Incident traumatic spinal cord injury and risk of Alzheimer's disease and related dementia: longitudinal case and control cohort study.

STUDY DESIGN: Retrospective case/control longitudinal cohort study OBJECTIVES: Prevalent traumatic spinal cord injury (TSCI) is associated with Alzheimer's disease and related dementia (ADRD). We examined the hazard ratio for ADRD after incident TSCI and hypothesized that ADRD hazard is greater among adults with incident TSCI compared with their matched control of adults without TSCI. SETTING: Using 2010-2020 U.S. national private administrative claims data, we identified adults aged 45 years and older with probable (likely and highly likely) incident TSCI (n = 657). Our controls included one-to-ten matched cohort of people without TSCI (n = 6553). METHODS: We applied Cox survival models and adjusted them for age, sex, years of living with certain chronic conditions, exposure to six classes of prescribed medications, and neighborhood characteristics of place of residence. Hazard ratios were used to compare the results within a 4-year follow-up. RESULTS: Our fully adjusted model without any interaction showed that incident TSCI increased the risk for ADRD (HR = 1.30; 95% CI, 1.01-1.67). People aged 45-64 with incident TSCI were at high risk for ADRD (HR = 5.14; 95% CI, 2.27-11.67) and no significant risk after age 65 (HR = 1.20; 95% CI, .92-1.55). Our sensitivity analyses confirmed a higher hazard ratio for ADRD after incident TSCI at 45-64 years of age compared with the matched controls. CONCLUSIONS: TSCI is associated with a higher hazard of ADRD. This study informs the need to update clinical guidelines for cognitive screening after TSCI to address the heightened risk of cognitive decline and to shed light on the causality between TSCI and ADRD.

Short-Term Dorsal Genital Nerve Stimulation Increases Subjective Arousal in Women With and Without Spinal Cord Injury: A Preliminary Investigation.

OBJECTIVES: Female sexual dysfunction (FSD) affects an estimated 40% of women. Unfortunately, FSD is understudied, leading to limited treatment options for FSD. Neuromodulation has shown some success in alleviating FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD. MATERIALS AND METHODS: This study comprises a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations. RESULTS: We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations. CONCLUSIONS: To our knowledge, this is the first study to measure sexual arousal in response to short-term neuromodulation in women. This study indicates that short-term DGNS but not TNS can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for FSD.

Acute dorsal genital nerve stimulation increases subjective arousal in women with and without spinal cord injury: a preliminary investigation.

Introduction: Female sexual dysfunction (FSD) impacts an estimated 40% of women. Unfortunately, female sexual function is understudied, leading to limited treatment options for FSD. Neuromodulation has demonstrated some success in improving FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD. Methods: This study consists of a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations. Results: We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations. Discussion: This is the first study to measure sexual arousal in response to acute neuromodulation in women. This study demonstrates that acute DGNS, but not TNS, can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for female sexual dysfunction.

Factors influencing decisions about neurogenic bladder and bowel surgeries among veterans and civilians with spinal cord injury.

OBJECTIVE: This study investigated factors influencing surgical decision-making (DM) to treat neurogenic bladder and bowel (NBB) dysfunction for veterans and civilians with spinal cord injury (SCI) in the United States (US). DESIGN: Semi-structured interviews complemented by survey measures. SETTING: Community-dwelling participants who received treatment at a major Midwestern US medical system, a nearby Veterans Affairs (VA) facility, and other VA sites around the US. PARTICIPANTS: Eighteen participants with SCI who underwent surgeries; completed semi-structured interviews and survey measures. INTERVENTIONS: Not applicable. OUTCOMES MEASURES: Semi-structured interviews were coded to reflect factors, DM enactment, and outcomes, including surgery satisfaction and quality of life (QOL). Quantitative measures included COMRADE, Ways of Coping Questionnaire, Bladder and Bowel Treatment Inventory, PROMIS Global Health and Cognitive Abilities scales, and SCI-QOL Bladder and Bowel short form. RESULTS: Themes identified about factors influencing DM included: recurrent symptoms and complications; balancing dissatisfaction with NBB management against surgery risks; achieving independence and life style adjustments; participant's driven solutions; support and guidance and trust in doctors; and access and barriers to DM. DM enactment varied across surgeries and individuals, revealing no clear patterns. Most participants were satisfied with the surgery outcomes. Some differences in demographics were observed between veterans and civilians. CONCLUSIONS: We have attempted to illustrate the process of NBB DM as individuals move from factors to enactment to outcomes. Attending to the complexity of the DM process through careful listening and clear communication will allow clinicians to better assist patients in making surgical decisions about NBB management.

