Breathing Disorders in MSATypes, Symptoms and Treatments
Disorders affecting breathing are common in patients with MSA and may arise from atrophy or overactivation of breathing or vocal cord muscles or a combination of the two, as well as degeneration in areas of the brain that control respiration.
In one type of breathing disorder, known as stridor, a characteristic wheezing sound occurs when inhaling. Stridor, which occurs in up to 42% of MSA patients, results from overactive vocal cord muscles that remain constricted, closing down the airway, when they should relax, such as during inhalation. In some patients, overcontraction of muscles that constrict the throat occurs along with atrophy, or underactivity of muscles that expand the throat4. Stridor can occur throughout the day and night, or, in some instances, only during sleep3. Patients affected by stridor may experience increased respiratory rate and heart rate during sleep7.
Stridor during sleep also can cause obstructive sleep apnea, a condition characterized by frequent, prolonged periods when breathing stops. Obstructive sleep apnea affects about 37% percent of MSA patients6 and episodes have been documented to occur as often as 32 times per hour4. Sleep apnea disrupts the phases of sleep, causing arousal from deep sleep and leading to poor sleep quality and associated physiological stress, such as lowered immune function and daytime fatigue. Decreased blood oxygen levels also result from sleep apnea, with one study reporting oxygen saturation dropping to as low as 86%, compared to a normal, healthy level of 95% to 100%5. Waveforms of stridor in MSA can be either rhythmic or semirhythmic in pattern. The authors of this review concluded that in MSA, stridor composed of the rhythmic component has a poorer outcome38.
Non-Pharmacological Treatment Options
For sleep apnea or nocturnal stridor, a doctor may recommend using a continuous positive air pressure (CPAP) machine. This device applies air pressure into the airways to keep them open. A pump creates the pressure, which is delivered through a hose connected to a face mask worn while sleeping. At first, some patients experience claustrophobic feelings from wearing the mask. As a result, it might take a few nights of using the CPAP to become accustomed to it. Pressure from the mask, which must be worn snugly to maintain the correct amount of air pressure, can also cause nasal congestion, sore or dry eyes, headache, or a skin rash where the mask contacts the face8. Some simple remedies can help manage irritations caused by the CPAP. “Artificial tears” eye drops can alleviate dry eyes, nasal salt sprays and room dehumidiers help reduce nasal stuffiness, and skin moisturizer or protectant patches help prevent skin sores where the mask contacts the face9.
Use of CPAP machines has been found to improve quality of sleep and increase alertness during the day in some MSA patients10. Patients who start CPAP therapy as early as possible after breathing problems arise tend to have better results and stay with the therapy over a longer-term10. Studies have shown that CPAP use can eliminate or reduce stridor and obstructive sleep apnea and improve blood oxygen levels11,4.
A form of positive airway pressure therapy known as bi-level positive air pressure, or BiPAP, also called adaptive servo-ventilation, assists breathing by not only using pressure to open the airways, but also by increasing the depth of respiration. A BiPAP machine is capable of modulating air flow to maintain the correct pressure to counteract the effect of air leaks in the mask or variations in the patient’s breathing rate and depth14. BiPAP may be useful in some patients with sleep apnea who have degeneration of sleep centers in the brain, known as central sleep apnea, in addition to or instead of airway obstruction15. In one study of MSA patients with central sleep apnea, BiPAP use eliminated stridor and improved blood oxygen levels15.
If sleep apnea is particularly severe or if stridor occurs during waking hours as well as at night, a CPAP machine may be impractical or ineffective. Instead, the doctor may recommend a surgical procedure called a tracheostomy. In this procedure, an opening is made in the trachea (windpipe) through the neck, and a tube is connected from the trachea to the outside so that air can more easily enter and exit the lungs. Some tracheostomy tubes are fitted with an inflatable cuff to provide a better seal between the tube and the opening in the neck. This prevents air or unwanted substances such as water or smoke from seeping in around the tube and increases air pressure between the lungs and the external environment, promoting better airflow and improving breathing12.
Learning to breathe through a tracheostomy tube may take a few days of practice. Speaking with a tracheostomy tube also is challenging at first, and may require special training. A tracheostomy requires proper cleaning and care, including regular suctioning to remove secretions from the lungs. Adverse events that might occur soon after tracheostomy surgery include bleeding around the opening, infection, obstruction of the tube, air entering the chest cavity (pneumothorax), and nerve damage13. A tracheostomy that remains in place permanently can cause long-term complications such as difficulty swallowing, blood vessel rupture, and formation of scar tissue13. Impaired blood supply to the trachea and formation of a fistula, or abnormal connection between trachea and esophagus (food pipe), are other risks associated with tracheostomy.
Other Surgical Options
Certain structures in the throat aside from vocal cord muscles can contribute to obstructive sleep apnea. Surgical options depend on which structures might be contributing to the problem. If tonsils are enlarged, a tonsillectomy may be in order. In another surgery, part of the soft palate and the uvula, the fold of tissue that projects down from the soft palate, are removed to create more space in the throat. The procedure, known as uvulopalatopharyngoplasty (also called UPPP or UP3), was shown in one study, to decrease episodes of disordered breathing by more than half in 60% of patients with obstructive sleep apnea16. However, the study also found that the majority of patients who have the surgery develop long-term side effects, including impaired ability to fully close the soft palate, a problem that can interfere with certain speech sounds.
