Study Objectives: Spinal cord injury (SCI) is associated with 2-5 times greater prevalence of sleep disordered breathing (SDB) than the general population. The contribution of SCI on sleep and breathing at different levels of injury using two scoring methods has not been assessed. The objectives of this study were to characterize the sleep disturbances in the SCI population and the associated physiological abnormalities using quantitative polysomnography and to determine the contribution of SCI level on the SDB mechanism. Methods: We studied 26 consecutive patients with SCI (8 females; age 42.5 ± 15.5 years; BMI 25.9 ± 4.9 kg/m 2 ; 15 cervical and 11 thoracic levels) by spirometry, a battery of questionnaires and by attended polysomnography with fl ow and pharyngeal pressure measurements. Inclusion criteria for SCI: chronic SCI (> 6 months post injury), level T6 and above and not on mechanical ventilation. Ventilation, end-tidal CO 2 (P ET CO 2 ), variability in minute ventilation (V I -CV) and upper airway resistance (R UA ) were monitored during wakefulness and NREM sleep in all subjects. Each subject completed brief history and exam, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Berlin questionnaire (BQ) and fatigue severity scale (FSS). Sleep studies were scored twice, fi rst using standard 2007 American Academy of Sleep Medicine (AASM) criteria and second using new 2012 recommended AASM criteria. Results: Mean PSQI was increased to 10.3 ± 3.7 in SCI patients and 92% had poor sleep quality. Mean ESS was increased 10.4 ± 4.4 in SCI patients and excessive daytime sleepiness (ESS ≥ 10) was present in 59% of the patients. Daytime fatigue (FSS > 20) was reported in 96% of SCI, while only 46% had high-risk score of SDB on BQ. Forced vital capacity (FVC) in SCI was reduced to 70.5% predicted in supine compared to 78.5% predicted in upright positions (p < 0.05). Likewise forced expiratory volume in fi rst second (FEV1) was 64.9% predicted in supine compared to 74.7% predicted in upright positions (p < 0.05). Mean AHI in SCI patients was 29.3 ± 25.0 vs. 20.0 ± 22.8 events/h using the new and conventional AASM scoring criteria, respectively (p < 0.001). SCI patients had SDB (AHI > 5 events/h) in 77% of the cases using the new AASM scoring criteria compared to 65% using standard conventional criteria (p < 0.05). In cervical SCI, V I decreased from 7.2 ± 1.6 to 5.5 ± 1.3 L/min, whereas P ET CO 2 and V I -CV, increased during sleep compared to thoracic SCI. Conclusion:The majority of SCI survivors have symptomatic SDB and poor sleep that may be missed if not carefully assessed. Decreased V I and increased P ET CO 2 during sleep in patients with cervical SCI relative to thoracic SCI suggests that sleep related hypoventilation may contribute to the pathogenesis SDB in patients with chronic cervical SCI. S C I E N T I F I C I N V E S T I G A T I O N SS pinal cord injury (SCI) affects a large number of adults worldwide, with an estimated incidence rate of 15 to 40 cases per million populations. The ...

Development is a dynamic process that includes an intricate balance between an increase in cell mass and an elimination of excess or defective cells. Although caspases have been intimately linked to apoptotic events, there are a few reports suggesting that these cysteine proteases can influence the differentiation and proliferation of cells. Specifically, the active form of caspase-3, which has been classified as an executor of apoptosis, recently has been implicated in a nonapoptotic role in the regulation of the cell cycle, cell proliferation, and cell differentiation. This study investigated the nonapoptotic function and phenotypic expression of active caspase-3-positive cells in the external granule cell layer (EGL) of the postnatal rat cerebellum by using biochemical and immunohistochemical analyses, respectively. Evidence that negates an apoptotic function for the caspase-3-positive EGL cells includes a failure to exhibit chromatin condensation (assessed with TOPRO), phosphatidyl serine externalization (Annexin V labeling), or DNA fragmentation (TUNEL labeling). Proliferative (Ki67-positive) and differentiated (TUJ1-positive) cells within the EGL exhibited a cytosolic expression of caspase-3, whereas terminally differentiated granule cells (NeuN-positive) in the internal granular layer and the migrating granule cells did not express active caspase-3. Thus, this study supports a nonapoptotic role for active caspase-3 in cells residing in the EGL and suggests a possible involvement in EGL proliferation and differentiation.

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