Neurogenic Bowel and Management after Spinal Cord Injury: A Narrative Review.

People with spinal cord injury (SCI) suffer from the sequela of neurogenic bowel and its disabling complications primarily constipation, fecal incontinence, and gastrointestinal (GI) symptoms. Neurogenic bowel is a functional bowel disorder with a spectrum of defecatory disorders as well as colonic and gastrointestinal motility dysfunction. This manuscript will review the anatomy and physiology of gastrointestinal innervation, as well as the pathophysiology associated with SCI. It will provide essential information on the recent guidelines for neurogenic bowel assessment and medical management. This will allow medical providers to partner with their patients to develop an individualized bowel plan utilizing a combination of various pharmacological, mechanical and surgical interventions that prevent complications and ensure successful management and compliance. For people with SCI and neurogenic bowel dysfunction, the fundamental goal is to maintain health and well-being, promote a good quality of life and support active, fulfilled lives in their homes and communities.

Recommendations for evaluation of neurogenic bladder and bowel dysfunction after spinal cord injury and/or disease.

Objective: To provide an overview of clinical assessments and diagnostic tools, self-report measures (SRMs) and data sets used in neurogenic bladder and bowel (NBB) dysfunction and recommendations for their use with persons with spinal cord injury /disease (SCI/D).Methods: Experts in SCI/D conducted literature reviews, compiled a list of NBB related assessments and measures, reviewed their psychometric properties, discussed their use in SCI/D and issued recommendations for the National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS) Common Data Elements (CDEs) guidelines.Results: Clinical assessments included 15 objective tests and diagnostic tools for neurogenic bladder and 12 for neurogenic bowel. Following a two-phase evaluation, eight SRMs were selected for final review with the Qualiveen and Short-Form (SF) Qualiveen and the Neurogenic Bowel Dysfunction Score (NBDS) being recommended as supplemental, highly-recommended due to their strong psychometrics and extensive use in SCI/D. Two datasets and other SRM measures were recommended as supplemental.Conclusion: There is no one single measure that can be used to assess NBB dysfunction across all clinical research studies. Clinical and diagnostic tools are here recommended based on specific medical needs of the person with SCI/D. Following the CDE for SCI studies guidelines, we recommend both the SF-Qualiveen for bladder and the NBDS for bowel as relatively short measures with strong psychometrics. Other measures are also recommended. A combination of assessment tools (objective and subjective) to be used jointly across the spectrum of care seems critical to best capture changes related to NBB and develop better treatments.

Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy.

BACKGROUND: Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done. METHODS AND RESULTS: We conducted a subanalysis of 3 single-center, randomized, and blinded clinical trials: (1) TAC-HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON-DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1-year cardiac structure and function and quality-of-life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within-group, P=0.002) compared to ICM (1.5%; within-group, P=0.14; between-group, P=0.003). Similarly, stroke volume increased in DCM by 10.59 mL (P=0.046) versus ICM (-0.2 mL; P=0.73; between-group, P=0.02). End-diastolic volume improved only in ICM (10.6 mL; P=0.04) and end-systolic volume improved only in DCM (17.8 mL; P=0.049). The sphericity index decreased only in ICM (-0.04; P=0.0002). End-diastolic mass increased in ICM (23.1 g; P<0.0001) versus DCM (-4.1 g; P=0.34; between-group, P=0.007). The 6-minute walk test improved in DCM (31.1 m; P=0.009) and ICM (36.3 m; P=0.006) with no between-group difference (P=0.79). The New York Heart Association class improved in DCM (P=0.005) and ICM (P=0.02; between-group P=0.20). The Minnesota Living with Heart Failure Questionnaire improved in DCM (-19.5; P=0.002) and ICM (-6.4; P=0.03; δ between-group difference P=0.042) patients. CONCLUSIONS: Mesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac function improved preferentially in DCM patients, ICM patients experienced reverse remodeling. Mesenchymal stem cell therapy enhanced quality of life and functional capacity in both etiologies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: TAC-HFT: NCT00768066, POSEIDON: NCT01087996, POSEIDON-DCM: NCT01392625.