A Cautionary Note
Though a rare occurrence, vocal cord muscles can become completely paralyzed, totally obstructing air flow. This constitutes a medical emergency and can happen regardless of which form of therapy the patient undergoes. In one instance, a MSA patient developed complete upper airway obstruction upon being anesthetized in preparation for microlaryngoscopy, an imaging procedure that involves passing a tube with a video camera into the throat17. To avoid respiratory failure when breathing problems arise due to vocal cord paralysis, exercise vigilance and be prepared to respond rapidly.
Pharmacologic Treatment Options
Injections of botulinum toxin can help relieve constriction of the larynx if sleep apnea is caused or worsened by dystonia of the throat muscles18. Botulinum injections may cause speaking and swallowing difficulties in the initial phases following injections. In one study, 51% of treatments resulted in moderate voice impairment and 14% of treatments caused participants to experience difficulty swallowing liquids19. These side effects lasted for 5.7% of the total time between treatments and resolved as the effects of the toxin wore off. Overall, botulinum therapy produced a 30% gain in function.
For patients who continue to experience daytime sleepiness while using CPAP therapy at night, a drug called modafinil, trade name Provigil, may help. Modafinil works by increasing dopamine levels. This drug has a stimulant effect on the brain without acting like an amphetamine21. It promotes activity of the neurotransmitter serotonin and inhibits activity of the neurotransmitter GABA21 and has been shown to improve scores on a sleepiness index by an average of 40%20. Potential side effects of modafinil include anxiety, headache, nausea, and nervousness. Modafinil may also cause back pain, dry mouth, indigestion, diarrhea, dizziness, tingling or burning sensations, and swelling22. Side effects have been reported in up to 36% of trial participants21.
Patients who experience supine hypertension (elevated blood pressure when lying down) may develop worsening sleep apnea symptoms due to fluid retention caused by this condition. A diuretic drug called spironolactone, trade name Aldactone, reduces blood pressure by lowering levels of aldosterone, an adrenal hormone that causes the kidneys to retain sodium and water. In one study, spironolactone reduced occurrences of sleep apnea by 45%22. Spironolactone is a potassium-sparing diuretic and can alter certain mineral levels. About 10% of patients who take this drug accumulate excess potassium and 12% of patients develop low sodium levels. Side effects include muscle paralysis and heart problems24. This drug may also impair kidney function, worsen Parkinson’s symptoms, and decrease testosterone levels25.
Fluctuating levels of the neurotransmitter serotonin may contribute to sleep apnea. At night, levels of serotonin, which signals throat muscles to relax, normally decline, particularly during the transition from wakefulness to sleep, increasing risk of airway constriction. Serotonin also influences breathing control centers in the brain. Serotonin-enhancing drugs, such as buspirone (Buspar), fluoxetine (Prozac), and paroxetine (Paxil) may help alleviate some symptoms of sleep apnea25. Animal studies have shown promising results with buspirone for improving irregular breathing patterns25,26. A clinical trial used a combination of the drugs fluoxetine, which activates serotonin in the brain, and ondansetron (Zofran), a drug that blocks certain serotonin receptors in the brain and peripheral nervous system that can cause anxiety and autonomic system activation. The combination therapy improved breathing during REM and non-REM sleep27, reducing episodes of apnea by 40%. However, use of serotonin-enhancing drugs may not alleviate daytime sleepiness30.
Potential side effects of buspirone include restlessness, nervousness, blurred vision, sweating, dry mouth, muscle pain, difficulty sleeping, and fatigue31. Side effects of fluoxetine and paroxetine include insomnia, rash, headache, joint and muscle pain, digestive disturbance, reduced blood clotting, and decreased libido32. Ondansetron has been associated with side effects such as confusion, dizziness, racing heart, fever, headache, difficulty breathing, and weakness37. Less commonly, ondenstron may cause urination problems, including decreased frequency, decreased volume, difficulty passing urine, and painful urination37.
Sold under the brand name Aricept, this drug decreases breakdown of the neurotransmitter acetylcholine, and has been found to decrease the number of incidences of apnea and low blood oxygen per night30. A clinical trial of donepezil found that it significantly decreased the time participants spent in a low-oxygen state, improved sleep efficiency, and decreased daytime sleepiness33. Potential side effects of donepezil include nausea, diarrhea, muscle cramps, difficulty sleeping, and fatigue34.
The stimulant drug armodafinil, trade name Nuvigil, can reduce daytime symptoms in sleep apnea patients. In one study, participants showed faster reaction time, better problem-solving and cognitive function, and fewer errors in a driving simulation test35. Potential side effects of armodafinil include breathing difficulty, chest tightness, racing heart, frequent urination, itching or burning sensations, and skin rash36.
MSA - What You Need to Know
- MSA Overview
- Types and Symptoms
- Treatment of MSA
- Prognosis and Outlook
- Differential Diagnosis
- Evaluation Methods
- Neurogenic Orthostatic Hypotension (nOH)
- Neurogenic Bladder
- MSA-P (Parkinsonian)
- MSA-C (Cerebellar Ataxia)
- Breathing Disorders
- REM Sleep Behavior Disorder
- Depression and Cognitive Impairment
- Neuroprotective Diet
- Advanced Planning
- What is the ANS
- History of MSA
- What First Responders Need to Know About MSA