Brain, breathing issues drive sleep problems in SMA: Study
Disruption tied to brain changes in addition to weak muscles
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- Sleep problems in SMA are caused by weak respiratory muscles and brain changes.
- Symptoms include fragmented sleep, fatigue, and neurocognitive/psychiatric issues.
- Treatments help, but regular sleep analysis and multidisciplinary care are crucial.
Sleep issues, common in people with spinal muscular atrophy (SMA), may be driven not only by nighttime breathing problems linked to weak respiratory muscles but also by changes in how the brain regulates sleep, a review of studies suggests.
“Sleep disturbances in SMA are multifactorial, reflecting both respiratory muscle weakness and central nervous system [brain and spinal cord] involvement,” the researchers wrote, adding that regular sleep analysis and respiratory assessments are recommended in the follow-up of all SMA patients.
The study, “Sleep phenotypes and respiratory disturbances in spinal muscular atrophy: A systematic review of clinical evidence,” was published in Sleep Medicine.
SMA is caused mainly by genetic mutations that result in a deficiency of the survival motor neuron (SMN) protein, which is essential for the health of motor neurons, the nerve cells that control movement. As these cells are lost, muscles weaken, making breathing problems a common SMA symptom.
Studies have shown that breathing difficulties during sleep, such as persistent shallow breathing (nocturnal hypoventilation) or repeated pauses in breathing (apnea), can appear before more obvious respiratory problems develop during the day. These nighttime breathing problems can disrupt normal sleep.
Researchers note need for studying sleep in SMA
Research suggests that sleep problems in SMA are not limited to breathing issues. Changes in sleep patterns also point to possible involvement of the brain in sleep impairment in SMA.
Given that “poor sleep quality is increasingly recognized as a contributor to neurocognitive impairment, fatigue, and psychiatric symptoms such as anxiety and depression,” thorough “evaluation of sleep in SMA is of increasing relevance,” the researchers wrote.
The scientists, in Italy, conducted a systematic review of studies identified through two online databases. The team also examined how noninvasive ventilation (NIV, a type of breathing support) and disease-modifying therapies affect sleep outcomes.
Across 233 studies initially identified, 20 were included in the analysis. These ranged from single-patient case reports to larger studies involving more than 100 participants, and included both children and adults with SMA types 1 to 3.
Fifteen of the included studies examined breathing disturbances during sleep. Across these studies, nocturnal hypoventilation was consistently reported in people with SMA, in some cases even without obvious low blood oxygen levels.
“These findings suggest that respiratory instability represents a key determinant of sleep disruption in SMA,” the researchers wrote, noting that this is consistent with previous studies showing high rates of breathing problems during sleep in both children and adults with the disease.
Seven studies using full polysomnography (overnight sleep testing) showed that sleep patterns are often altered in SMA. Common findings included less time spent in the deeper, more restorative stages of sleep, more time in lighter sleep, lower sleep efficiency, and, in some studies, more wake time after sleep onset. Together, these changes point to fragmented and less efficient sleep.
The researchers noted that these abnormalities “appear to be related to disease severity.”
Four studies examined sleep stability more closely using cyclic alternating pattern (CAP) analysis, a physiological measure of sleep stability. These studies found CAP changes suggesting impaired regulation of brief awakenings during sleep, meaning the brain may not properly maintain stable sleep. According to the researchers, this may reflect broader effects of SMN protein deficiency on the nervous system.
These abnormalities were detected even in patients whose standard sleep measures were only mildly altered, suggesting that CAP analysis may reveal subtle changes in brain function that routine sleep tests miss. Long-term NIV use only partly normalized these CAP changes.
Ten studies evaluating treatment effects showed that NIV consistently improved nighttime breathing, reducing breathing interruptions and improving overnight blood oxygen levels. Disease-modifying therapies Spinraza (nusinersen) and Zolgensma (onasemnogene abeparvovec-xioi) were also associated with improvements in some sleep measures, including oxygen saturation, a measure of how much oxygen is carried in the blood, and sleep efficiency.
Even so, smaller sleep-related breathing problems often persisted despite treatment, suggesting that current therapies may not fully resolve sleep disturbances in SMA.
The findings show sleep disturbances are a “critical but often underrecognized” part of the disease, the researchers wrote.
Because sleep impairment has broader clinical implications, the “routine and systematic incorporation of polysomnography into SMA clinical care is strongly recommended, not only to guide the initiation of NIV but also to monitor the broader impact of DMTs on sleep and respiratory function,” they said.
A “multidisciplinary approach” integrating sleep medicine, neurology, respiratory care, and psychological support “is essential to optimize patient outcomes” in SMA, the researchers wrote.
