Introduction: Prematurely occurring cardiovascular and pulmonary diseases are today the leading causes of death after spinal cord injury (SCI). Therefore, there is a need for increased knowledge of the cardiopulmonary health in persons aging with SCI. Here, the methodology and the cohort demographics of the Swedish Spinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA) are presented.

Methods: Cross-sectional cohort study in a community and tertiary hospital setting in southern Sweden. The participants were recruited population based and comprised persons aged 50 to 65 years with traumatic SCI for at least 5 years, level of injury C1-T6, American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-C. The study protocol was based on the baseline protocol of the Swedish Cardiopulmonary and Bioimage Study (SCAPIS) combined with generic and SCI-specific assessment tools. SCAPIS is a Swedish study designed to improve risk prediction and to study disease mechanisms of cardiovascular disease and chronic obstructive pulmonary disease (COPD) in a cohort of 30 000 persons of the general population. The assessments cover the structure and function of the cardiopulmonary and autonomic systems using bioimaging (computed tomography and ultrasound) and functional analyses (e.g. spirometry, diffusing capacity, impulse-oscillometry, 24-hour electrocardiogram and blood pressure registration and arterial stiffness). Biochemistry, anthropometry and metabolic factors (e.g. body composition and advanced glycation end products). Study-specific questionnaire and generic and SCI-specific assessment tools focusing on functioning and disability, autonomic dysfunction, psychological factors, sociodemographics, secondary health conditions (SHCs) and lifestyle.

Results: Of 38 potential participants, 25 persons comprised the final sample (20% women, mean age 58 years, mean time since injury 28 years). Spasticity and autonomic dysreflexia were common SHCs (76% and 68%, respectively). Current pressure ulcer was reported by 24% of the participants. Baclofen and bladder relaxant agents were the most commonly prescribed medications (44% and 32% respectively). Eight percent had sustained a cardiovascular event, and 72% were classified as high-risk of cardiovascular disease. However, only one case based on the mean systematic coronary risk evaluation (SCORE). Chronic kidney disease stage 3 occurred in 8% of the participants. Asthma was previously diagnosed in 8% and none had COPD. The occurrence of chronic cough and chronic phlegm was 8% and 12%, respectively. Only 16% reported participation in any regular leisure time physical activity.

Conclusions: SPICA is an in-depth assessment of the cardiopulmonary and autonomic systems in a selected group of persons with SCI, comprising those with the most pronounced disability and the lowest life expectancy. SPICA targets the organ systems of which the diseases responsible for a majority of the causes of death in this group occur. Forthcoming studies will focus on changes in structure and function of the cardiovascular and pulmonary systems, and compare the findings to matched controls from the general population. The results will contribute with new knowledge on the cardiopulmonary and autonomic health in middle-aged persons with chronic high-level SCI, and thereby provide new insights on how to design future research in order to improve the long-term care of persons with SCI.

