Dysfunction In Spinal Cord Injury Patients Research Articles

Quantitative analysis of dysautonomia in patients with autonomic dysreflexia.

Autonomic dysreflexia (AD) is a life-threatening condition for individuals with cervical or high-thoracic spinal cord injury (SCI). The profile of autonomic dysfunction in AD using validated clinical autonomic tests has not been described so far, although it could be useful to identify SCI patients at greater risk of developing AD non-invasively. With this objective, 37 SCI patients (27% female) were recruited, and hemodynamic and cardiac parameters were continuously monitored to determine the presence of AD, defined as an increase of systolic blood pressure of 20mmHg or higher after bladder filling with saline. Then, standard autonomic function testing was performed, including Deep Breathing, Valsalva Manoeuvre and Tilt Table Test. Finally, baroreflex sensitivity (BRS), and spectral analysis of heart rate and blood pressure variability were measured at rest. Catecholamines and vasopressin levels were also measured at supine and upright positions. The severity of SCI was assessed through clinical and radiological examinations. AD was observed in 73.3% of SCI patients, being 63.6% of them asymptomatic during the dysreflexive episode. AD patients displayed a drop in sympathetic outflow, as determined by decreased noradrenalin plasma levels, reduced sympathovagal balance and increased BRS. In line with decreased sympathetic activity, the incidence of neurogenic orthostatic hypotension was higher in AD patients. Our results provide novel evidence regarding the autonomic dysfunction in SCI patients with AD compared to non-AD patients, posing non-invasively measured autonomic parameters as a powerful clinical tool to predict AD in SCI patients.

Inhibition of NOX2 signaling limits pain-related behavior and improves motor function in male mice after spinal cord injury: Participation of IL-10/miR-155 pathways

NADPH oxidase (NOX2) is an enzyme that induces reactive oxygen species (ROS) and serves as a switch between the pro-inflammatory and neurorestorative microglial/macrophage phenotypes; such changes play an important role in neuropathic pain and motor dysfunction. Increased NOX2 expression after spinal cord injury (SCI) has been reported, and inhibition of NOX2 improves motor function. However, the underlying mechanisms of NOX2 in post-traumatic pain and motor deficit remain unexplored. In the present study, we report that depletion of NOX2 (NOX2−/−) or inhibition of NOX2 using NOX2ds-tat significantly reduced mechanical/thermal cutaneous hypersensitivity and motor dysfunction after moderate contusion SCI at T10 in male mice. Western blot (WB, 3 mm lesion area) and immunohistochemistry (IHC) showed that SCI elevates NOX2 expression predominantly in microglia/macrophages up to 8 weeks post-injury. Deletion of NOX2 significantly reduced CD11b+/CD45hiF4/80+ macrophage infiltration at 24 h post-injury detected by flow cytometry and 8-OHG+ ROS production at 8 weeks post-injury by IHC in both lesion area and lumbar enlargement. NOX2 deficiency also altered microglial/macrophage pro-inflammatory and anti-inflammatory balance towards the neurorestorative response. WB analysis showed robust increase of Arginase-1 and YM1 proteins in NOX2−/− mice. Furthermore, qPCR analysis showed significant up-regulation of anti-inflammatory cytokine IL-10 levels in NOX2−/− mice, associated with reduced microRNA-155 expression. These findings were confirmed in CD11b+ microglia/macrophages isolated from spinal cord at 3 days post-injury. Taken together, our data suggest an important role for IL-10/miR-155 pathway in regulating NOX2-mediated SCI-dysfunction. Thus, specific targeting of NOX2 may provide an effective strategy for treating neurological dysfunction in SCI patients.

Impaired Baroreflex Function during Orthostatic Challenge in Patients after Spinal Cord Injury.

