|THE INTIMATE CONNECTION
|Year : 2018 | Volume
| Issue : 1 | Page : 63-73
Cross linkage between quality of sleep and neurologic conditions in age-diverse populations
Anne Marie Morse1, Sanjeev V Kothare2
1 Division of Pediatric Neurology and Sleep Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
2 Division of Pediatric Neurology, Department of Pediatrics, Cohen Children's Medical Center, New Hyde Park, NY, USA
|Date of Web Publication||28-Jan-2019|
Sanjeev V Kothare
Director, Division of Pediatric Neurology, Co-Director, Pediatric Sleep Program (Neurology), Cohen Children's Medical Center, Professor of Pediatrics & Neurology, Zucker School of Medicine, Hofstra/Northwell, 2001 Marcus Avenue, Suite W290, Lake Success, NY 11042
Source of Support: None, Conflict of Interest: None
Sleep medicine is inextricably interwoven with neurological health, be it in the young, adult, or geriatric population. Recent studies have highlighted its clinical benefit in autism, attention deficit hyperactivity disorder, traumatic brain injury, headache, epilepsy, multiple sclerosis, neuromuscular disease, stroke, and Alzheimer's disease. The tool of sleep health optimization may provide significant benefit and transform outcome and prognosis, and may also help yield a greater insight into many of these neurologic conditions.
Keywords: Autism, Alzheimer's disease, epilepsy, headache, multiple sclerosis, neuromuscular disease, sleep disorders
|How to cite this article:|
Morse AM, Kothare SV. Cross linkage between quality of sleep and neurologic conditions in age-diverse populations. Astrocyte 2018;5:63-73
|How to cite this URL:|
Morse AM, Kothare SV. Cross linkage between quality of sleep and neurologic conditions in age-diverse populations. Astrocyte [serial online] 2018 [cited 2022 Dec 4];5:63-73. Available from: http://www.astrocyte.in/text.asp?2018/5/1/63/250922
| Introduction|| |
Sleep medicine is a unique field as it represents a basic biologic process that affects everyone and has significant impact on the function of all organ systems. This characteristic allows for a novel measure of the field's success through evaluation of varying subspecialty disorders' outcome response to sleep medicine diagnostics and therapeutics. Neurologic disease is particularly liable to these interventions as sleep is primarily a neurologic process. Recent advancements made in sleep medicine are described through the significant impact it has made in common adult and pediatric neurologic diseases.
A comprehensive sleep assessment in patients with neurologic disease should be viewed as a necessary element to both the initial evaluation, as well as yearly re-evaluations. At minimum, screening questions evaluating for excessive daytime sleepiness (EDS) and changes in sleep patterns should be performed. Patients with high risk responses, such as positive history of sleep disturbance, new symptoms of EDS, or development of sleep dysfunction, should receive a comprehensive sleep evaluation.
A comprehensive sleep evaluation [Table 1] should begin with a detailed history that will provide the specialist with information to determine the patient's sleep–wake habits and patterns. Information obtained should include bedtime, time to fall asleep (sleep latency), waking time, and any additional time spent in bed that is not for sleep for both weekdays and weekends. Pathology specific questions, such as number and cause of nocturnal awakenings, presence of snoring and apneas, sleep-related hallucinations, or presence of cataplexy, will increase the yield of correctly identifying the presence of specific sleep pathology. The sleep history is complemented by the use of standardized inventories, such as the Epworth sleepiness scale, STOP-BANG sleep apnea questionnaire, Pittsburgh sleep quality index, or insomnia severity index.,,,
|Table 1: Comprehensive Sleep Assessment Tools Following Traumatic Brain Injury|
Click here to view
Investigations and objective data collection vary based on the most likely suspected sleep pathology [Figure 1]. For instance, patients with suspected insomnia may be asked to complete sleep diaries and actigraphy, whereas those suspected of sleep apnea, rapid eye movement (REM) behavior disorder, or narcolepsy will require sleep studies. It is important to consider that subjective complaints (e.g. EDS, sleep fragmentation) may not be well represented by the results of objective testing, such as polysomnography (PSG).
|Figure 1: Symptom-based Approach to Diagnostics for Sleep–wake Disorders in Neurologic Disease. Abbreviations: AHI: Apnea Hypopnea Index; MSL: Mean Sleep Latency; MSLT: Multiple Sleep Latency Test; NREM: Nonrapid Eye Movement; PLMD: Periodic Limb Movement Disorder; RLS: Restless Leg Syndrome; RBD: REM Behavior Disorder; REM: Rapid Eye Movement; LTM: Long-term Monitoring; EEG: Electroencephalogram.|
Click here to view
| Relationship between Sleep and Adult Neurologic Conditions|| |
Alzheimer's disease (AD) is the most common form of dementia in the United States. It affects one in 10 adults and is the sixth leading cause of death in America., Hallmark symptoms of AD are typically progressive deterioration of memory, language, and intellect; however, sleep–wake disturbances have become widely recognized as a common and often problematic behavioral symptom associated with AD. There is no curative therapy and treatments are only aimed at slowing the progression. Sleep has become a key component of these treatment regimens, as there is a growing body of evidence for a causal and bidirectional relationship between cognitive decline and sleep disturbance.