Introduction: Reduced baroreflex gain consequent to spinal cord injury (SCI) could have profound implications for long term cardiovascular health. However, the literature does not provide unequivocal evidence for lesser gain after SCI. This may be due to the varied assessment methods used. The studies of Convertino and Koh employed the neck chamber technique to assess carotid cardiac vagal baroreflex gain. Vasoactive drugs were also employed by Koh and Krum to extrinsically induce systemic pressure changes. The Valsalva strain maneuver has been explored, however 60% of those with SCI are not able to perform it and do not demonstrate a phase IV bradycardic response. Numerous groups have exploited the beat-to-beat fluctuations inherent in blood pressure and heart rate to derive spontaneous baroreflex indices; however, prior work clearly shows that these indices are inconsistent with direct baroreflex gain measures in the able-bodied. Nonetheless, in those with SCI, spontaneous indices may provide adequate estimate of baroreflex gain due to disrupted sympathetic vasomotor control and a compensatory reliance on cardiac parasympathetic engagement for beat-to-beat blood pressure control. Thus, we investigated whether a spectral spontaneous baroreflex index reflects baroreflex gain assessed by the neck chamber technique in those with SCI and in able-bodied individuals.
Methods: We assessed baroreflex gain using a spectral spontaneous baroreflex index and the neck chamber technique in those with SCI (N=21; lesion level C1 – T10; within 2 years of injury) and in able-bodied individuals (N=13). The spectral spontaneous baroreflex index was assessed as the transfer function magnitude between RR-interval and systolic blood pressure magnitude in the 0.04 to 0.15 Hz range from 5 minutes of semi-supine resting data. We also obtained cardiovagal baroreflex gain during 5 trials of 4 neck chamber pressures corresponding to -15, -25, -35, and -45 mmHg. To determine if spontaneous baroreflex index is representative of baroreflex function, we calculated the correlation coefficient between the spectral spontaneous index and the cardiovagal baroreflex gain.
Results: As previously described in the literature, able-bodied individuals demonstrated no relationship between the spontaneous baroreflex index and baroreflex gain (r =0.2, p>0.1). However, in those with SCI, the spontaneous baroreflex index and baroreflex gain were highly related (r=0.86, p<0.05). However, the spontaneous baroreflex index was ~3x greater than baroreflex gain with an intercept of 3.6 ms/mmHg.
Conclusions: These results suggest that in those with SCI the spectral spontaneous baroreflex index is reflective of cardiovagal baroreflex gain. However, it must be noted that this does not allow for comparison to able-bodied in whom the index is inconsistent with gain. It is possible that in those with SCI, given the disrupted sympathetic control, the spontaneous baroreflex index reflects primarily the feed-back baroreflex mediated RR-interval response to blood pressure fluctuations. This may have profound implications for the importance of baroreflex control in moment by moment regulation of systemic pressure.

Introduction:
Neurogenic detrusor overactivity (NDO), a leading cause of autonomic dysreflexia (AD) in individuals with spinal cord injury (SCI), can be treated using muscarinic antagonists, e.g. fesoterodine. However, no studies have quantitatively assessed the capacity of fesoterodine to ameliorate AD. Thus, our aim was to investigate the efficacy of fesoterodine to improve lower urinary tract (LUT) function and ameliorate AD in individuals with SCI.

Methods:
This is a prospective, open-label phase II study to quantitatively assess the efficacy of fesoterodine to ameliorate AD during urodynamic investigation (UDI) and daily life, i.e. 24-hour ambulatory-blood-pressure-monitoring (ABPM). The University of British Columbia Research Ethics Boards and Health Canada approved this study. Individuals with chronic (1-year post injury), traumatic SCI at or above the level of spinal segment T6 suffering from AD and NDO were assessed at baseline (i.e. screening for eligibility, #1) and during treatment (i.e. between 10 to 12 weeks after start of fesoterodine, #2). Assessments included objective (i.e. UDI and 24-hour ABPM) and subjective (i.e. questionnaires) measures. For the latter, individuals reported urinary incontinence-related quality of life (UI-QoL) using the I-QoL questionnaire. As fesoterodine could potentially affect cognitive and bowel function negatively, we monitored both using the Montreal Cognitive Assessment (MoCA) Scale and Neurogenic Bowel Dysfunction (NBD) score. Wilcoxon signed-rank test was used to compare baseline with treatment (statistical significance: p≤0.05). Results are presented as median (1st-3rd quartile).

Results:
Analysis of 12 individuals, who completed the study revealed that fesoterodine can objectively improve LUT function, i.e. increased maximum cystometric capacity [205mL (144-300) vs. 475 (331-555), p=0.002] and volume at first NDO [125mL (65-178) vs. 215 (165-290), p=0.1]. Thus, fesoterodine decreased maximum detrusor pressure during bladder filling [44cmH₂O (24-56) vs. 12 (6-26), p=0.009], while NDO was eliminated in seven individuals (58%).
Fesoterodine objectively ameliorated artificially induced AD, i.e. smaller increase (Δ) in systolic blood pressure (SBP) during UDI #2 compared to baseline [40mmHg (24-44) vs. 27 (14-33), p=0.08] and ΔSBP until cystometric capacity (from the 1st UDI), i.e. [40mmHg (24-44) vs. 4.5 (0-10.5), p=0.002]. Furthermore, the severity, i.e. ΔSBP [59mmHg (48-69) vs. 36 (28-56), p=0.05] and frequency [14 (5-28) vs. 3 (2-12), p=0.004], of spontaneous AD during 24-h-ABPM were significantly reduced under treatment. Subjectively, fesoterodine improved UI-QoL, i.e. I-QoL total [68 (55-80) vs. 82 (77-90), p=0.02].
Treatment did not negatively impact cognitive [MoCA, 29 (25.8-29.2) vs. 29 (28-30), p=0.2] or bowel function [NBD total score, 9 (6-12.5) vs 8.5 (6-13.2), p=0.7].