Positive airway pressure therapy for sleep-disordered breathing confers short-term benefits to patients with spinal cord injury despite widely ranging patterns of use.

STUDY DESIGN: Prospective, cohort study. OBJECTIVES: To evaluate the effectiveness of bi-level positive airway pressure (PAP) therapy and the patterns of use for sleep-disordered breathing (SDB) in individuals with spinal cord injury (SCI). SETTING: Academic tertiary care center, USA. METHODS: Overall, 91 adults with C1-T6 SCI for ≥3 months were recruited and 74 remained in the study to be evaluated for SDB and follow-up. Individuals with SDB but no nocturnal hypercapnia (NH) were prescribed auto-titrating PAP. Those with NH were prescribed PAP with volume-assured pressure support. Device downloads and overnight transcutaneous capnography were performed at 3, 6, and 12 months to quantify PAP use and effectiveness. Participants kept daily event logs, and quality of life (QOL) questionnaires were performed after 3, 6, and 12 months. RESULTS: Overall, 45% of 91 participants completed the study. There was great diversity among SCI patients in PAP utilization; after 3 months, 37.8% of participants used PAP for ≥70% nights and ≥240 min per night, whereas 42.2% seldom used PAP and 20% used PAP sporadically or for short periods. PAP therapy was effective in improving OSA in 89% and nocturnal hypercapnia in 77%. Higher PAP pressures predicted higher levels of device use. There were marked reductions in symptoms of autonomic dysreflexia (AD) and orthostatic hypotension as well as some improved indices of QOL. CONCLUSIONS: Despite widely diverse patterns of use, PAP therapy may have short-term benefits with regard to QOL and reducing episodes of dizziness and autonomic dysreflexia.

Simplified Approach to Diagnosing Sleep-Disordered Breathing and Nocturnal Hypercapnia in Individuals With Spinal Cord Injury.

OBJECTIVE: To evaluate a strategy of home-based testing to diagnose sleep-disordered breathing and nocturnal hypercapnia in individuals with spinal cord injury (SCI). DESIGN: Case series. SETTING: Referral center. PARTICIPANTS: Adults with C1-T6 SCI (N=81). Individuals were eligible if ≥ 18 years old, with SCI of ≥ 3 months' duration, living within 100 miles of the study site, and not meeting exclusion criteria. Of the 161 individuals recruited from the SCI Model System database who were not enrolled, reasons were not interested in participating, change of location, prior positive pressure ventilation use, or medical contraindication. Ten individuals did not complete the study. INTERVENTIONS: Performance of an unsupervised home sleep apnea test combined with transcutaneous partial pressure of carbon dioxide/oxygen saturation by pulse oximetry monitoring. MAIN OUTCOME MEASURES: Prevalence of sleep-disordered breathing and nocturnal hypercapnia. Clinical and physiological variables were examined to determine which, if any, correlate with the severity of sleep-disordered breathing. RESULTS: Obstructive sleep apnea (OSA) was found in 81.3% of individuals, central sleep apnea (CSA) was found in 23.8%, and nonspecific hypopnea events, where respiratory effort was too uncertain to classify, were present in 35%. Nonspecific hypopnea events correlated strongly with CSA but weakly with OSA, suggesting that conventional sleep apnea test scoring may underestimate central/neuromuscular hypopneas. Nocturnal hypercapnia was present in 28% and oxygen desaturation in 18.3%. Neck circumference was the primary predictor for OSA, whereas baclofen use and obstructive apnea/hypopnea index weakly predicted CSA. Awake transcutaneous partial pressure of carbon dioxide and CSA were only marginally associated with nocturnal hypercapnia. CONCLUSIONS: Unsupervised home sleep apnea testing with transcutaneous capnography effectively identifies sleep-disordered breathing and nocturnal hypercapnia in individuals with SCI.

The Severity of Bowel Dysfunction in Patients with Neurogenic Bladder.

