Sleep disorders are commonly seen after injuries to the central nervous system (CNS) and in neuro-degenerative disorders. Sleep disorders have been studied in traumatic brain injury (TBI), spinal cord injury (SCI), stroke, Parkinson’s disease, epilepsy, dementia, and other neurologic conditions. A multitude of sleep disorders have been described including disorders of sleep initiation, disorders of sleep maintenance, and disorders of excessive somnolence. Common sleep disorders, such as obstructive sleep apnea (OSA) have been described as well as less common sleep disorders such as central sleep apnea (CSA). For further classification of sleep disorders, please see the International Classification of Sleep Disorders – Third Edition1.
The etiology of sleep disorders is often complex and, in the setting of CNS injury, often multifactorial. In some cases, the CNS injury may be the primary cause of sleep dysfunction. Alternatively, secondary factors such as weight gain, depression, anxiety, pain, and medications may cause or exacerbate an underlying sleep disorder.
Epidemiology including risk factors and primary prevention
Sleep disorders associated with TBI include OSA, CSA, hypersomnia, periodic limb movement disorder, and circadian rhythm sleep disorders (CRSD).2-4 In TBI studies, sleep disorders are reported in up to 70% of the population.5-6 There is no correlation between the severity of the TBI and the type or severity of sleep disorder.7 Given the heterogeneous nature of TBI and the typically complex recovery, epidemiology about sleep disorders after TBI remains inconsistent.
The epidemiology data indicates stroke survivors are at an increased risk for OSA with an incidence of 50-70% of within the first 3 months following stroke.8-9 Additionally, risk factors for OSA, such as obesity and cardiovascular disease, are also risk factors for stroke. The mechanisms are unclear as discussed below but attributed to positional sleep apnea, stroke-related upper airway tone changes, and untreated OSA preceding the stroke (1A). CSA is less prevalent after stroke and has a greater probability of recovery over time when compared to OSA. CRSD are seen in 20-40% of patients after stroke.8-9
Central sleep apnea and other sleep disordered breathing (collectively SDB) has been reported in 25-60% of all SCI patients and up to 83% of cervical SCI patients.10
Other neurological disorders are associated with sleep disorders. Rapid eye movement behavior disorder (RBD) is common in Parkinson’s disease. Sleep dysfunction can occur in seizure disorders, especially if associated with frequent nocturnal seizures. Patients with Alzheimer disease often have CRSD.11
In TBI, abnormal central nervous system levels of orexin or hypocretin have been associated with CRSD.8
OSA is known to be related to obesity. The underlying contribution of the central nervous system in OSA is not clear; although, there is speculation that dysregulation of the autonomic nervous system is a factor. Functional neuroimaging studies of cognitive and neuropsychological impairments in patients with OSA have found the ascending reticular activating system, prefrontal cortices, anterior cingulate, hippocampus, and parietal cortices to be most frequently involved.12 Sleep-wake disorders following stroke have been associated with bilateral paramedian thalamic, mesencephalic, and brainstem infarcts, as well as large hemispheric strokes.5
In SCI, changes in breathing during sleep are associated with change in abdominal girth but not neck circumference.10
RBD has been associated with pathology of the dorsal mesopontine tegmentum. There is a decrease in presynaptic dopamine transporters in the striatum in this population. These findings support the theory that RBD may be part of a continuum of neurodegenerative diseases, such as Parkinson’s disease and Lewy body dementia.11
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
The diagnosis of sleep dysfunction may be overlooked, particularly if the clinician does not specifically address this issue. Often the patient does not mention difficulty sleeping. If not addressed, the problem may worsen over time.
For TBI and Stroke, sleep disturbances seem to improve over time.13 In a study of 161 patients with first-ever stroke or TIA who underwent portable sleep studies within 48 to 72 hours from admission and again after 3 months, the rate of SDB decreased from 71% to 62% with a significant reduction in central apneas but not obstructive apneas14. Again, the epidemiology data is small and inconsistent.
