Lack of improvement in anorectal manometry parameters after implementation of a pelvic floor/anal sphincter biofeedback in persons with motor-incomplete spinal cord injury.

BACKGROUND: Effect of biofeedback on improving anorectal manometric parameters in incomplete spinal cord injury is unknown. A short-term biofeedback program investigated any effect on anorectal manometric parameters without correlation to bowel symptoms. METHODS: This prospective uncontrolled interventional study comprised three study subject groups, Group 1: sensory/motor-complete American Spinal Injury Association Impairment Scale (AIS) A SCI (n = 13); Group 2 (biofeedback group): sensory incomplete AIS B SCI (n = 17) (n = 3), and motor-incomplete AIS C SCI (n = 8), and AIS D SCI (n = 6); and Group 3: able-bodied (AB) controls (n = 12). High-resolution anorectal manometry (HR-ARM) was applied to establish baseline characteristics in all subjects for anorectal pressure, volume, length of pressure zones, and duration of sphincter squeeze pressure. SCI participants with motor-incomplete SCI were enrolled in pelvic floor/anal sphincter bowel biofeedback training (2 × 6-week training periods comprised of two training sessions per week for 30-45 min per session). HR-ARM was also performed after each of the 6-week periods of biofeedback training. RESULTS: Compared to motor-complete or motor-incomplete SCI participants, AB subjects had higher mean intra-rectal pressure, maximal sphincteric pressure, residual anal pressure, recto-anal pressure gradient, and duration of squeeze (p < 0.05 for each of the endpoints). No significant difference was evident at baseline between the motor-complete and motor-incomplete SCI groups. In motor-incomplete SCI subjects, the pelvic floor/anal sphincter biofeedback protocol failed to improve HR-ARM parameters. CONCLUSION: Biofeedback training program did not improve anal manometric parameters in subjects with motor-incomplete or sensory-incomplete SCI. Biofeedback did not change physiology, and its effects on symptoms are unknown. INFERENCES: Utility of biofeedback is limited in patients with incomplete spinal cord injury in terms of improving HR-ARM parameters.

Administration of High-Dose Methylprednisolone Worsens Bone Loss after Acute Spinal Cord Injury in Rats.

The administration of high-dose methylprednisolone (MP) for 24-48 h after traumatic spinal cord injury (SCI) has been shown to improve functional recovery. The known adverse effects of MP on skeletal muscle and the immune system, though, have raised clinically relevant safety concerns. However, the effect of MP administration on SCI-induced bone loss has not been evaluated to date. This study examined the adverse effects of high-dose MP administration on skeletal bone after acute SCI in rodents. Male rats underwent spinal cord transection at T3-T4, which was followed by an intravenous injection of MP and subsequent infusion of MP for 24 h. At 2 days, animals were euthanized and hindlimb bone samples were collected. MP significantly reduced bone mineral density (-6.7%) and induced deterioration of bone microstructure (trabecular bone volume/tissue volume, -18.4%; trabecular number, -19.4%) in the distal femur of SCI rats. MP significantly increased expression in the hindlimb bones of osteoclastic genes receptor activator of nuclear factor-κB ligand (RANKL; +402%), triiodothyronine receptor auxiliary protein (+32%), calcitonin receptor (+41%), and reduced osteoprotegerin/RANKL ratio (-72%) compared to those of SCI-vehicle animals. Collectively, 1 day of high-dose MP at a dose comparable to the dosing regimen prescribed to patients who qualify to receive this treatment approach with acute SCI increased loss of bone mass and integrity below the level of lesion than that of animals that had SCI alone, and was associated with further elevation in the expression of genes involved in pathways associated with osteoclastic bone resorption than that observed in SCI animals.

Abundance in proteins expressed after functional electrical stimulation cycling or arm cycling ergometry training in persons with chronic spinal cord injury.

