Relationship Between Sleep-Disordered Breathing and Neurogenic Obesity in Adults With Spinal Cord Injury

Spinal cord injury (SCI) substantially increases the risk of neurogenic obesity, diabetes, and metabolic syndrome. Much like in the general population, a discussion of these syndromes in SCI would be incomplete without acknowledging the association of SCI with sleep-disordered breathing (SDB). This article will outline the interplay between obesity and obstructive sleep apnea (OSA), discussing the pathophysiology of obesity in OSA both for the general population and SCI population. The role of insulin resistance in SDB and SCI will also be examined. The epidemiology and pathophysiology of OSA and central sleep apnea in SCI are discussed through an examination of current evidence, followed by a review of central sleep apnea in SCI. Principles of diagnosis and management of SDB will also be discussed. Because sleep deprivation in itself can be a risk factor for developing obesity, the significance of comorbid insomnia in SCI is explored. Ultimately, a thorough sleep history, testing, and treatment are key to improving the sleep of individuals with SCI and to potentially reducing the impact of neurogenic obesity and metabolic syndrome.

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Effect of acetazolamide on susceptibility to central sleep apnea in chronic spinal cord injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.00532.2019 ◽

2020 ◽

Vol 128 (4) ◽

pp. 960-966

Author(s):

Geoffrey Ginter ◽

Abdulghani Sankari ◽

Mehdi Eshraghi ◽

Harold Obiakor ◽

Hossein Yarandi ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Risk Factor ◽

Sleep Apnea ◽

Sleep Disordered Breathing ◽

Central Sleep Apnea ◽

Central Apnea ◽

Cord Injury ◽

End Tidal ◽

Disordered Breathing

Spinal cord injury (SCI) is an established risk factor for central sleep apnea. Acetazolamide (ACZ), a carbonic anhydrase inhibitor, has been shown to decrease the frequency of central apnea by inducing mild metabolic acidosis. We hypothesized that ACZ would decrease the propensity to develop hypocapnic central apnea and decrease the apneic threshold. We randomized 16 participants with sleep-disordered breathing (8 SCI and 8 able-bodied controls) to receive ACZ (500 mg twice a day for 3 days) or placebo with a 1-wk washout before crossing over to the other drug arm. Study nights included polysomnography and determination of the hypocapnic apneic threshold and CO2 reserve using noninvasive ventilation. For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal Pco2 ([Formula: see text]) before and after. Steady-state plant gain, the response of end-tidal Pco2 to changes in ventilation, was calculated from [Formula: see text] and V̇e ratio during stable sleep. Controller gain, the response of ventilatory drive to changes in end-tidal Pco2, was defined as the ratio of change in V̇e between control and hypopnea to the ΔCO2 during stable non-rapid eye movement sleep. Treatment with ACZ for three days resulted in widening of the CO2 reserve (−4.0 ± 1.2 vs. −3.0 ± 0.7 mmHg for able-bodied, −3.4 ± 1.9 vs. −2.2 ± 2.2 mmHg for SCI, P < 0.0001), and a corresponding decrease in the hypocapnic apnea threshold (28.3 ± 5.2 vs. 37.1 ± 5.6 mmHg for able-bodied, 29.9 ± 5.4 vs. 34.8 ± 6.9 mmHg for SCI, P < 0.0001), respectively. ACZ significantly reduced plant gain when compared with placebo (4.1 ± 1.7 vs. 5.4 ± 1.8 mmHg/L min for able-bodied, 4.1 ± 2.0 vs. 5.1 ± 1.7 mmHg·L−1·min for SCI, P < 0.01). Acetazolamide decreased apnea-hypopnea index (28.8 ± 22.9 vs. 39.3 ± 24.1 events/h; P = 0.05), central apnea index (0.6 ± 1.5 vs. 6.3 ± 13.1 events/h; P = 0.05), and oxyhemoglobin desaturation index (7.5 ± 8.3 vs. 19.2 ± 15.2 events/h; P = 0.01) compared with placebo. Our results suggest that treatment with ACZ decreases susceptibility to hypocapnic central apnea due to decreased plant gain. Acetazolamide may attenuate central sleep apnea and improve nocturnal oxygen saturation, but its clinical utility requires further investigation in a larger sample of patients. NEW & NOTEWORTHY Tetraplegia is a risk factor for central sleep-disordered breathing (SDB) and is associated with narrow CO2 reserve (a marker of susceptibility to central apnea). Treatment with high-dose acetazolamide for 3 days decreased susceptibility to hypocapnic central apnea and reduced the frequency of central respiratory events during sleep. Acetazolamide may play a therapeutic role in alleviating central SDB in patients with cervical spinal cord injury, but larger clinical trials are needed.