Advancing age is associated with a normal physiologic change in sleep, marked by decreased total number of hours of sleep with a disproportionate reduction of nonrapid eye movement (NREM) slow wave sleep (SWS). However, sleep changes found in patients with AD are more dramatic and include micro-architectural sleep alterations, nocturnal sleep fragmentation, and decrease in nocturnal sleep, daytime napping, and even inversion of their circadian rhythm. These sleep changes may preexist the other clinical symptoms of AD and are even thought to facilitate the development of AD. In fact, patients with insufficient sleep may develop cognitive symptoms of AD at an earlier age. The pathophysiology underlying this progression is yet to be fully elucidated [Figure 2], but at this time the evidence demonstrates that subjective and objective measures of poor sleep correlate with the severity of cortical amyloid-β (Ab) burden, cerebrospinal fluid (CSF) measures of Ab, and phosphorylated tau in CSF.,,,
|Figure 2: Proposed Interactions Between Sleep Disorders and Alzheimer's Disease (Adapted from Peter-Derex et al)|
Click here to view
Micro-architectural sleep alterations are significantly increased in those with mild cognitive impairment, those with AD, and even seen in high-risk older adults (i.e. carriers of the APOE4 allele) relative to cognitively normal older adults.,, The decrease in nocturnal sleep, EDS, and sleep fragmentation is multifactorial. However, primary sleep disorders can be responsible for these symptoms and are present in approximately 60% of AD patients, with obstructive sleep apnea (OSA) and insomnia being the most common.
Therapeutic intervention of sleep pathology has been shown to improve outcomes in AD. Treatment of insomnia and circadian rhythm disorders with melatonin and bright light therapy have shown mixed results, but with no significant side effects recorded. Therefore, melatonin and bright light therapy and cognitive behavioral therapy for insomnia are recommended, but more studies are needed to elucidate the benefit on cognition. On the contrary, the effectiveness of pharmacological agents, such as sedatives or hypnotics, has not been demonstrated in controlled trials with sleep-disturbed AD patients. In addition, caution should be emphasized as the side effect risks for sedating medications with elderly, cognitively impaired individuals are considerable and can be harmful, increase confusion, and impair self-care, along with risk for falls. Drug therapy should be considered only after behavioral approaches have failed and reversible medical/environmental causes have been ruled out. The most striking benefit is seen in the treatment of OSA with continuous positive airway pressure, which has demonstrated a significant reduction of subjective daytime sleepiness, as well as improvement in neuropsychological testing.,
Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by deterioration of the dopaminergic system primarily resulting in coordination and movement deficits. However, the neurodegeneration that occurs in PD affects multiple brain systems that are also important in the control of sleep and wakefulness, including dopaminergic, cholinergic, serotonergic, noradrenergic, and orexinergic pathways. The result is that sleep disturbances are a major non-motor feature of PD affecting up to 96% of patients. In fact, complaints of EDS and sleep fragmentation are common. Although the etiology of these complaints is related to the neurodegenerative changes, other contributing factors include medication side effects, sleep-related motor symptoms, depression, aging, and poor sleep hygiene. The frequency of sleep disturbances increases with disease progression; however, it can develop at any time during the course of PD. The presence of sleep disorders increases the frequency of complaints of poor sleep quality, reduced quality of life, increased depressive symptoms, poorer cognition, and worse fatigue.,
Historically, REM behavior disorder (RBD) has been the primary sleep disorder described in association with PD; however, the spectrum of sleep disturbances is much more diverse and multifactorial [Table 2]. In fact, other sleep disorders, such as OSA, restless legs syndrome (RLS), and periodic limb movement syndrome (PLMS), occur more frequently in patients with PD than in the general elderly population. The increased frequency of sleep disorders and their deleterious effects seen in PD led to the initial development and revision of the Parkinson's Disease Sleep Scale (PDSS-2) to aid in the early identification and treatment of sleep disruption in patients with PD., Although it is clear that there is increased risk and consequence of sleep disturbances in PD, studies evaluating the impact of treatment on motor and nonmotor symptoms have offered mixed results, with the exception that treatment of moderate-to-severe OSA does appear to reduce symptoms of EDS, consolidate nighttime sleep, and improve cognition.,
Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the central nervous system that affects about 2.5 million people in the world. Clinical symptoms, progression, and response to treatment can be variable; however, complaint of fatigue is more constant and present in up to 90% of patients. MS fatigue, however, is poorly characterized with no exact definition, accurate quantification, or etiology known. It is important to differentiate that fatigue and EDS are different symptoms. EDS is clearly defined as persistent sleepiness, even after adequate nighttime sleep. Fatigue, on the contrary, has been suggested to possibly be a direct result of demyelination and axonal loss or immunologic consequence versus a result of comorbidities found in MS, such as depression, medication side effects, pain, or sleep disturbance.
The interaction between MS, sleep, and fatigue is likely very complex [Figure 3]. Disease progression and fatigue may be a result of immune dysregulation and impairment of the blood brain barrier related to sleep deprivation, as sleep difficulties have been reported in up to 80% of patients with MS. Sleep disorders, such as RLS, PLMD, narcolepsy–cataplexy syndrome, RBD, insomnia, and sleep apnea, are three times more likely to occur in patients with MS versus the general population. It is not uncommon for the sleep disorder to be a symptom of a white matter lesion, such as cervical lesions causing RLS, focal hypothalamic lesions causing narcolepsy, and dorsal pontine lesions causing RBD., In the case of insomnia, there are generally multiple contributing factors including, but not limited to depression, anxiety, pain, nocturia, and medication side effects. Sleep apnea can be central or obstructive and related to inactivity due to disability, brainstem lesions affecting the respiratory centers, or medications that relax muscle tone in the pharynx. Treatment of these disorders can provide symptomatic improvement in sleepiness and fatigue, but it is yet to be determined if there is benefit in disease stability and reduced progression. In addition, studies are also needed to better determine any differences or impact based on severity of MS (i.e. relapsing remitting versus progressive forms), or types of disease-modifying agents used as treatment.
|Figure 3: Proposed Relationship Between Multiple Scelerosis, Fatigue, and Sleep.|
Click here to view
The relationship between stroke and sleep is more complex than the widely accepted understanding such that untreated OSA increases the risk for stroke. In fact, there is evidence that there may be a circadian relationship, an association with number of sleep hours, worsening of acute stroke outcomes in untreated sleep disorder patients, and even clinical benefit of sleep interventions in post-stroke recovery. Additionally, the development of post-stroke sleep pathology is becoming more frequently recognized.