In SCI, chronological age has a greater correlation with sleep dysfunction than length of time after injury. The correlation, however, is nonlinear, with fewer sleep problems in patients aged 65 years and older.10
Sleep dysfunction in neurodegenerative diseases (Parkinson’s disease, Alzheimer dementia) may become more significant with progression of the disease.11
Specific secondary or associated conditions and complications
It is essential to identify sleep disorders after TBI and stroke, because they can adversely affect quality of life. Patients may suffer from excessive daytime somnolence, worsening of depression, and exacerbation of their cognitive impairment.13
Sleep dysfunction has been associated with worse outcomes after stroke. In patients with stroke, OSA is correlated with a lower Barthel score at 3 and 12 months, lower rate of discharge to home from inpatient rehabilitation, and higher mortality at 1 year 10
Poor sleep, especially OSA, can increase risk for hypertension, coronary artery disease, diabetes, and stroke. In a prospective study of stroke rehabilitation patients with a 10-year follow-up period, the risk of death was significantly higher among patients with OSA compared with controls but not among patients with CSA15. Another large population-based study show that SDB is associated with recurrent ischemic stroke, but not mortality 16.
Essentials of Assessment
The diagnosis of sleep dysfunction may be overlooked, particularly if the clinician does not specifically address this issue. The physician should ask for detailed information about the patient’s waking and sleeping times. Difficulty with sleep initiation versus sleep maintenance should be clarified. Observed snoring or witnessed apnea by a caregiver or family member is very important. (See citation 17 for further information).
The physician should review all medications, prescribed over-the-counter remedies, supplements, and recreational drugs and alcohol, that might impact sleep. Substances containing caffeine and theobromine should also be surveyed. Sleep hygiene patterns and any nonpharmacological measures used (herbal teas, sleep masks, earplugs) should also be discussed. The patient should be asked if he/she feels rested upon waking, is fatigued during the day, or takes naps. Morning headaches should be explored as they may be associated with OSA. Comorbid conditions such pain and mood disturbance should be identified, because these factors may contribute to insomnia.
Other symptoms that may be assessed include the acting out of dreams, vocalizations or screaming, or injurious activities at night, because these may be seen in patients with RBD or dementia. If seizures are a concern, discussion of convulsions, muscle aches upon waking, and incontinence should be included
The physical examination should include inspection of the neck and oropharynx, particularly if OSA is suspected6. Assessment of the visual system including testing for the ability to detect light and dark may be especially helpful in potential CRSD.
Fatigue is the most commonly reported symptom of sleep dysfunction. In patients who already have a neurologically-based cognitive impairment, fatigue will result in further decline in their cognitive abilities and have a major impact on their functional status. Fatigue can exacerbate almost any neurologic impairment. As a result, sleep disorders may disrupt balance and coordination, aggravate neurobehavioral symptoms (irritability, agitation) and mood disorders, and impair mobility and ability to perform self-care tasks. Fatigue can exist without sleep disorders and sleep disorders may not always present with fatigue.
Studies should include the following: complete blood count, thyroid function tests, and iron studies, particularly ferritin (if suspecting restless leg syndrome).
Magnetic resonance imaging of the brain may be helpful in ruling out progression of the neurological insult.
Supplemental assessment tools
Polysomnography is the standard assessment tool for suspected sleep disorders, to identify OSA, CSA, restless leg syndrome, and RBD as well as to examine sleep architecture and efficiency. Recent research indicates that this may be more cost-effective than previously thought when stratified properly 18.
Electroencephalography is used to evaluate for seizure activity. Nocturnal seizures can significantly disrupt sleep and lead to daytime sleepiness. Frontal lobe epilepsy can be confused with RBD.
Actigraphy: May help identify CRSD or poor sleep hygiene.
Specific validated sleep questionnaires such as the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index can be used to quantify sleep disturbance but cannot diagnose sleep disorders and have not always correlated with PSG. Recent findings, however, found STOPBANG and MAPI were effective in the diagnosis of sleep apnea when properly risk-stratified 18.
Early predictions of outcomes
There are no established predictors of outcomes for sleep disorders themselves. However, clinical resolution of sleep dysfunction is a positive predictor for improvement in daytime fatigue, cognition, and certain somatic symptoms, such as pain and headache.
Environmental factors can exacerbate a central nervous system-related sleep disorder and must be addressed as part of sleep management. As subsequently discussed, good sleep hygiene is critical and includes ensuring that the bedroom is suitable for optimal sleep. Hospital environments with frequent interruptions for vital sign checks, blinking lights and sounds can disrupt sleep.
