr. Harel has received personal compensation for activities with AlphaDetail and Beebe & O9Neil as a consultant. Dr. Song has nothing to disclose. Dr. Tang has nothing to disclose. Dr. Spungen has nothing to disclose. Dr. Strittmatter has received personal compensation for activities with Biogen Idec. Dr. Strittmatter has received royalty payments from Axerion Therapeutics. Dr. Strittmatter holds stock and/or stock options in Axerion Therapeutics. Dr. Strittmatter has received research support from Axerion Therapeutics.

Sigmoid compliance and visceral perception in spinal cord injury patients

Intestinal motor and sensory dysfunctions in traumatic complete or incomplete spinal cord injury (SCI) are frequent and result in altered mechanisms of defecation. The aim of this study is to investigate sigmoid compliance and perception in chronic SCI patients. Sigmoid responses to fixed-tension distentions were assessed using a tensostat in six patients (six men, 42 ± 4 years) with chronic complete transection of the spinal cord (high-SCI; five tetraplegic C5-C7 and one paraplegic T4-T6) and impaired evacuation (i.e. constipation). A group of 10 healthy individuals (six men, 25 ± 1 years) served as controls. SCI patients had higher sigmoid compliance at the highest distention level than the controls (10.3 ± 2.4 vs. 5.1 ± 0.8 ml/mmHg; P<0.05). Perception scores at first sensation were higher in SCI patients (2.3 ± 0.7 vs. 1.1 ± 0.1; P<0.05), but were not different at the highest distention levels (3.7 ± 0.8 vs. 3 ± 1; NS). The most commonly reported sensation by patients was distention/bloating and was referred less commonly to the hypogastrium compared with distention/bloating in controls. An increased sigmoid compliance can be detected in constipated SCI patients. The preservation of some degree of visceral sensations, although abnormally referred, could imply the occurrence of sensory input remodeling at the spinal level.

Locomotor programs versus ‘conventional’ physical therapy? Locomotor training

In a recent editorial,1 the authors regret that locomotor programs for people with spinal cord injury (SCI) increasingly replace ‘standard physical therapy’, which leads to deficits in mobility and independence of patients using the wheelchair. This generalisation in the absence of references to the literature ignores the many positive effects of properly performed specific locomotor training on a treadmill (Laufband (LB) therapy) as originally suggested for clinical practice by Barbeau's and our group.2, 3 True, in contrast to previous strategies that focused on mobility in the wheelchair, our goal has been first to bring every single patient to his personal optimum in independent upright locomotion (without abandoning wheelchair training).3 ‘Context and activity-related learning’ demanded intensive training of upright walking with rules for limb setting, best practised on a treadmill with a harness allowing body-weight support (BWS). In a study with historical controls and the identical in- and exclusion parameters, LB therapy achieved strikingly better results for acute and chronic SCI patients than any conventional physiotherapy practiced at that time.3 Most important was the high number of originally wheelchair bound SCI patients to become able to stand up without foreign help and walk for short distances, often including walking staircases. Obviously, patients had objectively become more independent. These new abilities were maintained when tested years later.

The Incidence of Venous Thromboembolism in Postoperative Plastic and Reconstructive Surgery Patients with Chronic Spinal Cord Injury

The purpose of this study was to investigate the incidence of postoperative venous thromboembolism in chronic spinal cord injury patients undergoing plastic and reconstructive surgery. Previous studies show a venous thromboembolism incidence of 9.3 percent; however, based on anecdotal evidence, the authors hypothesize that the incidence is actually much lower. As postoperative venous thromboembolism prophylaxis is becoming mandated by the Surgical Care Improvement Project, more data are necessary so that recommendations for chronic spinal cord injury patients can be given. A retrospective chart review was undertaken using electronic medical records from a Veterans Affairs hospital from 2004 through 2009 in which the perioperative course of the chronic spinal cord injury cohort was evaluated for the primary endpoint of venous thromboembolism evolution. The Pearson correlation was used for statistical analysis. Of the 415 operative cases evaluated, 155 cases were excluded secondary to operative time under 1 hour, use of mechanical or chemical venous thromboembolism prophylaxis, unknown operative time, or unknown prophylaxis use. Of the 260 cases evaluated without venous thromboembolism prophylaxis, there were no cases where venous thromboembolism developed within a 2-month postoperative time period. Postoperative venous thromboembolism is a common surgical complication with significant morbidity and mortality. This study demonstrates that in the chronic spinal cord injury patient cohort, the incidence of postoperative venous thromboembolism evolution is extremely low and that a benefit from perioperative mechanical or chemical prophylaxis is not evidence based. Further prospective studies are required to fully elucidate the true venous thromboembolism incidence in these patients and give recommendations on this issue. Therapeutic, IV.