It is well known that sleep disordered breathing (SDB), both directly and indirectly, increases the risk for stroke. OSA contributes to the development and progression of a metabolic syndrome through increased insulin resistance and deleterious effects on leptin and ghrelin, leading to lessened satiety and increased food-seeking behavior. Moreover, OSA can lead to cardiac dysrhythmias leading to cardio-embolic events resulting in stroke. However, the presence of SDB has also been shown to be associated with early neurologic worsening, higher blood pressures in the acute setting, negative impact on short-term and long-term neurologic recovery, increased mortality, and stroke recurrence risk.,, Total sleep time, with sleep hours of >9 or <6 h has also been found to contribute to stroke risk. Similarly, patients with insomnia have a 54% higher risk of developing stroke.
Acute stroke outcomes are improved with continuous positive airway pressure (CPAP) use. It has been demonstrated that CPAP may help reduce recurrent cardiovascular events, improve 5-year mortality, and reduce nighttime blood pressure. The effect on stroke outcomes or recurrence after treatment of other sleep pathology, such as RLS or insomnia, is less clear, but would likely be beneficial based on stroke risk associated with those conditions.
Post stroke, sleep pathology is increasingly recognized and can include multiple types of pathology. Insomnia, SDB, and EDS are common. However, based on location and severity of damage from the stroke, patients may also develop RBD, narcolepsy, and RLS., In addition, sleep pathology after stroke may also be related to other comorbidities, such as cardiac failure, anxiety, depression, or pain.
| Relationship between Sleep and Neurologic Conditions Found in Both Adults and Pediatric Age Group|| |
This broad group includes muscular dystrophies, myotonic dystrophy, congenital and metabolic myopathies, myasthenia gravis, peripheral neuropathies (Charcot Marie Tooth syndrome, familial dysautonomia), post-polio syndrome, amyotrophic lateral sclerosis (ALS).
Patients with neuromuscular disease are at high risk for developing sleep-related breathing disorders. A variety of mechanisms may contribute to this risk, including diaphragmatic, chest wall, and pharyngeal wall weakness, scoliosis, and restrictive lung disease. In addition, comorbid obesity, cerebral abnormalities, and physical deconditioning may further increase risk for OSA, but may also increase risk for other types of sleep pathology, such as restless leg syndrome, central sleep apnea, and insomnia.
An attended in-lab PSG of these patients is beneficial. For one, screening for sleep pathology may improve early identification of disease progression. The most common SDB abnormality found in neuromuscular disease is hypopneas and hypoventilation with a saw tooth pattern of desaturations during phasic REM sleep, which can serve as an early identifier of respiratory muscle involvement. Second, attended PSG can include monitoring of end-tidal or transcutaneous carbon dioxide levels, which is generally the most sensitive indicator of hypoventilation, a common problem in these patients. Third, misclassification of apnea type (i.e. calling an obstructive event a central event) is common due to the inability of weak respiratory muscles to expand the chest or abdomen against an occluded airway, which may affect management recommendations. Finally, it may reduce mortality risk by early identification and treatment of symptoms associated with sudden death. For example, vocal cord paralysis frequently seen in ALS patients is strongly associated with sudden death, but this risk is reduced with the treatment using positive airway pressure (PAP) or tracheostomy.
SDB in patients with neuromuscular disease, both adults and children, is generally treated with bilevel positive airway pressure (BiPAP), as opposed to other patients who generally receive CPAP. BiPAP allows reduced pressure during expiration, thereby reducing difficulty for weak patients to exhale. Supplemental oxygen may be needed in patients with continued desaturations despite optimal PAP. Inspiratory muscle training should be considered as an effective adjuvant. Central apnea is also treated with BiPAP, but servo-ventilator PAP, essentially a demand respirator, may be more optimal than BiPAP in patients with obstructive and central apneas. Treatment of sleep apnea has been shown to improve both quality of life and survival.,
At this time, recommendations for PSG have been limited to patients with sleep complaints; however, consideration for using yearly sleep evaluations and PSG as part of a reassessment of disease progression should be strongly considered. Sleep is an autonomically dynamic period that exploits the vulnerability found in patients with neuromuscular disease; thus PSG may reveal signs of progression before there are clinically obvious changes. In addition, future studies evaluating the impact of OSA treatment on comorbidities seen in neuromuscular diseases, such as cardiomyopathy and weight problems are still needed. There is limited data available on other sleep disorders and their relationship with neuromuscular disease, which could be an active area of research in the future.