Conclusion:
Fesoterodine ameliorates AD during UDI and daily life, while improving LUT function and UI-related QoL in individuals with chronic SCI suffering from NDO without negatively effecting bowel and cognitive function.

Introduction
Autonomic dysreflexia occurs particularly in women with spinal cord injury at the level of T6 or above, although it is known to occur above T10 (Greenspoon & Paul, 1986) and it is a direct life-threatening condition.

Methods
Available data was identified by conducting a thorough literature search of three main databases (MEDLINE, EMBASE and CINHAL) using appropriate Medical Subject Headings (MeSH) terms. Relevant articles were identified and reviewed.

Results
Autonomic dysreflexia was reported in 60% (Baker et al. and Cross et al. 1992) and 85% (Hughes et al. 1991) of pregnant women with SCI above T6.
Delayed or suboptimal management of AD can lead to maternal intracranial bleeding, death, uteroplacental vasoconstriction, foetal hypoxaemia and foetal bradycardia or heart rate irregularities due to paroxysmal hypertensive episodes. This is in contrast to pregnancy-induced hypertension, usually presenting as a gradual and sustained rise in blood pressure. Electronic foetal monitoring is advised to detect foetal distress secondary to AD (Cochrane review 2014).
Several measures could prevent labour-associated AD such as limited pelvic floor examination, avoiding speculum and prevention of bladder distension (Le Liepvre et al. 2017). Vaginal examinations and insertion of indwelling catheter need to be performed gently, with prior application of a topic anaesthetic to prevent triggering AD or spasms (Cochrane review 2014).
Patients should change position and have a skin examination every 2 hours during labour to prevent development of pressure ulcer which could cause AD (Pereira 2003).
Labour pains may not be perceived in patients with SCI above T10, which puts these patients at risk for unperceived delivery and AD. Anaesthesia during labour is suggested to all patients with spinal injury level at or above T6, mainly by means of an epidural catheter, to be maintained for 24 to 48 hours to prevent AD. Despite these precautions, Le Liepvre et al. reported AD in 15% of deliveries with SCI at or above T6.
Epidural analgesia should ideally be inserted as soon as labour is diagnosed or prior to artificial rupture of the membranes (Cochrane review 2014).
In patients with lesions below T6, it may be difficult to insert epidurals if the patient had undergone previous surgery of the lumbar or lower thoracic spine. Therefore, it is important to review the history of possible AD and previous spinal surgery, in the pre-conceptional and antepartum consultation (Sharpe et al. 2014).
Possible causes of postpartum AD include post-surgical pain, urinary bladder distension, uterine contractions and lactation (in lesions above T4).
Due to the concern of pure AD during labour, Caesarean delivery is not a recommended method of delivery, except for poor hypertension control despite maximum effort (Krassioukov et al. 2009).

Conclusion:
AD management during labour will require thorough assessment to remove the noxious stimuli, positioning, close monitoring of the blood pressure and conventional management using fast-acting antihypertension. Anaesthetists, obstetricians, midwife and nurses who will take care of these patients should be trained in autonomic dysreflexia issues. Early anticipation and preventive intervention are crucial.