Changes in the structural and material properties of the tibia in patients with spinal cord injury

A cross-sectional study. To measure the change of structural and material properties at different sites of the tibia in spinal cord-injured patients using peripheral quantitative computerised tomography (pQCT). Orthopaedic research centre (UK). Thirty-one subjects were measured--eight with acute spinal cord injury (SCI), nine with chronic SCI and fourteen able-bodied controls. pQCT scans were performed at 2% (proximal), 34% (diaphyseal) and 96% (distal) along the tibia from the tibial plateau. Structural measures of bone were calculated, and volumetric bone mineral density (vBMD) was also measured at all three levels. Muscle cross-sectional area was measured at the diaphyseal level. Structurally, there were changes in the cortical bone; in the diaphysis, the shape of the cross-section changed to offer less resistance to AP bending, and the cross-sectional area of the cortical shell decreased both proximally and distally. There were corresponding changes in vBMD in the anterior aspect of the cortical diaphysis, as well as proximal and distal trabecular bone. Changes in muscle occurred more rapidly than changes in bone. There were clear changes of both structure and material at all three levels of the tibia in chronic SCI patients. These changes were consistent with specific adaptations to reduced local mechanical loading conditions. To assess fracture risk in SCI and also to monitor the effect of therapeutic interventions, the structure of the bone should be considered in addition to trabecular bone mineral density.

Management of bowel dysfunction in the community after spinal cord injury: a postal survey in the Republic of Korea

A cross-sectional postal survey. To describe defecation stimulation methods and their outcomes, and to investigate the impact of bowel dysfunction on the quality of life (QoL) in community-dwelling persons with spinal cord injury in South Korea. Community-based, Korea. A cross-sectional postal survey was conducted. Questionnaires were sent to 459 chronic spinal cord injury (SCI) patients who were registered as members of the Korean Spinal Cord Injury Association. Defecation stimulation methods and their outcomes, the impact of bowel dysfunction on the QoL were investigated. A total of 388 subjects (44.5±10.8 year of age; men, 76.0%; duration of time since the onset of SCI, 14.2±9.5 years) responded. Bowel-related general, social and home QoL deterioration was found in >60%. Suppositories (Supp) were most frequently used, followed by digital rectal stimulation (DRS). The mini enema (ME), which is exclusively used in Korea, was utilized in 18.8%. A defecation time of 30 min was more frequently reported in patients who stimulated defecation with Supp than in those who used DRS. The use of MEs and warm-water irrigations were newly identified in Korea. Bowel care-related factors that greatly deteriorate the QoL were fecal incontinence, time in one defecation >60 min, perianal skin problem, flatus incontinence and hemorrhoids. Alleviating these factors might help to improve the QoL. In particular, stimulation methods to reduce time for defecation might be recommended to persons with chronic SCI.

Long-term follow-up study of outcomes of bladder management in spinal cord injury patients under the care of The Midlands Centre for Spinal Injuries in Oswestry

Retrospective longitudinal study of short- and long-term urinary complications in chronic spinal cord injury (SCI) patients managed at the Midlands Centre for Spinal Injuries (MCSI). MCSI, Oswestry, UK. A total of 185 SCI patients were admitted to the MCSI between 1984 and 1989. Only 119 patients who met the following criteria were included: traumatic SCI, Frankel grade A-D, admission within 6 weeks post injury, regular annual follow-up or alternate year at MCSI, follow-up longer than 8 years. Follow-up ranged between 8 and 21 years with a mean of 17.7 (s.d.=1.98). The method of bladder drainage varied from the time of injury. Drainage was by indwelling urethral catheterisation (IndUC) before admission to the MCSI. Within 24 h of admission, assisted clean intermittent catheterisation (ACIC) by the nursing staff was commenced. This was followed by clean intermittent self catheterisation (CISC) once the patient was mobilised in the wheel chair and trained in the procedure. When detrusor reflex activity develops, patients with good hand function were given a choice between CISC and reflex voiding (RV). Patients with poor hand function are given the choice between RV, suprapubic catheters or ACIC during hospitalisation and after discharge. Only a minority of these patients choose ACIC following discharge. RV was supplemented occasionally by sphincterotomy. There were 99 males and 20 females (5:1). The age at the time of injury was 16-63 years with a mean of 29 (s.d.=12). Instead of a single method, a pattern of bladder management was analysed in the context of three continuous phases: Phase1 preadmission to MCSI. Phase2 during first hospitalisation at MCSI. Phase3 post discharge. In each phase, the patients were divided into those with and without complications. The complications were analysed in relation to the management and other relevant factors. The total complication rate at all stages was 62%. Complications of the upper urinary tract accounted for 22.6%. These results compared favourably with published material. The sequential system of supervised bladder management commencing with brief IndUC followed by IntC and/or RV remains effective in keeping the complication rate relatively low in SCI patients, who undergo regular surveillance and timely intervention. The project was supported by SPIRIT, a charitable not for profit trust that supports teaching, training, clinical research and dissemination of knowledge about all aspects of spinal paralysis in the UK.