Traumatic brain injury
Traumatic brain injury (TBI) occurs frequently in the United States, affecting at least 1.4 million adults and children annually. Sleep–wake disorders are a common consequence of traumatic TBI and occur in up to 70% of patients., Changes in sleep–wake function can vary among patients and is independent of cause or severity of TBI. The most common sleep disorders associated with TBI are insomnia (30%), sleep apnea (25%), followed by hypersomnia (11–28%), narcolepsy (4–6%), and periodic limb movement disorders of sleep (7–10%).,
Post-concussive sleep–wake disorders may be a result of the injury sustained through direct linear forces on the brain itself (coup) or as a result of acceleration–deceleration forces to the brain leading to shear injuries and axonal damage (contra-coup). Delayed injury, related to cellular and biochemical excito-toxicity or events of hypoxemia, hypotension, increased intracranial pressure, seizures, or hematomas may also contribute to sleep–wake disruption. The understanding of the underlying pathogenesis of the sleep–wake changes is developing, with proposed mechanisms including impaired signaling in neurons involved in normal sleep–wake control and circadian rhythm dysregulation. For instance, EDS has been found to occur as a result of impaired orexin (hyprocretin) production and signaling, as well as reduced cortical excitability., Circadian dysfunction may also be a result of reduced total production of melatonin.,
Standardized methods of assessment for sleep–wake disorders are essential in the management of a TBI patient [Table 1]., It is necessary to accurately identify and treat the sleep disorder as it is an important contributor to recovery in patients with TBI. Sleep dysfunction can have deleterious effects on comorbid postconcussive symptoms, causing or aggravating symptoms such as fatigue, pain, headaches, depression, anxiety, irritability, as well as cognitive and functional impairment.,,,
Management is patient specific, based on the presence of sleep pathology and comorbid postconcussive symptoms. Emerging data suggest a more expedient return to physical activity, which may be protective against the development of postconcussive features and that brain rest may actually be prohibitive to recovery. In terms of sleep, physical activity encourages maintenance of circadian rhythm, maintains regular sleep–wake schedules, and may prevent development of secondary fatigue. The correct treatment of postconcussive sleep–wake disorders can result in rapid improvement in quality of life.
An intimate relationship between sleep and epilepsy has been recognized since the days of Aristotle; however, the understanding of this relationship is now becoming better defined. Typically, the discussion of sleep and epilepsy focuses on sleep deprivation as a provoking agent for seizure and that some seizures are more likely to occur during sleep. It is now well established that sleep can affect frequency and occurrence of interictal spikes, as well as the occurrence, timing, and threshold of seizure. In addition, epilepsy can have deleterious effects on sleep architecture and negatively impact severity of sleep disorders.
Seizure occurrence during sleep has also become better defined. Seizures are more likely to occur during NREM sleep, specifically in stages N1 and N2. On the contrary, REM sleep is found to be relatively protective. However, if there is presence of interictal spikes during REM sleep, they tend to be a reliable identification for localization of seizure onset. There is also a more established appreciation on the timing of seizures in relation to the circadian rhythm [Table 3].
Patients with epilepsy are at a higher risk for sleep disorders leading to poor quality and insufficient sleep. Nocturnal seizures can result in a significant reduction of REM sleep and sleep efficiency, while it can increase time spent in N1. Treatment of seizures can also affect sleep. Anti-epileptic medications can impact sleep architecture and sleep quality  and vagus nerve stimulators have been suggested to increase risk for SDB.
The relationship between sleep and epilepsy is more of a vicious cycle when either is impaired. Poor sleep in epilepsy patients is multifactorial and is worsened by poorly controlled seizures, and poor sleep is associated with worsened quality of life, psychological function, and memory. The risk for sudden unexpected death in epilepsy (SUDEP) may be increased in these patients as well because of the instability and vulnerability during sleep. Improving sleep, specifically by treatment of OSA, has been noted to improve seizure frequency and an overall wellbeing in patients with epilepsy., Standardization for evaluation and implementation of sleep–wake disorders is needed to optimize seizure reduction, quality of life, and possibly impact SUDEP risk reduction.
The relationship between headache and sleep may be based in shared structural and neurotransmitters pathways. The development and radiation of head pain is thought to have a structural relationship with the trigeminal nucleus caudalis in the pons and midbrain and the hypothalamus. Similarly, these are key structures in sleep–wake control. The relationship is further enhanced through shared signaling of the serotonergic and dopaminergic systems, which provide control of the sleep–wake cycle and modulate head pain.,
The recognition of the relationship of headache to sleep disorders has been expanded as well. The relationship of headache to RLS, PLMD, and narcolepsy has been added to the already appreciated relationship of headache to OSA and parasomnias. Migraine and restless leg syndrome have a strong association. RLS is more likely in migraine patients than controls and migraine is highly prevalent in patients with RLS. Again, a dopaminergic basis is suspected. Narcoleptic patients frequently complain of headache with studies demonstrating a migraine prevalence 2–4 times greater in narcolepsy patients. It is suggested that the relationship between narcolepsy and migraine might be related to orexin and the overlapping role in inhibition of analgesia and narcolepsy. Cluster headaches tend to occur in REM sleep. Obesity hypoventilation leads to early morning headaches. Bruxism has been seen to occur more frequently with tension headaches.
The inclusion of a sleep assessment as a part of headache management is necessary. Sleep disturbances are now viewed as comorbid, predisposing, and even prognostic for headache development or persistence. However, longitudinal studies are still needed to better examine how headaches affect sleep and how sleep affects headaches.
| Relationship between Sleep and Neurologic Conditions in Pediatric Population|| |
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by persistent deficits beginning in early childhood of social communication and interaction, restricted and repetitive behaviors, interests, or activities, and which are not better explained by intellectual disability or global developmental delay. However, not part of the diagnostic criteria for autism, sleep difficulties are almost universally characteristic of children with ASD. The most common being sleep onset and maintenance insomnia, however, SDB, restless leg syndrome, parasomnias, and other primary sleep disorders are also common, and not uncommonly occur together in an individual child. It is generally accepted that these sleep disorder likely compound the behavioral difficulties found in ASD, but recent studies suggest that it may also impact language and social development. In addition, there is evidence that there may be a genetic predisposition for poor sleep, possibly shared neurotransmitter abnormalities underlying both ASD and sleep dysfunction and perhaps, enhanced disability related to nutritional deficiencies.