Introduction: One of the main objectives in spinal cord injury (SCI) rehabilitation is the improvement in trunk control, to achieve independence in daily activities, to prevent complications, and in specific cases to walk. Also, one of the main causes of death in individuals with a SCI is the cardiovascular complications. In order to improve trunk control and cardiovascular function in these individuals, training in a kayak ergometer was evaluated.
Objective: To determine the effect of training in a kayak ergometer on trunk control, satisfaction with life, independence and cardiovascular function in individuals with SCI.
Methods: A randomized clinical trial was carried out in individuals with a sub-acute SCI with a neurologic level below C8.The subjects were randomly assigned to one of the following training groups:
Group A. Control, with conventional therapy (neuro-propiceptive facilitation) of 30 minutes, 5 days per week during 6 weeks.
Group B: Experimental, with training in kayak ergometer during 30 minutes, 5 times a week during 6 weeks.
Results: 14 patients have been trained. The clinical and demographic variables were similar in both groups at the beginning of the study. After training, subjects in group B had significant improvements in terms of cardiovascular function and trunk control in comparison with group A. We also found a tendency of major improvement in independence, and satisfaction with life in group B in comparison of group A.
METs (p=0.001): Group A: Initial: 4.01, final: 4.3
Group B: Initial 4.8, final 5.9
VO2: (p=0.034): Group A: Initial:17.2, final: 18.7
Group B: Initial 20.5, final 24.05
Trunk control test: (p=0.025): Group A: Initial:13.3, final: 17.2
Group B: Initial 15.6, final 22.25
SCIM-III: (p=0.131): Group A: Initial:46.7, final: 51.3
Group B: Initial 47.5, final 54.0
LiSat-9: (p=0.164): Group A: Initial:32, final: 36.3
Group B: Initial 37.7, final 46.3
Conclusion: Kayak ergometer seems to be a good option to improve trunk control, independence, cardiovascular function and satisfaction with life in individuals with sub-acute SCI.

Persons with chronic spinal cord injury (SCI) who are non-ambulatory are at risk for multiple medical consequences which promote stroke and coronary heart disease. Also, systemic inflammation has been widely noted in persons with SCI and is inversely correlated with mobility. Recent data indicate that even light-moderate intensity exercises such as walking reduce risks of comorbidities that promote stroke and coronary heart disease, prompting the American Heart Association to recommend walking at least 30 minutes per day. In uninjured persons, mechanisms underlying health benefits of physical activities include reducing systemic inflammation. Unfortunately, persons with SCI are often unable to perform upright overground or lower extremity exercise and/or do not have regular access to adaptive sports equipment. Powered exoskeletons for persons with SCI offer a means to provide physical activity through overground ambulation. They are being increasingly used and are well-liked by most users. Also, powered exoskeletal devices have marketing clearance by the US Food and Drug Administration (FDA) for personal use, thus having the potential to improve compliance for regular and continued use outside the clinic. It is currently unclear if, and to what extent, exoskeletal-assisted walking (EAW) leads to health benefits associated with walking in uninjured persons. To evaluate if EAW reduces systemic inflammation in persons with chronic SCI, we are leveraging an ongoing randomized, parallel group clinical trial of EAW training (36 sessions) in this population.
A pilot study of whole blood gene expression of 7 adult participants (N=4 males) before and after EAW has been performed. Participant injury levels were: rostral to T6 (N= 4) and caudal to T7 (N=3). RNA was extracted, RNA Sequencing (RNASeq) libraries were created with KAPA RNA HyperPrep Kits (Roche), and 100 base pair paired-end reads were collected on the NextSeq Illumina platform. Using Partek Flow software (Partek Inc., St. Louis, MO), high quality trimmed reads were aligned using STAR to the hg38genome assembly. Principal component analysis (PCA) and gene set enrichment analysis were performed to identify differentially expressed (DE) genes. By PCA, samples from able-bodied persons clustered distinctly away from chronic SCI samples, and Toll-like receptor (TLR) signaling genes were differentially expressed in chronic SCI before EAW, as we had shown previously in independent cohorts (Herman et al J Neurotrauma 2018). After EAW, the number of differentially expressed genes among participants with SCI varied widely (149 to 5,924). There were 153 up- and 20 down-regulated differentially expressed genes after EAW that were common in all SCI participants; genes and pathways related to T and B cell signaling were upregulated. There were 6,211 differentially expressed genes in any SCI participant; genes and pathways related to VEGF-, HIF1-, neurotrophin- related signaling were significantly enriched. Additional analysis of more participants is needed in order to evaluate the consistency of these findings.