Social role and social support system
Sleep disorders can lead to marital stress. The affected person may wake the partner, and ultimately it may lead partners to sleep in separate rooms and may create a loss of intimacy. Additionally, many patients who need continuous positive airway pressure (CPAP) avoid using it because the noise may affect their partners’ sleep.
Sleep disorders can also have a significant impact on work performance and general quality of life. These issues may be addressed by a psychologist or other therapist.
Rehabilitation Management and Treatments
Available or current treatment guidelines
Treatment of a central nervous system-related sleep disorder is based on the type of sleep disorder rather than the specific neurologic disease.
For insomnia, the initial intervention is education of the patient on appropriate sleep hygiene. If this is insufficient, pharmacologic treatment may include 6, 19:
- Melatonin and ramelteon (a synthetic melatonin agonist) especially if an element of CRSD is present 20
- Cautious use of soporific medications: zolpidem tartrate, eszopiclone, zaleplon
- Selective serotonin reuptake inhibitors, tricyclic or tetracyclic antidepressants (eg. t21), particularly if the insomnia is associated with a mood or anxiety disorder
- Conservative use of atypical antipsychotics (eg, quetiapine, ziprasidone, risperidone), which are occasionally helpful when agitation or psychosis are present.
In addition, researchers have examined the role of cognitive behavioral therapy and complementary medicine in the treatment of insomnia, but conclusive data is lacking.
In OSA, the use of CPAP is the standard for treatment. Additional measures may include oral appliances and weight loss. Uvulopalatopharyngoplasty is effective, but is associated with complications, such as velopharyngeal insufficiency. Benzodiazepines and opioids should be avoided.
In CSA, CPAP and bilevel positive airway pressure are the treatment of choice but were found to be effective in only 50% of patients with CSA in one study 5. Another option is transvenous phrenic nerve stimulation. Theophylline anhydrous and acetazolamide have been used to stimulate ventilation in small studies with mixed results. As with OSA, benzodiazepines and opioids should be avoided.
CRSD are often responsive to environmental modifications, such as light therapy and chronotherapy. Avoidance of naps, daytime physical activity, and keeping the room dark at night help control CRSD. Melatonin and soporific medications help with sleep at night and modafinil or armodafinil or other stimulants may reduce daytime fatigue.
RBD can be treated with clonazepam, melatonin, dopamine agonists, and donepezil.
Coordination of care
Schedules for nursing care and therapy may need to be adjusted to assure adequate sleep 6. Patients should be assessed for mood and anxiety disorders causing insomnia and referred to psychology as appropriate.
Patient & family education
The patient should be educated on good sleep hygiene including:
- Go to sleep and wake up at the same time every day, including weekends.
- Avoid caffeine after noon.
- Avoid alcohol and nicotine.
- Do not exercise immediately before bed; however, regular exercise is beneficial.
- If unable to sleep for more than 20 minutes, get out of bed and do something relaxing.
- The bedroom is for sleeping and intimate relationships (sex); avoid watching TV or working in bed.
- Take a hot bath/shower before bed.
It is also important to educate the patient about the medical sequelae of untreated sleep disorders, especially sleep apnea.
Measurements include the following: sleep log, actigraphy, Epworth Sleepiness Scale, and assessment of specific symptoms that may be related, such as headache frequency and depression.
Cutting Edge/ Emerging and Unique Concepts and Practice
Devices like portable respiratory recordings, actigraphy, and home polysomnography will make accurate diagnosis of sleep disorders readily available in the inpatient rehabilitation and home settings. Studies have shown that sleep disorders are underdiagnosed and/or misdiagnosed when relying on subjective reports alone. A more rapid and accurate diagnosis will lead to better treatment, which may lead to better neurologic outcomes.