Children with ASD frequently have restricted diets due to food aversions that can result in nutritional deficiencies. This is becoming more recognized as a contributing factor to some sleep disturbances, such as iron deficiency and the development of RLS symptoms. Vitamin D and vitamin B12 supplementation have been associated with sleep improvement, but have not yet been evaluated in patients with ASD., This is a promising consideration for future studies to improve the sleep–wake cycle, particularly in ASD patients with evidenced nutritional deficiency.
GABA (γ-aminobutyric acid), serotonin, and melatonin are neurotransmitters that have been identified as abnormal in ASD and also play a significant role in normal sleep–wake function. The abnormal expression of these neurotransmitters is suggested to influence the high incidence of sleep dysfunction in ASD. Additionally, there are subsets of patients who have been identified with genetic abnormalities that also influence these neurotransmitters, including GABA-related genes on chromosome 15q, as well as regulatory regions in three genes in the melatonin pathway: acetylserotonin-O-methyltransferase, melatonin receptor 1A, and melatonin receptor 1B. Future studies further exploring underlying genetic predisposition should also include clock genes that regulate sleep phase or sleep duration. It is anticipated that an improved understanding of these genetic variations and their effects on sleep will lead to more optimal and tailored therapies in the future.
Attention Deficit Hyperactivity Disorder
Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder whose impact is not confined to the school day and, in fact, may represent a 24-h disorder., Sleep disturbances have been considered one of the most common comorbidities associated with ADHD. In fact, European and US guidelines both recommend to assess sleep during evaluation of an individual for suspected ADHD, and before initiation of pharmacotherapy., Historically, there is strong associative data demonstrating the relationship between sleep and ADHD, with evidence of reduced total sleep times, later bedtimes, and increased nocturnal awakenings in children with ADHD compared to their peers.,
Recent studies, however, suggest that the relationship is more intimate and that ADHD symptoms may be a daytime phenotype of impaired nocturnal sleep [Figure 4]. Abnormal melatonin production has been linked with evidence of an impaired circadian rhythm and abnormal sleep in some patients with ADHD., In addition, there is suggestion that the administration of methylphenidates may also impact endogenous production of melatonin. Studies evaluating exogenous administration of melatonin have had relatively consistent findings of improved sleep in patients with ADHD., Further studies are needed to evaluate melatonin supplementation's impact on ADHD symptoms.
|Figure 4: Conceptual Model of Relationship Between ADHD and Disordered Sleep (Modified From Hvolby, 2015).|
Click here to view
SDB is much more prevalent in children with ADHD than in the general pediatric population (25–30% versus 1–3%). Both surgical treatment of OSA and treatment with CPAP have demonstrated significant improvement in ADHD-like symptoms, as well as academic performance, sometimes resulting in the ability to discontinue ADHD medications.,, Large-scale, randomized, controlled studies are needed to better understand this relationship. These studies may also identify the demographic at-risk population, and improve understanding of the characteristics that make an individual vulnerable to development of ADHD symptoms, as these symptoms are not uniformly present in all children with OSA or sleep disruption.
| Conclusion|| |
Sleep disorders are common in diverse neurological disorders, but are often overlooked. It is important to appropriately screen for various sleep disorders on diagnosis of the neurologic syndrome, as well as institute timely reassessments for future development of sleep disorders with time [Figure 5]. Sleep medicine has been traditionally assessed by steps taken in the diagnosis and management of sleep–wake disorders, with the main endpoint being improvement in the sleep disorder as well as improved quality of life features. Advancements in sleep medicine have reinforced the role of appropriate identification and management of sleep disorders in providing improved insight into the pathogenesis for neurologic diseases, therapeutic intervention to manage neurologic disease, and also a potential tool to monitor progression of disease. This reinforces the need for comprehensive management with a multidisciplinary approach, to screen for and manage sleep disorders in neurologic disease. In addition, it underlines the necessity for future research to better develop and standardize the utilization of sleep evaluation and management in the care of patients with neurologic disease.
|Figure 5: Neurologic Disease and Symptoms Specific Approach to Sleep Evaluation. A Disease and Symptom Specific Algorithm to Guide Evaluation for Likely Sleep Disorders Found in Adult and Pediatric Neurologic Disease. Of Note, in All Patients a Detailed Sleep History Should Complement Use of Algorithm. Dotted Line Arrow is a Consideration for Patients if Sleep History is Suggestive. (a) Approach to Sleep Evaluations in Common Neurologic Diseases Found in Adults. (b) Approach to Sleep Evaluations in Common Neurologic Diseases Found in Adults and Children. (c) Approach to Sleep Evaluations in Common Neurologic Diseases Found in Children. Abbreviations: CRD: Circadian Rhythm Disorders; MSLT: Multiple Sleep Latency Test; PLMD: Periodic Limb Movement Disorder; PSG: Polysomnography; SDB: Sleep Disordered Breathing (Including Obstructive Sleep Apnea, Central Sleep Apnea, Hypoventilation Disorders); Sz: Seizure; TBI: Traumatic Brain Injury|
Click here to view
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shepard JW, Buysse DJ, Chesson AL, Dement WC, Goldberg R, Guilleminault C, et al
. History of the development of sleep medicine in the United States. J Clin Sleep Med 2005;1:61-82.
Johns MW. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 1992;15:376-81.
Chung F, Subramanyam R, Liao P, Sasaki E, Shapiro C, Sun Y. High STOP-Bang score indicates a high probability of obstructive sleep apnoea. Br J Anaesth 2012;108:768-75.
Carpenter JS, Andrykowski MA. Psychometric evaluation of the Pittsburgh sleep quality index. J Psychosom Res 1998;45:5-13.
Morin CM, Belleville G, Belanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep 2011;34:601-8.
Alzheimer's Association. 2015 Alzheimer's disease facts and figures. Alzheimers Dement 2015;11:332-84.