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Sleep-disordered breathing is associated with brain vascular reactivity in spinal cord injury

Neurology ◽

10.1212/wnl.0000000000008619 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2181-e2191

Author(s):

Jordan W. Squair ◽

Amanda H.X. Lee ◽

Zoe K. Sarafis ◽

Geoff Coombs ◽

Otto Barak ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Sleep Apnea ◽

Sleep Disordered Breathing ◽

Population Level ◽

Chronic Fatigue ◽

Severity Of Injury ◽

Cord Injury ◽

Meta Analyses ◽

Disordered Breathing

ObjectiveTo determine the population-level odds of individuals with spinal cord injury (SCI) experiencing fatigue and sleep apnea, to elucidate relationships with level and severity of injury, and to examine associations with abnormal cerebrovascular responsiveness.MethodsWe used population-level data, meta-analyses, and primary physiologic assessments to provide a large-scale integrated assessment of sleep-related complications after SCI. Population-level and meta-analyses included more than 60,000 able-bodied individuals and more than 1,800 individuals with SCI. Physiologic assessments were completed on a homogenous sample of individuals with cervical SCI and matched controls. We examined the prevalence of (1) self-reported chronic fatigue, (2) clinically identified sleep apnea, and 3) cerebrovascular responsiveness to changing CO2.ResultsLogistic regression revealed a 7-fold elevated odds of chronic fatigue after SCI (odds ratio [OR] 7.9, 95% confidence interval [CI] 3.5–16.2), and that fatigue and trouble sleeping are correlated with the level and severity of injury. We further show that those with SCI experience elevated risk of clinically defined sleep-disordered breathing in more than 600 individuals with SCI (pooled OR 3.1, 95% CI 1.3–7.5). We confirmed that individuals with SCI experience a high rate of clinically defined sleep apnea using primary polysomnography assessments. We then provide evidence using syndromic analysis that sleep-disordered breathing is a factor strongly associated with impaired cerebrovascular responsiveness to CO2 in patients with SCI.ConclusionsIndividuals with SCI have an increased prevalence of sleep-disordered breathing, which may partially underpin their increased risk of stroke. There is thus a need to integrate sleep-related breathing examinations into routine care for individuals with SCI.

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Neuropsychological Function in Patients With Acute Tetraplegia and Sleep Disordered Breathing

SLEEP ◽

10.1093/sleep/zsw037 ◽

2016 ◽

Vol 40 (2) ◽

Cited By ~ 19

Author(s):

Rachel Schembri ◽

Jo Spong ◽

Marnie Graco ◽

David. J. Berlowitz ◽

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Information Processing ◽

Sleep Apnea ◽

Sleep Disordered Breathing ◽

Neuropsychological Function ◽

Neuropsychological Dysfunction ◽

Immediate Recall ◽

Cord Injury ◽

Disordered Breathing

Abstract Sleep disordered breathing is highly prevalent following spinal cord injury and likely caused by the injury. Beyond the devastating physical consequences of spinal cord injury, neuropsychological dysfunction is also common. In both the able-bodied and chronic spinal cord injury patients, sleep disordered breathing impairs many areas of neuropsychological function. However, this has not been investigated in patients with acute injury. Study objectives: To investigate the relationship between apnea severity and neuropsychological function in patients with acute-onset tetraplegia and sleep disordered breathing. Methods: Polysomnography and neuropsychological testing were performed on 104 participants (age M = 45.60, SD = 16.38; 10 female) across 11 international sites, 2 months postinjury (M = 60.70 days, SD = 39.48). Neuropsychological tests assessed attention, information processing, executive function, memory, learning, mood, and quality of life. Results: More severe sleep apnea was associated with poorer attention, information processing, and immediate recall. Deficits did not extend to memory. Higher preinjury intelligence and being younger reduced the associations with sleep disordered breathing; however, these protective factors were insufficient to counter the damage to attention, immediate recall, and information processing associated with sleep disordered breathing. Conclusions: These data suggest that new spinal cord injury may function as a model of “acute sleep apnea” and that more widespread sleep apnea–related deficits, including memory, may only be seen with longer exposure to apnea. These findings have important implications for functioning and skill acquisition during rehabilitation and, as such, highlight the importance of sleep health following tetraplegia.

