Construct validity of the international standards to document remaining autonomic function after spinal cord injury (ISAFSCI) (1st edition).

STUDY DESIGN: Observational study. OBJECTIVES: To assess the construct validity of the International Standards to Document Remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) (2012 1st Edition). SETTING: Two Canadian spinal cord injury (SCI) centers. METHODS: Data were collected between 2011-2014. Assessments included the ISAFSCI, standardized measures of autonomic function and a clinical examination. Construct validity of ISAFSCI was assessed by testing a priori hypotheses on expected ISAFSCI responses to standard measures (convergent hypotheses) and clinical variables (clinical hypotheses). RESULTS: Forty-nine participants with an average age of 45 ± 12 years were included, of which 42 (85.7%) were males, 37 (77.6%) had a neurological level of injury at or above T6, and 23 (46.9%) were assessed as having motor and sensory complete SCI. For the six General Autonomic Function component hypotheses, two hypotheses (1 clinical, 1 convergent) related to autonomic control of blood pressure and one clinical hypothesis for temperature regulation were statistically significant. In terms of the Lower Urinary Tract, Bowel and Sexual Function component of the ISAFSCI, all the hypotheses (5 convergent, 3 clinical) were statistically significant except for the hypotheses on female sexual items (2 convergent, 2 clinical), likely due to small sample size. CONCLUSION: The construct validity of ISAFSCI (2012 1st Edition) for the General Autonomic Function component was considered to be weak while it was much stronger for the Lower Urinary Tract, Bowel and Sexual Function component based on a priori hypotheses. These results can inform future psychometric studies of the ISAFSCI (2021 2nd Edition).

Inter-Rater Reliability of the International Standards to Document Remaining Autonomic Function after Spinal Cord Injury.

The autonomic nervous system can be profoundly affected after spinal cord injury (SCI). Despite its importance to quality of life, autonomic function is rarely systematically assessed in the clinical setting. The International Standards to Document Remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) is an assessment designed to determine which autonomic functions are intact, impaired, or lost after SCI. The psychometric properties of the ISAFSCI have not yet been reported. The objective of this study was to describe the inter-rater reliability of the ISAFSCI. Participants with chronic traumatic SCI (greater than 1 year) able to remain on the same medications for the study period and communicate clearly with the assessor were recruited for the study. A standard protocol minimized variation between the sites. During the first assessment, neurologic examination (ISNCSCI) was performed and ISAFSCI completed. After 10-14 days, the ISAFSCI was repeated. Inter-rater reliability was calculated using percentage agreement, kappa, and weighted kappa statistics. Participants (n = 48) had an average age of 45 ± 12 years. Forty-one (85.4%) were male, 38 (79.2%) had a SCI at or above the T6 level, 24 (50.0%) had a complete SCI. Inter-rater reliability within the general autonomic component was moderate with kappa values ranging 0.41-0.6 (p < 0.05). Within the Lower Urinary Tract, Bowel, and Sexual Function component, agreement was good-strong with weighted kappa values 0.62-0.88 (p < 0.05). Given the results, we conclude that the ISAFSCI can be considered to have at least moderate and up to strong inter-rater reliability, especially in the bladder, bowel, and sexual function component of the assessment.

Cholinergic-induced Ca2+ signaling in interstitial cells of Cajal from the guinea pig bladder.

Acetylcholine released from parasympathetic excitatory nerves activates contraction in detrusor smooth muscle. Immunohistochemical labeling of guinea pig detrusor with anti-c-Kit and anti-VAChT demonstrated a close structural relationship between interstitial cells of Cajal (ICC) and cholinergic nerves. The ability of guinea pig bladder detrusor ICC to respond to the acetylcholine analog, carbachol, was investigated in enzymatically dissociated cells, loaded with the Ca(2+) indicator fluo 4AM. ICC fired Ca(2+) transients in response to stimulation by carbachol (1/10 microM). Their pharmacology was consistent with carbachol-induced contractions in strips of detrusor which were inhibited by 4-DAMP (1 microM), an M(3) receptor antagonist, but not by the M(2) receptor antagonist methoctramine (1 microM). The source of Ca(2+) underlying the carbachol transients in isolated ICC was investigated using agents to interfere with influx or release from intracellular stores. Nifedipine (1 microM) or Ni(2+) (30-100 microM) to block Ca(2+) channels or the removal of external Ca(2+) reduced the amplitude of the carbachol transients. Application of ryanodine (30 microM) or tetracaine (100 microM) abolished the transients. The phospholipase C inhibitor, U-73122 (2.5 microM), significantly reduced the responses. 2-Aminoethoxydiethylborate (30 microM) caused a significant reduction and Xestospongin C (1 microM) was more effective, almost abolishing the responses. Intact in situ preparations of guinea pig bladder loaded with a Ca(2+) indicator showed distinctively different patterns of spontaneous Ca(2+) events in smooth muscle cells and ICC. Both cell types responded to carbachol by an increase in frequency of these events. In conclusion, guinea pig bladder detrusor ICC, both as isolated cells and within whole tissue preparations, respond to cholinergic stimulation by firing Ca(2+) transients.

Morphology and localization of interstitial cells in the guinea pig bladder: structural relationships with smooth muscle and neurons.

PURPOSE: In the current study we examined the location of interstitial cell of Cajal (ICC)-like cells in the guinea pig bladder wall and studied their structural interactions with nerves and smooth muscle cells. MATERIALS AND METHODS: Whole mount samples and cryosections of bladder tissue were labeled with primary and fluorescent secondary antibodies, and imaged using confocal and multiphoton microscopy. RESULTS: Kit positive ICC-like cells were located below the urothelium, in the lamina propria region and throughout the detrusor. In the suburothelium they had a stellate morphology and appeared to network. They made connections with nerves, as shown by double labeling experiments with anti-kit and anti-protein gene product 9.5. A network of vimentin positive cells was also found, of which many but not all were kit positive. In the detrusor kit positive cells were most often seen at the edge of smooth muscle bundles. They were elongated with lateral branches, running in parallel with the bundles and closely associated with intramural nerves. Another population of kit positive cells was seen in the detrusor between muscle bundles. These cells had a more stellate-like morphology and made connections with each other. Kit positive cells were seen tracking nerve bundles and close to intramural ganglia. Vimentin positive cells were present in the detrusor, of which some were also kit positive. CONCLUSIONS: There are several populations of ICC-like cells throughout the guinea pig bladder wall. They differ in morphology and orientation but all make connections with intramural nerves and in the detrusor they are closely associated with smooth muscle cells.