Mander BA, Winer JR, Jagust WJ, Walker MP. Sleep: a novel mechanistic pathway, biomarker, and treatment target in the pathology of Alzheimer's disease? Trends Neurosci 2016;39:552-66.
Peter-Derex L, Yammine P, Bastuji H, Croisile B. Sleep and Alzheimer's disease. Sleep medicine reviews 2015;19:29-38.
Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep-New York Then Westchester 2004;27:1255-74.
Liguori C, Romigi A, Nuccetelli M, Zannino S, Sancesario G, Martorana A, et al
. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA neurology 2014;71:1498-505.
Mander BA, Marks SM, Vogel JW, Rao V, Lu B, Saletin JM,et al
. [beta]-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat Neurosci 2015;18:1051-7.
Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, et al.
Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA neurology 2013;70:1537-43.
Sprecher KE, Bendlin BB, Racine AM, Okonkwo OC, Christian BT, Koscik RL, et al
. Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults. Neurobiol Aging 2015;36:2568-76.
Westerberg CE, Mander BA, Florczak SM, Weintraub S, Mesulam M, Zee PC, et al
. Concurrent impairments in sleep and memory in amnestic mild cognitive impairment. Journal of the International Neuropsychological Society 2012;18:490-500.
Prinz PN, Vitaliano PP, Vitiello MV, Bokan J, Raskind M, Peskind E, et al
. Sleep, EEG and mental function changes in senile dementia of the Alzheimer's type. Neurobiol Aging 1983;3:361-70.
Hita-Yanez E, Atienza M, Gil-Neciga E, L Cantero J. Disturbed Sleep Patterns in Elders with Mild Cognitive Impairment: The Role of Memory Decline and ApoE ε 4 Genotype. Current Alzheimer Research 2012;9:290-7.
McCurry SM, Reynolds CF, Ancoli-Israel S, Teri L, Vitiello MV. Treatment of sleep disturbance in Alzheimer's disease. Sleep Medicine Reviews 2000;4(6):603-628.
Ancoli-Israel S, Palmer BW, Cooke JR, Corey-Bloom J, Fiorentino L, Natarajan L, et al
. Cognitive effects of treating obstructive sleep apnea in Alzheimer's disease: a randomized controlled study. J Am Geriatr Soc 2008;56:2076-81.
Chong MS, Ayalon L, Marler M, Loredo JS, Corey-Bloom J, Palmer BW, et al
. Continuous positive airway pressure reduces subjective daytime sleepiness in patients with mild to moderate Alzheimer's disease with sleep disordered breathing. J Am Geriatr Soc 2006;54:777-81.
Prudon B, Duncan GW, Khoo TK, Yarnall AJ, Burn DJ, Anderson KN. Primary sleep disorder prevalence in patients with newly diagnosed Parkinson's disease. Movement Disorders 2014;29:259-62.
Neikrug AB, Maglione JE, Liu L, Natarajan L, Avanzino JA, Corey-Bloom J,et al
. Effects of sleep disorders on the non-motor symptoms of Parkinson disease. J clin sleep med 2013;9(11):1119-1129.
Rolinski M, Szewczyk-Krolikowski K, Tomlinson PR, Nithi K, Talbot K, Ben-Shlomo Y, et al
. REM sleep behaviour disorder is associated with worse quality of life and other non-motor features in early Parkinson's disease. J Neurol Neurosurg Psychiatry 2014;85:560-6.
Suzuki K, Miyamoto M, Miyamoto T, Hirata K. Parkinson's disease and sleep/wake disturbances. Current neurology and neuroscience reports 2015;15:1-11.
Chaudhuri KR, Pal S, DiMarco A, Whately-Smith C, Bridgman K, Mathew R, et al
. The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease. J Neurol Neurosurg Psychiatry 2002;73:629-35.
Trenkwalder C, Kohnen R, Högl B, Metta V, Sixel-Döring F, Frauscher B, et al
. Parkinson's disease sleep scale-validation of the revised version PDSS-2. Movement Disorders 2011;26:644-52.
Strober LB. Fatigue in multiple sclerosis: a look at the role of poor sleep. 2015.
He J, Hsuchou H, He Y, Kastin AJ, Wang Y, Pan W. Sleep restriction impairs blood-brain barrier function. J Neurosci 2014;34:14697-706.
Braley TJ, Chervin RD, Segal BM. Fatigue, tiredness, lack of energy, and sleepiness in multiple sclerosis patients referred for clinical polysomnography. Mult Scler Int 2012;2012:673936.
Sleep disorders in multiple sclerosis. Seminars in neurology: Copyright© 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. 2005.
Moreira N, Damasceno R, Medeiros C, De Bruin P, Teixeira C, Horta W, et al
. Restless leg syndrome, sleep quality and fatigue in multiple sclerosis patients. Brazilian Journal of Medical and Biological Research 2008;41:932-7.
Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ,et al
. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008;31:1071-8.
Yan-fang S, Yu-ping W. Sleep-disordered breathing: impact on functional outcome of ischemic stroke patients. Sleep Med 2009;10:717-9.
Iranzo A, Santamaria J, Berenguer J, Sanchez M, Chamorro A. Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction. Neurology 2002;58:911-6.
Wu MP, Lin HJ, Weng SF, Ho CH, Wang JJ, Hsu YW. Insomnia subtypes and the subsequent risks of stroke: report from a nationally representative cohort. Stroke 2014;45:1349-54.
Martínez-García MÁ, Soler-Cataluña JJ, Ejarque-Martínez L, Soriano Y, Román-Sánchez P, Illa FB, et al
. Continuous positive airway pressure treatment reduces mortality in patients with ischemic stroke and obstructive sleep apnea: a 5-year follow-up study. American journal of respiratory and critical care medicine 2009;180:36-41.
