Sleep disturbance research related to a number of conditions, including ROHHAD, multiple sclerosis (MS), Marfan’s syndrome, Sjogren’s syndrome, renal failure and spinal cord injury, was presented May 18 during the ATS 2010 session “What Atypical Sleep Laboratory Patients Can Teach Us.”
Respiratory, Autonomic Disorders
The phenotypes of two disorders that are increasingly being diagnosed — congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) — were discussed in “Disorders of Respiratory and Autonomic Regulation in Childhood and Beyond: ROHHAD and CCHS.”
A growing number of children have been diagnosed with CCHS since it was first described in 1970. It has since been linked to a mutation in the PHOX2B gene, said session presenter Debra E. Weese-Mayer, M.D., who is professor of pediatrics and medical director of the Center for Autonomic Medicine in Pediatrics at Northwestern University’s Feinberg School of Medicine, and chair of the recently published ATS Statement on CCHS.
Patients with ROHHAD have a unique constellation of symptoms described in its acronym and the absence of a PHOX2B gene mutation, she said.
The diseases are “cousins” within the rubric of respiratory and autonomic disorders of infancy, childhood and adulthood (RADICA), but patients with ROHHAD typically present at an older age (1.5 to 7 years), have the herald of the rapid onset of obesity and appear to have a higher IQ than children with CCHS. The recommended clinical management includes appropriate ventilatory intervention, imaging for chest and abdominal neural crest tumors and genetic testing, and recognition of the heightened risk of sudden death in both disorders, Dr. Weese-Mayer said.
Sleep Abnormalities in MS Patients
The role of sleep apnea in contributing to fatigue in multiple sclerosis patients was addressed in “Sleepiness Versus Fatigue in Multiple Sclerosis: What Changes with CPAP?”
R. John Kimoff, M.D., FRCP, of the Respiratory Division and Sleep Disorders Centre of McGill University Health Centre in Montreal, discussed studies of fatigue that plague up to 95 percent of MS patients. The objective was to determine the relationship between sleep-disordered breathing (SDB), fatigue and sleepiness.
Researchers concluded that in MS patients, SDB is associated with fatigue, but not excessive sleepiness, he said, and the association appears to be linked to respiratory-related sleep fragmentation.
Researchers also studied the impact of obstructive sleep apnea-hypopnea treatment on fatigue in MS patients. The use of continuous positive airway pressure (CPAP) treatment was found to significantly improve fatigue scores, which were in the severe range before treatment. Scores on the Epworth Sleepiness Scale were within the normal range before treatment and changed only slightly with CPAP, Dr. Kimoff said.
Obstructive Sleep Apnea and Marfan’s Syndrome
Obstructive sleep apnea (OSA) is highly prevalent in patients with Marfan’s syndrome and sleep-disordered breathing, and may be a risk factor for aortic root dilatation and fast aneurysm expansion.
That conclusion was reported by Malcolm Kohler, M.D., of the Division of Pulmonary Medicine at University Hospital in Zurich in “Mechanical Vascular Complications of OSA Using Marfan’s Syndrome as an Example.”
Marfan’s is a systemic disorder of the connective tissue caused by an FBN1 gene mutation, and it is linked to aortic root dilatation and subsequent dissection, which are its most common life-threatening manifestations, he said.
The mechanisms underpinning the association between OSA and thoracic aortic aneurysms may be acute, and there are chronic blood pressure increases as well as large negative thoracic pressure swings, Dr. Kohler said, adding that more trials are needed to establish whether there is a causal relationship between OSA and aortic aneurysms.
Airway Dryness and OSA
Dryness can increase the surface tension of airways and the incidence of OSA, especially in post-menopausal women, according to Doug McEvoy, M.B.B.S., who presented “The Role of Sticky Airways in OSA: Evidence from Sjogren’s Syndrome.”
Studies in humans and animals have shown that a stickier liquid lining in the upper airway leads to a greater tendency to upper airway closure or apnea, said Dr. McEvoy, of the Adelaide Institute for Sleep Health and Flinders University in South Australia. The studies also showed that mouth breathing dries the airway and increases surface tension.
These findings were confirmed in “nature’s experiment,” using patients with Sjogren’s syndrome. Those with Sjogren’s have dry eyes, dry mouth, oral ulceration, dental caries, difficulty swallowing and GI and vaginal dryness. Research showed that women with Sjogren’s reported more daytime sleepiness and had more sleep-disordered breathing than women without Sjogren’s, he said.
Sleep Disturbances and the Effect of Dialysis
Patients with kidney disease commonly have sleep problems that improve with treatment, particularly dialysis, reported Mark Unruh, M.D, M.S., of the Renal-Electrolyte Division at the University of Pittsburgh Medical Center, in his presentation “OSA Pathogenesis: What Have We Learned from Renal Failure?”
Chronic kidney disease and end-stage renal disease patients are at risk for OSA, he said, and studies show that either nocturnal hemodialysis or peritoneal dialysis, which can be done during sleep, help reduce sleep apnea. In addition, some patients select daily dialysis because it improves their sleep and energy levels.
Risk factors for sleep apnea in patients with kidney disease include neuropathy and myopathy secondary to uremic toxins, altered lung volumes, upper airway edema and acid/base disturbances on the ventilatory drive.
Besides peritoneal dialysis, treatments that can help reduce sleep apnea, Dr. Unruh said, include alcohol cessation, weight loss, sleeping on the patient’s side, mandibular advancement and positive airway pressure.
Sleep Disorders in Quadriplegics
The physiologic changes occurring in quadriplegia and how these could affect sleep were discussed in “Sleep Disorders After Spinal Cord Injury” by David Berlowitz, Ph.D., of the Institute for Breathing and Sleep at Austin Health in Melbourne, Australia.
Sleep disorders predominate after a spinal injury, with symptoms such as rhythmic leg jerks and arousal, he said, adding that the melatonin pathway is disrupted in complete quadriplegia. Studies also show that OSA often develops within two to four weeks of injury.
Most quadriplegics are males who have larger abdomens and necks, reduced lung volumes, and their upper airways are more compliant and/or collapsible. The most common treatment is CPAP, which is feasible in acute quadriplegia and poorly tolerated in chronic quadriplegia, Dr. Berlowitz said.
Because CPAP is poorly tolerated in these paralyzed patients, he called for alternative treatments besides CPAP as well as studies about the effect of pathway disruptions.