STUDY DESIGN: Longitudinal design. OBJECTIVES: The study determined the effects of two forms of exercise training on the abundance of two proteins, (glucose transporter-4 [GLUT-4], adenosine monophosphate kinase [AMPK]) involved in glucose utilization and the transcriptional coactivator that regulates the genes involved in energy metabolism and mitochondrial biogenesis (peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha [PGC-1α]), in muscles in men with chronic motor-complete spinal cord injury (SCI). SETTINGS: Clinical trial at a Medical Center. METHODS: Nine men with chronic motor-complete SCI participated in functional electrical stimulation lower extremity cycling (FES-LEC; n = 4) or arm cycling ergometer (arm-cycling ergometer [ACE]; n = 5) 5 days/week for 16 weeks. Whole body composition was measured by dual energy X-ray absorptiometry. An intravenous glucose tolerance test was performed to measure glucose effectiveness (Sg) and insulin sensitivity (Si). Muscle biopsies of the right vastus lateralis (VL) and triceps muscles were collected one week prior to and post the exercise training intervention. RESULTS: Neither training intervention altered body composition or carbohydrate metabolism. GLUT-4 increased by 3.8 fold in the VL after FES training and increased 0.6 fold in the triceps after ACE training. PGC-1α increased by 2.3 fold in the VL after FES training and 3.8 fold in the triceps after ACE training. AMPK increased by 3.4 fold in the VL after FES training and in the triceps after ACE training. CONCLUSION: FES-LEC and ACE training were associated with greater protein expressions in the trained muscles by effectively influencing the abundance of GLUT-4, AMPK and PGC-1α. Thus, FES-LEC training of paralyzed muscle can modulate protein expression similar to that of trained and innervated muscle.

Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection.

BACKGROUND: Spinal cord injury (SCI) results in muscle atrophy and a shift of slow oxidative to fast glycolytic fibers. Electrical stimulation (ES) at least partially restores muscle mass and fiber type distribution. The objective of this study was to was to characterize the early molecular adaptations that occur in rat soleus muscle after initiating isometric resistance exercise by ES for one hour per day for 1, 3 or 7 days when ES was begun 16 weeks after SCI. Additionally, changes in mRNA levels after ES were compared with those induced in soleus at the same time points after gastrocnemius tenotomy (GA). RESULTS: ES increased expression of Hey1 and Pitx2 suggesting increased Notch and Wnt signaling, respectively, but did not normalize RCAN1.4, a measure of calcineurin/NFAT signaling, or PGC-1ß mRNA levels. ES increased PGC-1α expression but not that of slow myofibrillar genes. Microarray analysis showed that after ES, genes coding for calcium binding proteins and nicotinic acetylcholine receptors were increased, and the expression of genes involved in blood vessel formation and morphogenesis was altered. Of the 165 genes altered by ES only 16 were also differentially expressed after GA, of which 12 were altered in the same direction by ES and GA. In contrast to ES, GA induced expression of genes related to oxidative phosphorylation. CONCLUSIONS: Notch and Wnt signaling may be involved in ES-induced increases in the mass of paralyzed muscle. Molecular adaptations of paralyzed soleus to resistance exercise are delayed or defective compared to normally innervated muscle.

An effective oral vitamin D replacement therapy in persons with spinal cord injury.

BACKGROUND/OBJECTIVE: Vitamin D deficiency is prevalent in chronic spinal cord injury (SCI). A 3-month course of oral vitamin D(3) to 'normalize' serum vitamin D levels was investigated. DESIGN: Prospective drug-intervention study. SETTING: VA Medical Center; private rehabilitation facility. METHODS: Seven individuals with chronic SCI and vitamin D deficiency completed 3 months of oral vitamin D(3) (i.e. cholecalciferol) supplementation. At screening, baseline, and months 1 and 3, blood was collected for serum calcium, 25 hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), and N-telopeptide (NTx); 24-hour urine for calcium, creatinine, and NTx was performed. Oral vitamin D(3) (2000 IU daily) and elemental calcium (1.3 g daily) were prescribed for 90 days. The results are expressed as mean ± standard deviation (SD). Analysis of variance with a Fisher's post-hoc analysis was performed to test for differences between study visits. Subjects were classified as deficient (<20 ng/ml), relatively deficient (20-30 ng/ml), or not deficient (>30 ng/ml) in 25(OH)D. RESULTS: Serum 25(OH)D levels were greater at months 1 and 3 than at baseline (26 ± 6 and 48 ± 17 vs. 14 ± 2 ng/ml; P = 0.005). Six of seven subjects were no longer deficient [25(OH)D >30 ng/ml] by month 3. Serum iPTH levels were significantly decreased at month 1 and month 3; serum NTx levels were significantly lower at month 3 than at baseline. Serum and urinary calcium levels remained within the normal range. CONCLUSION: A daily prescription of 2000 IU of oral vitamin D(3) for 3 months safely raised serum 25(OH)D levels into the normal range in persons with chronic SCI on calcium supplementation.