PURPOSE: Patients with neurological conditions often experience severe debilitating lower urinary and bowel dysfunction in addition to the physical disabilities. However, only the bladder has received the attention of medical providers with neurogenic bowel being poorly understood and characterized. MATERIALS AND METHODS: This is a cross-sectional analysis of a prospective institutional neurogenic bladder database from 2010 to 2013. RESULTS: Of the 175 patients 60.6% had traumatic spinal cord injury and 18.3% had multiple sclerosis. Median ± SD FISI (Fecal Incontinence Severity Index) scores were 18.0 ± 1.39 (moderate). The median neurogenic bowel dysfunction score was 11.0 ± 0.63 (moderate). Those scores were worse in those patients with spinal cord injury and spina bifida compared to those with other diseases and in younger patients (each p = 0.020), and those in the spinal cord injury group with higher levels of injury (p = 0.0046). Based on the Bristol stool scale 65% of patients had abnormal stool consistency, mostly constipation. None of the FISI, Bristol or neurogenic bowel dysfunction scores correlated significantly with SF-12® quality of life measures. However, bladder symptom scores on M-ISI (Michigan Incontinence Symptom Index) (p = 0.05) and AUA-SI (American Urological Association symptom index) (p = 0.03) correlated with FISI severity while the neurogenic bowel dysfunction score correlated with M-ISI (ρ = 0.29, p = 0.02). Patients with abnormal stool consistency on the Bristol scale reported more urgency and stress incontinence on M-ISI. CONCLUSIONS: Bowel dysfunction is common among patients with neurogenic bladder. Those with worse bladder symptoms also experience worse bowel dysfunction. This highlights the importance of addressing both bowel and bladder dysfunction in this often poorly understood population.

Home-based overnight transcutaneous capnography/pulse oximetry for diagnosing nocturnal hypoventilation associated with neuromuscular disorders.

OBJECTIVE: To determine the utility of home-based, unsupervised transcutaneous partial pressure of carbon dioxide (tc-Pco(2)) monitoring/oxygen saturation by pulse oximetry (Spo(2)) for detecting nocturnal hypoventilation (NH) in individuals with neuromuscular disorders. DESIGN: Retrospective case series analyzed consecutively. SETTING: Multidisciplinary neuromuscular respiratory failure (NMRF) clinic at an academic institution. PARTICIPANTS: Subjects (N=35, 68.6% men; mean age, 46.9y) with spinal cord injury (45.7%) or other neuromuscular disorders underwent overnight tests with tc-Pco(2)/Spo(2) monitoring. Fifteen (42.9%) were using nocturnal ventilatory support, either bilevel positive airway pressure (BiPAP) or tracheostomy ventilation (TV). INTERVENTIONS: A respiratory therapist brought a calibrated tc-Pco(2)/Spo(2) monitor to the patient's home and provided instructions for data collection during the subject's normal sleep period. Forced vital capacity (FVC), body mass index (BMI), and exhaled end-tidal Pco(2) (ET-Pco(2)) were recorded at a clinic visit before monitoring. MAIN OUTCOME MEASURES: Detection of NH (tc-Pco(2) ≥50mmHg for ≥5% of monitoring time). Data were also analyzed to determine whether nocturnal oxygen desaturation (Spo(2) ≤88% for ≥5% of monitoring time), FVC, BMI, or daytime ET-Pco(2) could predict the presence of NH. RESULTS: NH was detected in 18 subjects (51.4%), including 53.3% of those using BiPAP or TV. NH was detected in 43.8% of ventilator-independent subjects with normal daytime ET-Pco(2) (present for 49.4%±31.5% [mean ± SD] of the study period), and in 75% of subjects with an elevated daytime ET-Pco(2) (present for 92.3%±8.7% of the study period). Oxygen desaturation, BMI, and FVC were poor predictors of NH. Only 3 attempted monitoring studies failed to produce acceptable results. CONCLUSIONS: Home-based, unsupervised monitoring with tc-Pco(2)/Spo(2) is a useful method for diagnosing NH in NMRF.

Systematic review of urological followup after spinal cord injury.