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Sleep Disordered Breathing in Chronic Spinal Cord Injury

Journal of Clinical Sleep Medicine ◽

10.5664/jcsm.3362 ◽

2014 ◽

Vol 10 (01) ◽

pp. 65-72 ◽

Cited By ~ 46

Author(s):

Abdulghani Sankari ◽

Amy Bascom ◽

Sowmini Oomman ◽

M. Safwan Badr

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Sleep Disordered Breathing ◽

Chronic Spinal Cord Injury ◽

Cord Injury ◽

Disordered Breathing

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Sleep disordered breathing induced by cervical spinal cord injury and effect of adenosine A1 receptors modulation in rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00563.2019 ◽

2019 ◽

Vol 127 (6) ◽

pp. 1668-1676 ◽

Cited By ~ 1

Author(s):

Abdulghani Sankari ◽

Zeljka Minic ◽

Pershang Farshi ◽

Medea Shanidze ◽

Wafaa Mansour ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Sleep Disordered Breathing ◽

Cervical Spinal Cord ◽

Cervical Spinal Cord Injury ◽

Adenosine A1 Receptor ◽

Cord Injury ◽

Adenosine A1 ◽

A1 Receptor ◽

Disordered Breathing

Sleep-disordered breathing (SDB) is very common after spinal cord injury (SCI). The present study was designed to evaluate the therapeutic efficacy of adenosine A1 receptor blockade (8-cyclopentyl-1,3-dipropylxanthine, DPCPX) on SDB in a rodent model of SCI. We hypothesized that SCI induced via left hemisection of the second cervical segment (C2Hx) results in SDB. We further hypothesized that blockade of adenosine A1 receptors following C2Hx would reduce the severity of SDB. In the first experiment, adult male rats underwent left C2Hx or sham (laminectomy) surgery. Unrestrained whole body plethysmography (WBP) and implanted wireless electroencephalogram (EEG) were used for assessment of breathing during spontaneous sleep and for the scoring of respiratory events at the acute (~1 wk), and chronic (~6 wk) time points following C2Hx. During the second experiment, the effect of oral administration of adenosine A1 receptor antagonist (DPCPX, 3 times a day for 4 days) on SCI induced SDB was assessed. C2Hx animals exhibited a higher apnea-hypopnea index (AHI) compared with the sham group, respectively (35.5 ± 12.6 vs. 19.1 ± 2.1 events/h, P < 0.001). AHI was elevated 6 wk following C2Hx ( week 6, 32.0 ± 5.0 vs. week 1, 42.6 ± 11.8 events/h, respectively, P = 0.12). In contrast to placebo, oral administration of DPCPX significantly decreased AHI 4 days after the treatment (159.8 ± 26.7 vs. 69.5 ± 8.9%, P < 0.05). Cervical SCI is associated with the development of SDB in spontaneously breathing rats. Adenosine A1 blockade can serve as a therapeutic target for SDB induced by SCI. NEW & NOTEWORTHY The two key novel findings of our study included that 1) induced cervical spinal cord injury results in sleep-disordered breathing in adult rats, and 2) oral therapy with an adenosine A1 receptor blockade using DPCPX is sufficient to significantly reduce apnea-hypopnea index following induced cervical spinal cord injury.

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Diagnosis of Sleep Disordered Breathing in Patients With Chronic Spinal Cord Injury

Archives of Physical Medicine and Rehabilitation ◽

10.1016/j.apmr.2015.10.085 ◽

2016 ◽

Vol 97 (1) ◽

pp. 176-177 ◽

Cited By ~ 3

Author(s):

Abdulghani Sankari ◽

M. Safwan Badr

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Sleep Disordered Breathing ◽

Chronic Spinal Cord Injury ◽

Cord Injury ◽

Disordered Breathing

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Detection of Sleep-Disordered Breathing in Patients with Spinal Cord Injury Using a Smartphone

Sensors ◽

10.3390/s21217182 ◽

2021 ◽

Vol 21 (21) ◽

pp. 7182

Author(s):