The level of spinal cord injury (SCI) affects baroreflex regulation of blood pressure. While a parasympathetic cardiac chronotropic effect is preserved, baroreflex response could be impaired by sympathetic dysfunction under the SCI level. This study was aimed to evaluate the baroreflex function in SCI patients by the analysis of causal interaction between systolic blood pressure (SBP) and inter-beat intervals (IBI). Blood pressure was continuously recorded in 13 cervical SCI patients (CSCI), nine thoracic SCI (ThSCI) and 13 able-bodied controls (Con) during two phases: sitting (PS) and orthostatic challenge (PO). Beat-to-beat SBP and IBI sequences were obtained from continuous blood pressure recording. Closed loop of SBP-IBI interaction was mathematically opened by bivariate autoregressive model; causal coherence and baroreflex sensitivity (BRS) were calculated in baroreflex direction. Coherence quantifies causal synchronicity between SBP and IBI. The gain of transfer function from SBP to IBI represents BRS. PS (medians of CSCI/ThSCI/Con) coherence was 0.28/0.33/0.25 (no significant difference) and PS BRS was 6.98/7.54/6.66 (no difference). PO coherence was 0.18/0.58/0.45 (CSCI < ThCSI and Con; p < 0.01) and PO BRS was 2.38/5.87/6.22 (CSCI < ThCSI and Con; p < 0.01). For position change effect, there was no change in CSCI coherence; for ThSCI and Con, PS < PO (p < 0.05). For BRS in the CSCI group, PS < PO (p < 0.01); for ThSCI and Con, there was no change. BRS and coherence correlated negatively with SCI level (p < 0.01). In conclusion, baroreflex dysfunction in SCI patients was detected using causal analysis methods during orthostatic challenge only. Baroreflex dysfunction is probably an important mechanism of the more expressed blood pressure decrease associated with CSCI. The severity of autonomic dysfunction was related to SCI level.

The effect of the 5‐HT7 serotonin receptor agonist, LP44, on micturition in rats with chronic spinal cord injury

To better understand the effects of the selective 5-HT7 receptor agonist 4-[2-(Methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-piperazinehexanamide hydrochloride (LP44) on micturition in spinal cord injury (SCI) rats. Female Sprague-Dawley rats weighing 200-275 g were used. SCI was produced in 8 of the 16 rats by transection at the T10 level; cystometric study occurred 8-12 weeks post-transection. Intravesical pressure was monitored in urethane-anesthetized animals via a transvesical catheter. The selective 5-HT7 antagonist (R)-3-[2-[2-(4-Methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl] phenol hydrochloride (SB-269970) was administered after each LP44 dose-response curve (all drugs were administered intravenously, i.v). Compared to controls, SCI rats had a higher bladder capacity and residual volume, and a lower voiding efficiency. In SCI rats, LP44 (0.003-0.3 mg/kg, i.v) induced significant dose-dependent increases in micturition volume, significant dose-dependent decreases in residual volume, resulting in significant increases in voiding efficiency. CMG measurements showed a dose-dependent increase of the high-frequency oscillation (HFO) activity, including the number of small oscillation per voiding. This was correlated with the improved voiding efficiency. SB-269970 (0.1 mg/kg, i.v) partially or completely reversed all LP44-induced changes. HFOs seems to be correlated with external urethral sphincter (EUS) bursting activity during voiding. Both the bladder voiding efficiency and the periodic EUS activity were decreased in SCI rats. 5-HT7 receptor agonist can enhance HFO activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding dysfunction in SCI patients remains to be studied.

Lack of improvement after audit assessing the management of voiding dysfunction in patients with spinal cord injury: Necessity for institutional guidelines

Introduction Standard management guidelines for voiding dysfunction in patients with spinal cord injury (SCI) do not exist and these patients are managed on the basis of institutional protocols or individual judgment of managing physicians. Objectives To notice general trends and improvements over a five-year period, in the institutional practices related to management of voiding dysfunction in SCI patients. Methodology A retrospective cross-sectional study was conducted by Neurosurgery and Urology services together. A nine years (June 1995–June 2004) internal clinical audit of urological management of SCI patients was compared with a similar audit conducted five years later (January 2008–June 2010). Comparisons were made using chi-square test. A p-value of <0.05 was considered statistically significant. Results A total of 146 patients were compared (89-pre-audit, 57-post-audit). The quality of documentation of examination findings worsened over the two study periods ( p = 0.002). Although determination of baseline serum creatinine improved to statistically significant levels ( p = 0.019), no imaging for the kidneys was performed as baseline in the post-audit period ( p = 0.000). Similarly the number of urodynamic studies performed decreased from 11% to 1.75% ( p = 0.045). The number of urological consultations, however, increased from 26% to 31.58% ( p = 0.452). During follow-up, only 17 (19.1%) patients in the pre-audit study period and 6 (10.5%) in the post-audit study period were voiding spontaneously. Conclusion Our study of two eras clearly demonstrated a worsening trend in quality of patient management, which can be corrected by agreeing upon and implementing standard guidelines for management of SCI patients.