PURPOSE: There is no consensus on the appropriate urological followup of individuals after spinal cord injury but it is well known that they are at risk for renal deterioration, bladder cancer and stones. We systematically reviewed the literature to evaluate evidence of urological screening in this population. MATERIALS AND METHODS: We reviewed 385 abstracts, of which 50 met study inclusion criteria. We rated evidence using American Academy of Neurology 2004 guidelines. RESULTS: A total of 12 articles evaluated urinary tract infection screening. Patient reported symptoms used to predict urinary tract infection yielded mixed results and urine dipstick testing had the same accuracy as microscopy. Routine urine culture was unnecessary in healthy, asymptomatic individuals with normal urinalysis. Urodynamics probably must be done periodically (6 articles) but there was no information on frequency. In 11 articles ultrasound was recommended as a useful, noninvasive and possibly cost-effective screening method. Renal scan was a good method for further testing, especially if ultrasound was positive (11 articles). Evidence was sufficient (11 articles) to recommend ultrasound of the urinary tract to detect urinary tract stones with good sensitivity but not plain x-ray of the kidneys, ureters and bladder (2 articles). There was insufficient evidence to recommend urine markers or cytology for bladder cancer screening (9 articles). CONCLUSIONS: Based on this review no definitive recommendations for screening can be made except routine renal ultrasound. Urodynamics are an important part of screening but the frequency is unclear. The optimum bladder cancer screening method has not been defined.

Bladder management after spinal cord injury in the United States 1972 to 2005.

PURPOSE: Studies have shown that bladder management with an indwelling catheter for patients with spinal cord injury is associated with more urological complications such as stones, urinary infection, urethral strictures and bladder cancer. However, little is known about actual bladder management for these patients in clinical practice. MATERIALS AND METHODS: Using the National Spinal Cord Injury Database the bladder management method was determined at discharge from rehabilitation and at each 5-year followup period for 30 years. RESULTS: At discharge from rehabilitation (24,762 patients) the selection of bladder management with a condom catheter decreased steadily from a peak of 34.6% in 1972 to a low of 1.50% in 2001. The use of clean intermittent catheterization increased from 12.6% in 1972 to a peak of 56.2% in 1991. Indwelling catheter use initially decreased from 33.1% in 1972 to 16.5% in 1991 but increased to 23.1% in 2001. Of 12,984 individuals with followup data those originally using an indwelling catheter for bladder management were unlikely to switch to another method, with 71.1% continuing to use an indwelling catheter at 30 years. Individuals using clean intermittent catheterization and condom catheterization at discharge home did not continue to use these methods with only 20% and 34.6% remaining on the same management, respectively. CONCLUSIONS: With time bladder management with clean intermittent catheterization has increased in popularity. However, only 20% of patients initially on clean intermittent catheterization remained on this form of bladder management. More research on the safety of each of these methods needs to be performed to provide better guidance to aid with this decision.

Relationship of spasticity to soft tissue body composition and the metabolic profile in persons with chronic motor complete spinal cord injury.

BACKGROUND/OBJECTIVE: To determine the effects of spasticity on anthropometrics, body composition (fat mass [FM] and fat-free mass [FFM]), and metabolic profile (energy expenditure, plasma glucose, insulin concentration, and lipid panel) in individuals with motor complete spinal cord injury (SCI). METHODS: Ten individuals with chronic motor complete SCI (age, 33 +/- 7 years; BMI, 24 +/- 4 kg/m2; level of injury, C6-T11; American Spinal Injury Association A and B) underwent waist and abdominal circumferences to measure trunk adiposity. After the first visit, the participants were admitted to the general clinical research center for body composition (FFM and FM) assessment using dual energy x-ray absorptiometry. After overnight fasting, resting metabolic rate (RMR) and metabolic profile (plasma glucose, insulin, and lipid profile) were measured. Spasticity of the hip, knee, and ankle flexors and extensors was measured at 6 time points over 24 hours using the Modified Ashworth Scale. RESULTS: Knee extensor spasticity was negatively correlated to abdominal circumferences (r = -0.66, P = 0.038). After accounting for leg or total FFM, spasticity was negatively related to abdominal circumference (r = -0.67, P = 0.03). Knee extensor spasticity was associated with greater total %FFM (r = 0.64; P = 0.048), lower % FM (r = -0.66; P = 0.03), and lower FM to FFM ratio. Increased FFM (kg) was associated with higher RMR (r = 0.89; P = 0.0001). Finally, spasticity may indirectly influence glucose homeostasis and lipid profile by maintaining FFM (r = -0.5 to -0.8, P < 0.001). CONCLUSION: Significant relationships were noted between spasticity and variables of body composition and metabolic profile in persons with chronic motor complete SCI, suggesting that spasticity may play a role in the defense against deterioration in these variables years after injury. The exact mechanism is yet to be determined.