A recent review looked at the role of repetitive transcranial magnetic stimulation (rTMS) in patients with sleep disorders. While its effect on sleep disorders secondary to brain injury has not yet been explored, its use for several other sleep disorders (including primary insomnia, RLS, OSAS and narcolepsy) looks promising. Low-frequency (LF) rTMS stimulating the right dorsolateral prefrontal cortex (DLPFC) or the posterior parietal cortex (PPC) was found to be effective to reduce cortical hyperexcitability and improve the sleep quality in subjects with chronic primary insomnia (PI). Furthermore, high-frequency (HF) and LF rTMS applied over the primary motor cortex or the supplementary motor cortex may have albeit transient beneficial effects in patients with restless legs syndrome (RLS). Stimulation of upper airway muscles during sleep by isolated TMS and by rTMS twitch can improve airflow dynamics in OSA without arousal 12, 22.
Gaps in the Evidence- Based Knowledge
The primary gaps are specific pathophysiology, biomarkers indicating a predilection for sleep disorders, and ultimately developing the most effective treatment for these disorders.
- American Academy of Sleep Medicine. International classification of sleep disorders, 3nd ed: Diagnostic and coding manual, American Academy of Sleep Medicine, Darien, IL 2014.
- Mathias JL, Alvaro PK. Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: A meta-analysis. Sleep Medicine. 2012; 898-905.
- Webster JB, Bell KR, Hussey JD, Natale TK, Lakshminarayan S. Sleep apnea in adults with traumatic brain injury: A preliminary investigation. Archives of Physical Medicine and Rehabilitation. 2001; 82: 316-321.
- Castriotta RJ, Murthy JN. Sleep disorders in patients with traumatic brain injury: a review. CNS Drugs. 2011;25:175-185.
- Hermann DM, Siccoli M, Bassetti CL. Sleep-wake disorders and stroke. Schweiz Arch Neurol Psychiatr. 2003;154:369-373.
- Barshikar S, Bell KR. Sleep disturbance after TBI. Current Neurological and Neurosurgical Reports. 2017; 17: 87-94.
- Clinchot DM, Bogner J, Mysiw W, et al. Defining sleep disturbance after TBI. Am J Phy Med Rehabil. 1998;77:291-295.
- Anderson K. Sleep disturbance and neurological disease. Clin Med. 2011;11:271-274.
- Johnson KG, Johnson DC. Frequency of sleep apnea in stroke and TIA patients: a meta-analysis.J Clin Sleep Med. 2010; 6:131–137.
- Berlowitz DJ, Brown DJ, Campbell DA, Pierce RJ. A longitudinal evaluation of sleep and breathing in the first year after cervical spinal cord injury. Arch Phys Med Rehabil. 2005;86:1193-1199.
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- Desseilles M, Dang-Vu TD, Shabus M, et al. Neuroimaging insights into the pathophysiology of sleep disorders. 2008;31:777-794.
- Nakase-Richardson R, Sherer M, Barnett SD, Yablon SA, Evans CC, Kretzmer T, Schwartz DJ, Modarres M. Prospective evaluation of the nature, course, and impact of acute sleep abnormality after traumatic brain injury. Achives of Physical Medicine and Rehabilitation. 2013; 94: 875-882
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- Sahlin C, Sandberg O, Gustafson Y, Bucht G, Carlberg B, Stenlund H, et al.. Obstructive sleep apnea is a risk factor for death in patients with stroke: a 10-year follow-up.Arch Intern Med. 2008; 168:297–301.
- Brown DL, et al. Sleep-disordered breathing is associated with recurrent ischemic stroke. Stroke. 2019; 50: 571-576.
- Sampathkumar H, et al. Assessment of sleep after traumatic braininjury. NeuroRehabilitation. 2018; 4 (3): 267-276.
- Nakase-Richardson R, et al. Cost-benefit analysis from the payor’s perspective for screening and diagnosing obstructive sleep apnea during inpatient rehabilitation for moderate to severe TBI. Archives of Physical Medicine and Rehabilitation. 2020: 101 (9); P1497-1508.
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- Grima NA, et al. Efficacy of melatonin for sleep disturbance following traumatic brain injury; a randomized controlled trial. BMC Medicine. 2018; 16 (8): 1-10.
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Original Version of the Topic
Michael R. Yochelson, MD, Kritis Dasgupta, MD. Sleep disorders in diseases of the central nervous system. Published 8/17/2012.
Previous Revisions(s) of the Topic
Craig DiTommaso, MD. Sleep disorders in diseases of the central nervous system. Published 4/6/2016
Craig DiTommaso, MD
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