THE EFFECT OF OXYGEN ON PULMONARY MUSCLE FUNCTION IN PATIENTS WITH SPINAL CORD INJURY

S421 INTRODUCTION: Pulmonary muscle dysfunction is common in Spinal Cord injury (SCI) patients [1] Depending on the level and degree of SCI, respiration may be impaired by paralysis of intercostal, accessory and abdominal muscles. Oxygen therapy has been shown to improve pulmonary function in normal volunteers [2]. The purpose of this study was to see if oxygen therapy might improve the pulmonary function of SCI patients. METHODS: This study was approved by Human Subjects Committee. SCI patients were eligible for study entry. Three groups of patients were studied. Group I - included quadriplegic patients with level of injury C1-C7, Group II - included paraplegic patients with level of injury T1-T7 and Group III - included paraplegic patients with level of injury T8-T12. We measured tidal volume (TV), respiratory rate (RR), labored breathing index (LBI) and oxygen saturation (SaO2) before and after oxygen administration (4L/min) in each patient. Tidal volume was measured using a spirometric flowmeter (Ohmeda 5410). Labored breathing index (LBI), an index of rib cage and abdominal respiratory muscle synchrony, was measured with a Respitrace (non-invasive monitoring system; NIMS; Miami Beach, Fl). The Respitrace uses a respiratory impedance plethysmographic method with two elastic bands, one band is placed around the rib cage (at the nipple line) and the other band is around the abdomen (at the umbilicus). Oxygen saturation was measured with a pulse oximeter (Ohmeda 3700). We evaluated the effect of oxygen on pulmonary function using 2-way ANOVA with post - hoc testing as appropriate. A p < 0.05 was considered statistically significant. RESULTS: Five patients were studied in each group Table 1Table 1A normal LBI is 1.0.; an LBI > 1.3 indicates dys-coordination between abdominal and rib cage respiratory muscles. DISCUSSION: Oxygen therapy significantly improved LBI. Cervical SCI patients had significantly higher LBI than thoracic SCI as measured by LBI and TV. The degree of pulmonary muscle dysfunction in SCI patients varies with the level of injury; the higher the level of injury, the greater the dysfunction. Cervical SCI patients had the worst breathing pattern and smallest TV.

Chronic gastrointestinal problems and bowel dysfunction in patients with spinal cord injury.

Amongst complications arising from spinal cord injury (SCI), chronic gastrointestinal (G-I) problems and bowel dysfunction have not received as much research attention as many other medical and rehabilitation problems, even although their incidence is not negligible. We therefore investigated chronic G-I problems and bowel dysfunction in SCI patients where the degree of these was such that activities of daily living (ADL) were significantly affected and/or long-term medical management was required. Detailed semi-structured individual interviews were conducted with 72 traumatic SCI patients. The history of SCI was longer than 6 months, bowel habits had settled, and neurological recovery was completed. The incidence of chronic G-I problems was very high (62.5%), most were associated with defecation difficulties such as severe constipation, difficult with evacuation, pain associated with defecation, or urgency with incontinence. These problems had an extensive impact on ADL, and in particular, restricted diet (80%), restricted outdoor ambulation (64%) and caused unhappiness with bowel care (62%). Bowel care was performed once per 2.85 +/- 1.96 days and occupied an average of 42.1 +/- 28.7 min. To improve bowel habits, 43% of the patients took oral medication, and 36.1% controlled their diet. The usual methods of bowel care were anal massage (34.7%), unaided self-defecation with or without oral medication and abdominal massage (29.2%), finger enema (18.1%), rectal suppository (15.2%) and in two patients a colostomy tube had been inserted because of rectal cancer and traumatic colorectal injury. These chronic G-I symptoms were vague and very subjective, but significant enough to affect the quality of life. Bowel dysfunction was not related to age, duration of, or the neurological level of injury, ASIA score of ADL level, and bowel habits had generally settled within 6 months of SCI. With regard to frequency, time, and method of defection, bowel care habits varied considerably amongst individuals, and in relation to the extent to which practical results matched the level of expectation generated by physicians' recommended care program. Individual satisfaction was also very subjective. We therefore suggest that during the early stage of rehabilitation, an appropriate bowel program should be properly designed and adequate training provided.