Poor nutrition is a relative contraindication to negative pressure wound therapy for pressure ulcers: preliminary observations in patients with spinal cord injury.

OBJECTIVE: To assess the efficacy of negative-pressure wound therapy (NPWT) for healing of pressure ulcers (PrUs) in individuals with spinal-cord injury (SCI). DESIGN: Multicenter, 28-day observational study. SETTING: Ten Veterans Affairs Medical Center SCI centers. PATIENTS: Eighty-six SCI inpatients with Stage III/IV pelvic PrUs. INTERVENTIONS: Standard wound care with NPWT versus standard wound care alone (NoNPWT). MAIN OUTCOME MEASURES: Change in wound surface area (WSA) using the Verg Videometer Measurement Documentation software. MAIN RESULTS: The proportion of patients demonstrating a decrease in WSA (healing subgroup) was not significantly different between the NPWT (n = 33) and NoNPWT (n = 53) groups (67% vs 70%, respectively). In the healing subgroup, there was no significant difference between the NPWT versus NoNPWT groups in WSA decrease (-43 ± 22% vs -50% ± 26%, not statistically significant). Similarly, in the nonhealing subgroup, there was no significant difference between NPWT and NoNPWT groups (31% ± 26% vs 32% ± 34%). In the NPWT group, the nonhealing subgroup (11/33) had significantly lower serum albumin levels than the healing subgroup (22/33) (2.9 ± 0.4 vs 3.3 ± 0.5 mg/dL, P < .05). In the NoNPWT group, there was no significant difference in serum albumin levels between the healing versus nonhealing subgroups (3.2 ± 0.3 vs 3.2 ± 0.3 mg/dL). CONCLUSION: In SCI patients with Stage III/IV pelvic PrUs, NPWT did not significantly influence the rate of healing. Additionally, in malnourished individuals (albumin <3.0 mg/dL), NPWT was not efficacious. Healing outcomes in the NPWT group were significantly influenced by albumin levels, whereas no such disparity was noted between the healing and nonhealing PrUs for the NoNPWT group. Nutritional status appears to be important in the effectiveness of NPWT.

Evolving concepts in neurogenic osteoporosis.

Convincing evidence has accumulated of regulation of bone by the central nervous system. The neural connection between brain and bone is mediated centrally by classic neurotransmitters and several neuropeptides, and peripherally by many of the same neurotransmitters and neuropeptides, albeit with actions opposite to their central effects. Pharmacologic blockade of ß2-adrenergic receptors or disruption of the gene encoding them increases bone mass, whereas increased activity of the sympathetic nervous system (SNS) contributes to bone loss. Brainstem serotonergic neurons regulate SNS activity and its modulation by leptin. Physiologic stimulation of osteoblastic nicotinic receptors results in proliferation and deposition of bone, whereas higher levels inhibit osteoblast function. Activation of sensory nerves has a centrally mediated action on bone, albeit poorly understood. The relative importance of, and interactions between autonomic, sensory, and peripheral nervous system actions on bone mass are also not clear in healthy individuals, and less so in pathologic states.

Lower-extremity functional electrical stimulation decreases platelet aggregation and blood coagulation in persons with chronic spinal cord injury: a pilot study.