Severity of autonomic dysfunction in patients with complete spinal cord injury

There is limited information on the relationship between the level and completeness of the spinal cord injury (SCI) lesion and the degree of autonomic dysfunction. We aimed to study the impairment of sympathetic function in chronic SCI patients presenting with a motor and sensory complete lesion above T6. 26 consecutive traumatic SCI patients were enrolled (14 tetraplegics and 12 paraplegics). They took a battery of tests that included pressor stimuli above (mental arithmetic, hand cold pressor test, sympathetic skin responses (SSR)) and below the lesion (foot cold pressor test, abdominal electrical stimulation), and Valsalva maneuver. All patients showed abolished plantar SSR, while a significant rise in systolic blood pressure in at least one of the pressor tests below the lesion was seen in all but one paraplegic patient. Palmar SSR and blood pressure overshoot at the end of the Valsalva maneuver were abolished in all tetraplegics, whereas at least one of those responses was seen in each paraplegic. Hand cold pressor test and mental arithmetic induced cardiovascular changes in most patients. A complete loss of supraspinal control was observed in all, with a reflex isolated spinal cord in all but one patient. We confirm that in most SCI subjects there is concordance between the impairment of sympathetic function and somatic impairment. To assess autonomic dysfunction, a battery of tests should include SSR, abdominal electrical stimulation and Valsalva maneuver, as they combine pressor stimuli above and below the lesion and assess both cholinergic and sudomotor pathways.

Evaluation of methods to estimate glomerular filtration rate versus actual drug clearance in patients with chronic spinal cord injury

A retrospective chart review. To evaluate different methods of estimating renal function compared with patient-specific vancomycin and aminoglycoside (AG) clearance (CL(DRUG)) in patients with spinal cord injury (SCI), and to develop a new equation to more accurately estimate glomerular filtration rate (GFR) in SCI patients in order to optimize dosing for vancomycin and AG. Veterans Affairs medical center in California, United States of America, tertiary care facility with the largest inpatient SCI center in the VA system. Retrospective data collection from patient records. Pharmacokinetic analysis was performed to obtain actual CL(DRUG,) which is compared with different methods of estimating GFR.A total of 310 patients were initially assessed; however, only 141 patients met the inclusion criteria, had a diagnosis of chronic SCI, and received vancomycin or AG with at least one drug level at steady state from January to December of 2008. All four equations evaluated to estimate GFR significantly overestimated CL(DRUG): the Modification of Diet in Renal Disease equation by 141%, Cockcroft-Gault equation by 83%, Chronic Kidney Disease Epidemiology Collaboration equation by 82% and 24-h endogenous creatinine clearance by 71% (P<0.001). The modified Cockcroft-Gault equation (CL(M)) showed improvement, however, still overestimated CL(DRUG) by 39% (P<0.001). Thus, a new equation for SCI (CL(SCI)) was developed which underestimated CL(DRUG) by <5% (P=0.16). Compared with different methods of estimating GFR, CL(SCI)=2.3 × x (0.7) (x equals CL(M) in ml min(-1)) more accurately estimates CL(DRUG) in chronic SCI patients.

High Doses of 4-Aminopyridine Improve Functionality in Chronic Complete Spinal Cord Injury Patients with MRI Evidence of Cord Continuity

Many patients with complete spinal cord injury (SCI) exhibit demyelinated and poorly myelinated nerve fibers traversing the lesion site. Conventional doses of 4-aminopyridine (4-AP, 30 mg/day) have shown to provide no or minor functional improvement in these patients. We undertook this study to test the functional effect of high doses of 4-AP on patients with chronic complete SCI with cord continuity at the site of injury demonstrated by magnetic resonance imaging. Fourteen patients were included in a double-blind, randomized, placebo-controlled trial followed by an open label long-term follow-up. Initially, patients received 4-AP or placebo orally, with 4-AP being increased gradually (5 mg/week) to reach 30 mg/day. For long-term treatment, 4-AP was increased 10 mg periodically according to negative electroencephalogram and blood test abnormalities and minor adverse reactions. Pre-treatment, 12 and 24 weeks of the controlled trial, and 6 and 12 months of open trial evaluations, or with the highest doses reached were obtained. Three of 12 patients were able to walk with the assistance of orthopedic devices, 1/12 became incomplete (AIS B), 7/12 improved their somatosensory evoked potentials, 5/12 had sensation and control of bladder and anal sphincters, and 4/9 male patients had psychogenic erection. Positive changes were seen mainly in patients with cyst (4/5) or atrophy (3/5) of the injury site. Two patients withdrew from the study: one had seizures and one had intolerant adverse reactions. We conclude that high doses of 4-AP in the studied population produced several functional benefits not observed using lower doses.

*Poster 47: Correlations Between Recovery of Ambulatory Capacity and Lower-Limb Somatosensory Evoked Potentials in Incomplete Spinal Cord Injury

Objective: To study relationships between posterior tibial (PT) nerve somatosensory evoked potentials (SEP) and recovery of ambulatory capacity in patients with incomplete spinal cord injury (SCI) participating in Lokomat training. Design: Correlation study of functional clinical outcome with quantitative electrophysiological measures of sensory processing. Setting: Queen Elizabeth National Spinal Injuries Unit, Scotland. Participants: 13 acute and 5 chronic incomplete SCI patients. Intervention: 30 hours Lokomat Training over a 6-week period.