Yolanda Castillo-Escario ◽

Hatice Kumru ◽

Ignasi Ferrer-Lluis ◽

Joan Vidal ◽

Raimon Jané

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Supine Position ◽

Sleep Disordered Breathing ◽

Cost Effective ◽

Apnea Hypopnea Index ◽

Accelerometer Data ◽

Increased Risk ◽

Cord Injury ◽

Disordered Breathing

Patients with spinal cord injury (SCI) have an increased risk of sleep-disordered breathing (SDB), which can lead to serious comorbidities and impact patients’ recovery and quality of life. However, sleep tests are rarely performed on SCI patients, given their multiple health needs and the cost and complexity of diagnostic equipment. The objective of this study was to use a novel smartphone system as a simple non-invasive tool to monitor SDB in SCI patients. We recorded pulse oximetry, acoustic, and accelerometer data using a smartphone during overnight tests in 19 SCI patients and 19 able-bodied controls. Then, we analyzed these signals with automatic algorithms to detect desaturation, apnea, and hypopnea events and monitor sleep position. The apnea–hypopnea index (AHI) was significantly higher in SCI patients than controls (25 ± 15 vs. 9 ± 7, p < 0.001). We found that 63% of SCI patients had moderate-to-severe SDB (AHI ≥ 15) in contrast to 21% of control subjects. Most SCI patients slept predominantly in supine position, but an increased occurrence of events in supine position was only observed for eight patients. This study highlights the problem of SDB in SCI and provides simple cost-effective sleep monitoring tools to facilitate the detection, understanding, and management of SDB in SCI patients.

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0597 Precision of Sleep-Disordered Breathing Event Classification Using Simulated Home Sleep Apnea Testing in Patients with Spinal Cord Injury, or Disease

SLEEP ◽

10.1093/sleep/zsaa056.594 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A228-A229

Author(s):

S Zeineddine ◽

A Sankari ◽

k Arvai ◽

A Salloum ◽

Y Abu Awad ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Patient Population ◽

Sleep Disordered Breathing ◽

Apnea Hypopnea Index ◽

Respiratory Events ◽

Respiratory Event ◽

Cord Injury ◽

The Mean ◽

Disordered Breathing

Abstract Introduction Sleep-disordered breathing (SDB) is highly prevalent among patients with spinal cord injury or disease (SCI/D). In-laboratory polysomnography (PSG) is difficult for these patients due to functional limitations and the physical construction of most sleep laboratories. Our objective was to evaluate the concordance between simulated HSAT and PSG in identifying SDB severity and subtypes of respiratory events in this patient population. Methods Within a larger study, 33 Veterans with SCI/D completed one night of in-laboratory PSG. Limited-channel HSAT was simulated by extracting 5 channels from PSG signals to include nasal pressure, thermistor, thoracic and abdominal belts, and oxygen saturation. Results Mean age of patients was 59.8 ± 10.9 years; 87.9% were male, and the average BMI was 28.1 ± 6.3. The mean Apnea-Hypopnea Index (AHI) from PSG was 35.5 ± 22.7. The mean Respiratory Event Index (REI) based on simulated HSAT was 22.5 ± 18.6. Thirty-one patients (93.9%) had SDB defined as AHI ≥5/hour. Simulated limited-channel HSAT accurately identified 32 out of 33 patients (96.96%). When SDB was further classified into mild (AHI 5-15 events/hr), moderate (AHI 15-30 events/hr), and severe (AHI>30/hr), simulated HSAT consistently underestimated the severity of underlying SDB. Spearman correlation between estimating AHI (PSG-HSAT) and subtypes of respiratory events was primarily accounted for by the difference in the number of hypopneas (r=0.72, -0.021 and -0.001 for hypopneas, obstructive and central apneas, respectively). Conclusion Our findings support the diagnostic utility of HSAT in SCI/D patients with SDB; however, HSAT underestimation of SDB may lead to difficulties in optimizing therapy. The misclassification of SDB severity is mainly driven by the number of hypopneas. Classification of hypopneas as obstrcutive or central may shed further light on the nature of this difference. Further research on the usability of HSAT devices in this patient population is needed. Support VA Rehabilitation Research and Development Service (RX002116; PI Badr and RX002885; PI Sankari) and NIH/NHLBI (K24HL143055; PI: Martin)

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