BACKGROUND: Individuals with spinal cord injury (SCI) develop premature cardiovascular disease. Regular exercise reduces the incidence and symptoms of cardiovascular disease in able-bodied individuals; these salutary effects of exercise have not been documented in persons with SCI. OBJECTIVE: To evaluate the effects of functional electrical stimulation leg cycle ergometry (FES-LCE) exercise training on platelet aggregation and blood coagulation in persons with SCI. PARTICIPANTS: Subjects (n=14) with stable chronic (>1 year) paraplegia (T1-T10) or tetraplegia (C4-C8). METHODS: Blood samples were collected before and after the first and eighth sessions (2 sessions per week for 4 weeks) of FES exercise. RESULTS: Platelet aggregation was inhibited by 20% after the first session and by 40% (P < 0.001) after the eighth session. Thrombin activity was unchanged after the first session (10.7 +/- 0.85 s to 10.43 +/- 0.56 s) and decreased after the eighth session (12.5 +/- 1.98 s to 11.1 +/- 1.7 s; P < 0.0003). Antithrombin III activity increased after the first (103.8% +/- 8.9% to 110% +/- 6.9%; P < 0.0008) and eighth sessions (107.8% +/- 12.1% to 120.4% +/- 13.1%; P < 0.0001). Cyclic adenosine monophosphate increased after the first (9.9% + 2.5% to 15.8% +/- 3%; P < 0.001) and eighth sessions (17.8% +/- 4.2% to 36.5% +/- 7.6%; P < 0.0001). After the eighth session, factors V and X increased significantly (88% +/- 27% to 103% +/- 23%, P < 0.0001; 100% +/- 40% to 105% +/- 7%, P < 0.01, respectively); factors VII and VIII and fibrinogen did not change significantly. A significant reduction in platelet activation/aggregation was demonstrated in response to FES-LCE. The decrease in thrombin level was caused by the simultaneous increase in antithrombin activity. CONCLUSION: These findings provide new insight into the potential protective effects of FES-LCE against the risk of cardiovascular disease.

Nandrolone slows hindlimb bone loss in a rat model of bone loss due to denervation.

Nandrolone is an anabolic steroid that has been demonstrated to reduce the loss of bone and muscle from hindlimb unweighting and to slow muscle atrophy after nerve transection. To determine whether nandrolone has the ability to protect bone against loss due to disuse after denervation, male rats underwent sciatic nerve transaction, followed 28 days later by treatment with nandrolone or vehicle for 28 days. Bone mineral density (BMD) was determined 28 days later or 56 days after nerve transection. Denervation led to reductions in BMD of 7% and 12% for femur and tibia, respectively. Nandrolone preserved 80% and 60% of BMD in femur and tibia, respectively, demonstrating that nandrolone administration significantly reduced loss of BMD from denervation. This study offers a potential novel pharmacological strategy for use of nandrolone to reduce bone loss in severe disuse- and denervation-related bone loss, such as that which occurs after spinal cord injury.

Vitamin D replacement therapy in persons with spinal cord injury.

BACKGROUND/OBJECTIVE: An increased prevalence of vitamin D deficiency has been reported in persons with chronic spinal cord injury (SCI), but treatment guidelines for replacement are not available. The purpose of this study was to evaluate two types of vitamin D therapy on calcium metabolism and vitamin D status in persons with SCI. METHODS: Ten subjects with chronic SCI who were vitamin D deficient received 25 hydroxyvitamin D3 [25(OH)D], 50 microg twice a week, for 14 days (Study 1). Regardless of vitamin D status, 40 subjects received vitamin D3 800 IU (20 microg) daily for 12 months (Study 2). Supplemental calcium was administered. The response to therapy was determined by the effect upon serum 25(OH)D levels. Results are expressed as mean +/- standard deviation. RESULTS: In Study 1, serum 25(OH)D levels increased by day 14 (8.7 +/- 2.1 vs 14.7 +/- 3.6 ng/mL; P < 0.0005). However, in 8 of 10 subjects, 25(OH)D levels were still below the absolute lower limit of normal. Serum calcium levels were not significantly different, but urinary calcium excretion increased (103 +/- 81 vs 184 +/- 145 mg/d; P < 0.01). Serum parathyroid hormone (PTH) levels decreased (35 +/- 26 vs 1 7 +/- 12 pg/ mL; P < 0.01). In Study 2, after 12 months of vitamin D supplementation, 9 subjects had an absolute and 23 had a relative vitamin D deficiency, compared with 33 and 6 subjects, respectively, at baseline. By 12 months, the 25(OH)D level increased (10.7 +/- 7.1 to 22.5 +/- 7.5 ng/mL; P < 0.0001) and the serum PTH level decreased (37 +/- 16 vs 25 +/- 11 pg/mL; P < 0.0001). CONCLUSIONS: Although 25(OH)D levels significantly increased in both studies, the replacement therapies employed were not sufficient to recommend for adoption for clinical use, indicating the need for higher doses and/or for longer periods of administration.