Culebras A, Moore JT. Magnetic resonance findings in REM sleep behavior disorder. Neurology 1989;39:1519-23.
Lee S, Kim J, Song I, An J, Kim Y, Lee K. Poststroke restless legs syndrome and lesion location: anatomical considerations. Movement Disorders 2009;24:77-84.
Raphaelson M, Inati SK. Treating sleep disorders in neurology practice. Neurol Clin 2012;30:1007-25.
Aboussouan LS. Sleep-disordered breathing in neuromuscular disease. American journal of respiratory and critical care medicine 2015;191:979-89.
Weinberg J, Klefbeck B, Borg J, Svanborg E. Polysomnography in chronic neuromuscular disease. Respiration 2003;70:349-54.
Gozal D, Thiriet P. Respiratory muscle training in neuromuscular disease: long-term effects on strength and load perception. Med Sci Sports Exerc 1999;31:1522-7.
Pinto A, Evangelista T, Carvalho Md, Alves M, Luis MS. Respiratory assistance with a non-invasive ventilator (Bipap) in MND/ALS patients: survival rates in a controlled trial. J Neurol Sci 1995;129:19-26.
Simonds AK. Recent advances in respiratory care for neuromuscular disease. CHEST Journal 2006;130:1879-86.
Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 2006;21:375-8.
Ouellet MC, Beaulieu-Bonneau S, Morin CM. Insomnia in patients with traumatic brain injury: frequency, characteristics, and risk factors. J Head Trauma Rehabil 2006;21:199-212.
Baumann CR, Werth E, Stocker R, Ludwig S, Bassetti CL. Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study. Brain 2007;130:1873-83.
Castriotta RJ, Murthy JN. Sleep disorders in patients with traumatic brain injury. CNS drugs 2011;25:175-85.
Mathias J, Alvaro P. Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: a meta-analysis. Sleep Med 2012;13:898-905.
Nardone R, Bergmann J, Kunz A, Caleri F, Seidl M, Tezzon F, et al
. Cortical excitability changes in patients with sleep-wake disturbances after traumatic brain injury. J Neurotrauma 2011;28:1165-71.
Shekleton JA, Parcell DL, Redman JR, Phipps-Nelson J, Ponsford JL, Rajaratnam SM. Sleep disturbance and melatonin levels following traumatic brain injury. Neurology 2010;74:1732-8.
Seifman MA, Adamides AA, Nguyen PN, Vallance SA, Cooper DJ, Kossmann T, et al
. Endogenous melatonin increases in cerebrospinal fluid of patients after severe traumatic brain injury and correlates with oxidative stress and metabolic disarray. Journal of Cerebral Blood Flow & Metabolism 2008;28:684-96.
Morse AM, Kothare SV, Sleep Disorders and Concussion. In Handbook of Clinical Neurology Elsevier 2018;158:127-34.
Ouellet M, Beaulieu-Bonneau S, Morin CM. Sleep-wake disturbances after traumatic brain injury. The Lancet Neurology 2015;14:746-57.
Chaput G, Giguère J, Chauny J, Denis R, Lavigne G. Relationship among subjective sleep complaints, headaches, and mood alterations following a mild traumatic brain injury. Sleep Med 2009;10:713-6.
Fichtenberg NL, Zafonte RD, Putnam S, Mann NR and Millard AE. Insomnia in a post-acute brain injury sample. Brain Injury 2002;16:197-206.
Sufrinko A, Pearce K, Elbin RJ, Covassin T, Johnson E, Collins M, et al
. The effect of preinjury sleep difficulties on neurocognitive impairment and symptoms after sport-related concussion. Am J Sports Med 2015;43:830-8.
Hou L, Han X, Sheng P, Tong W, Li Z, Xu D, et al
. Risk factors associated with sleep disturbance following traumatic brain injury: clinical findings and questionnaire based study. PLoS One 2013;8:e76087.
Grool AM, Aglipay M, Momoli F, Meehan WP, Freedman SB, Yeates KO, et al
. Association between early participation in physical activity following acute concussion and persistent postconcussive symptoms in children and adolescents. JAMA 2016;316:2504-14.
Barlow KM. Postconcussion syndrome: A review. J Child Neurol 2014;31:57-67.
Ng M, Pavlova M. Why are seizures rare in rapid eye movement sleep? Review of the frequency of seizures in different sleep stages. Epilepsy Res Treat 2013;2013:932790.
Mirzoev A, Bercovici E, Stewart LS, Cortez MA, Snead OC, Desrocher M. Circadian profiles of focal epileptic seizures: a need for reappraisal. Seizure 2012;21:412-6.
Touchon J, Baldy-Moulinier M, Billiard M, Besset A, Cadilhac J. Sleep organization and epilepsy. Epilepsy Res Suppl 1991;2:73-81.
Jain SV, Glauser TA. Effects of epilepsy treatments on sleep architecture and daytime sleepiness: An evidence-based review of objective sleep metrics. Epilepsia 2014;55:26-37.
Parhizgar F, Nugent K, Raj R. Obstructive sleep apnea and respiratory complications associated with vagus nerve stimulators. J Clin Sleep Med 2011;7:401-7.
Pornsriniyom D, won Kim H, Bena J, Andrews ND, Moul D, Foldvary-Schaefer N. Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea. Epilepsy & Behavior 2014;37:270-5.
Segal E, Vendrame M, Gregas M, Loddenkemper T, Kothare SV. Effect of treatment of obstructive sleep apnea on seizure outcomes in children with epilepsy. Pediatr Neurol 2012;46:359-62.
Evers S. Sleep and headache: the biological basis. Headache: The Journal of Head and Face Pain 2010;50:1246-51.
Akerman S, Goadsby P. Dopamine and migraine: biology and clinical implications. Cephalalgia 2007;27:1308-14.
Mascia A, Qqaacute, fra J, Schoenen J. Dopamine and migraine: A review of pharmacological, biochemical, neurophysiological, and therapeutic data. Cephalalgia 1998;18(4):174-182.
Schurks M, Winter A, Berger K, Kurth T. Migraine and restless legs syndrome: A systematic review. Cephalalgia 2014;34:777-94.
Dahmen N, Kasten M, Wieczorek S, Gencik M, Epplen J, Ullrich B. Increased frequency of migraine in narcoleptic patients: a confirmatory study. Cephalalgia 2003;23:14-9.
Holland P. Modulation of trigeminovascular processing: novel insights into primary headache disorders. Cephalalgia 2009;29:1-6.
Vendrame M, Kaleyias J, Valencia I, Legido A, Kothare SV. Polysomnographic findings in children with headaches. Pediatr Neurol 2008;39:6-11.
Botting N, Baraka N. Sleep behaviour relates to language skills in children with and without communication disorders. Int J Dev Disabil 2017. p. 1-6.
Dosman CF, Brian JA, Drmic IE, Senthilselvan A, Harford MM, Smith RW, et al
. Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol 2007;36:152-8.
Gominak S, Stumpf W. The world epidemic of sleep disorders is linked to vitamin D deficiency. Med Hypotheses 2012;79:132-5.
Ohta T, Ando K, Iwata T, Ozaki N, Kayukawa Y, Terashima M, et al.
Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12). Sleep 1991;14:414-8.
Levitt P, Eagleson KL, Powell EM. Regulation of neocortical interneuron development and the implications for neurodevelopmental disorders. Trends Neurosci 2004;27:400-6.
McCauley JL, Olson LM, Delahanty R, Amin T, Nurmi EL, Organ EL, et al.
A linkage disequilibrium map of the 1-Mb 15q12 GABAA receptor subunit cluster and association to autism. American Journal of Medical Genetics Part B: Neuropsychiatr Genet 2004;131:51-9.
Jonsson L, Ljunggren E, Bremer A, Pedersen C, Landén M, Thuresson K, et al
. Mutation screening of melatonin-related genes in patients with autism spectrum disorders. BMC medical genomics 2010;3:10.
Weiss MD, Craig SG, Davies G, Schibuk L, Stein M. New research on the complex interaction of sleep and ADHD. Curr Sleep Med Rep 2015;1:114-21.
Stein MA, Weiss M, Hlavaty L. ADHD treatments, sleep, and sleep problems: complex associations. Neurotherapeutics 2012;9:509-17.
Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann R, et al
. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry 2011;20:17-37.
Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee on Quality Improvement and Management, Wolraich M, Brown L, Brown RT, DuPaul G, et al.
ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 2011;128:1007-22.
Scott N, Blair PS, Emond AM, Fleming PJ, Humphreys JS, Henderson J, et al
. Sleep patterns in children with ADHD: a population-based cohort study from birth to 11 years. J Sleep Res 2013;22:121-8.
Hansen BH, Skirbekk B, Oerbeck B, Wentzel-Larsen T, Kristensen H. Associations between sleep problems and attentional and behavioral functioning in children with anxiety disorders and ADHD. Behav Sleep Med 2014;12:53-68.
Hvolby A. Associations of sleep disturbance with ADHD: implications for treatment. ADHD Attention Deficit and Hyperactivity Disorders 2015;7:1-18.
Nováková M, Paclt I, Ptáček R, Kuželová H, Hájek I, Sumová A. Salivary melatonin rhythm as a marker of the circadian system in healthy children and those with attention-deficit/hyperactivity disorder. Chronobiol Int 2011;28:630-7.
Van Veen MM, Kooij JS, Boonstra AM, Gordijn MC, Van Someren EJ. Delayed circadian rhythm in adults with attention-deficit/hyperactivity disorder and chronic sleep-onset insomnia. Biol Psychiatry 2010;67:1091-6.
Molina-Carballo A, Naranjo-Gómez A, Uberos J, Justicia-Martínez F, Ruiz-Ramos M, Cubero-Millán I, et al
. Methylphenidate effects on blood serotonin and melatonin levels may help to synchronise biological rhythms in children with ADHD. J Psychiatr Res 2013;47:377-383.
Mohammadi MR, Mostafavi SA, Keshavarz SA, Eshraghian MR, Hosseinzadeh P, Hosseinzadeh-Attar MJ, et al.
Melatonin effects in methylphenidate treated children with attention deficit hyperactivity disorder: a randomized double blind clinical trial. Spring. Iran J Psychiatry 2012;7:87-92.
Weiss MD, Wasdell MB, Bomben MM, Rea KJ, Freeman RD. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. Journal of the American Academy of Child & Adolescent Psychiatry 2006;45:512-9.
Soylu E, Soylu N, Yıldırım YS, Sakallıoğlu Ö, Polat C, Orhan İ. Psychiatric disorders and symptoms severity in patients with adenotonsillar hypertrophy before and after adenotonsillectomy. Int J Pediatr Otorhinolaryngol 2013;77:1775-81.
Beebe DW. Neurobehavioral morbidity associated with disordered breathing during sleep in children: a comprehensive review. Sleep 2006;29:1115-34.
Chervin RD, Ruzicka DL, Giordani BJ, Weatherly RA, Dillon JE, Hodges EK, et al
. Sleep-disordered breathing, behavior, and cognition in children before and after adenotonsillectomy. Pediatrics 2006;117:e769-78.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]