Module 2 - REM Parasomnias Flashcards
What is REM Sleep Behavior Disorder (RBD) and how is it characterized?
RBD is a parasomnia characterized by the loss of normal REM sleep atonia, which permits the physical enactment of dreams. This manifests as abnormal motor behaviors—such as talking, shouting, punching, or kicking—during REM sleep. Definitive diagnosis requires both a clinical history of dream enactment behavior (DEB) and polysomnography (PSG) evidence of REM sleep without atonia (RSWA).
What is the typical demographic profile for RBD?
RBD most commonly occurs in middle-aged to older adults, with symptom onset typically between 45 and 63 years and diagnosis most frequently in the 50s or 60s. There is a strong male predominance (about 79% overall), though this is less pronounced in patients under 50.
What are the common clinical manifestations of RBD?
Clinical manifestations include a spectrum of behaviors during REM sleep: vocalizations (e.g., shouting, screaming, swearing), abrupt limb movements (e.g., flailing, kicking, punching), and complex behaviors (e.g., attempting to leave the bed). These can lead to injuries for the patient and their bed partner. Dream content is often aggressive or defensive, though daytime aggression is not typically increased.
How is RBD associated with neurodegenerative disorders?
RBD is strongly linked with synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy.
Idiopathic RBD (iRBD) often serves as a prodromal marker, with studies showing conversion rates as high as 73.5% over 12 years to one of these neurodegenerative diseases.
What biomarkers and prodromal features are commonly seen in idiopathic RBD?
Early indicators in iRBD patients include reduced olfactory function, impaired color vision, autonomic dysfunction, and subtle motor or cognitive deficits.
Imaging studies (e.g., SPECT, MRI, PET) often reveal abnormalities in brain regions controlling motor functions and REM sleep, such as reduced signal intensity in the subcoeruleus/locus coeruleus region.
What is REM sleep without atonia (RSWA) and how is it detected?
RSWA refers to the loss of the normal muscle paralysis during REM sleep, resulting in increased electromyographic (EMG) activity. It is detected via PSG using EMG leads on the chin, arms, and legs and is quantified by assessing both phasic (transient) bursts and tonic (sustained) muscle activity during REM sleep.
What screening tools and diagnostic methods are used for RBD?
Screening tools include the Mayo Sleep Questionnaire, RBD Single-Question Screen, RBD Screening Questionnaire, and RBD Questionnaire–Hong Kong. However, definitive diagnosis requires video PSG to document RSWA along with a clinical history of dream enactment behavior.
How do clinicians differentiate RBD from other sleep disorders?
Differential diagnosis involves distinguishing RBD from nightmares, recurrent isolated sleep paralysis, NREM parasomnias, nocturnal epilepsy, obstructive sleep apnea (OSA) with pseudo-RBD, and psychiatric conditions such as PTSD. Key distinguishing factors include the presence of RSWA on PSG and the nature of the dream enactment behaviors.
What neural circuitry is responsible for REM sleep atonia, and how does its dysfunction lead to RBD?
The lateral pontine tegmentum (including the subcoeruleus nucleus) and the ventromedial medulla generate REM sleep atonia via inhibitory neurotransmitters (GABA and glycine). Disruption of these circuits—due to lesions, neurodegenerative changes, or medication effects—results in RSWA and the consequent motor behaviors seen in RBD.
How does the Braak staging model relate to RBD?
The Braak staging model describes the progressive spread of α-synuclein pathology in Parkinson’s disease. Early involvement of lower brainstem structures, which control REM atonia, explains why RBD can precede overt parkinsonism by several years, serving as an early marker of synucleinopathy.
What are the primary management strategies for RBD?
Management includes environmental safety measures (e.g., removing sharp objects, using bed rails, padding furniture, employing bed alarms) to prevent injury during episodes, and pharmacologic treatments—primarily melatonin and clonazepam—to reduce the frequency and severity of dream enactment behaviors. Ongoing monitoring for neurodegenerative progression is also essential.
What are the typical dosing and side effects of clonazepam and melatonin in treating RBD?
Clonazepam is usually dosed between 0.25 and 2.0 mg at bedtime and is effective in reducing dream enactment behaviors, but may cause sedation, cognitive slowing, dizziness, and can worsen sleep apnea. Melatonin is often started at 3 mg and increased up to around 15 mg (median about 6 mg), and it has fewer side effects—mainly daytime sleepiness and occasional headaches—while possibly helping to restore REM atonia.
What distinguishes idiopathic RBD from secondary RBD?
Idiopathic RBD occurs in the absence of other identifiable causes and is often a prodromal marker for neurodegenerative diseases. Secondary RBD, by contrast, is associated with other conditions such as narcolepsy, medication use (e.g., antidepressants), alcohol withdrawal, or underlying neurological disorders.
How do REM-related parasomnias differ from each other (RBD, recurrent isolated sleep paralysis, and nightmare disorder)?
RBD is characterized by dream enactment behaviors due to RSWA.
Recurrent isolated sleep paralysis involves a temporary inability to move at sleep onset or upon awakening, often with hallucinations but without overt dream enactment.
Nightmare disorder involves distressing, well-remembered dreams with minimal motor activity and is typically associated with emotional distress upon awakening.
What PSG scoring criteria are used to diagnose RBD?
PSG criteria for RBD include detecting increased EMG activity during REM sleep. Tonic activity is defined as sustained muscle activity lasting more than 15 seconds in a 30-second epoch, while phasic activity is defined as brief bursts (0.1–5.0 seconds) in mini-epochs (typically 3-second segments) that exceed a specified threshold (often four times the background EMG). Specific percentage cut-offs (e.g., >6.5% tonic, >9.5% phasic) may be used to confirm the diagnosis.
What factors can trigger or worsen RBD symptoms?
Factors include the use of certain medications (especially antidepressants like SSRIs and tricyclics), alcohol use, sleep deprivation, and irregular sleep–wake schedules. In some cases, drug withdrawal can also precipitate RBD.
How should RBD be managed in patients with coexisting obstructive sleep apnea (OSA)?
While treating OSA (e.g., with CPAP) may improve overall sleep quality, it does not necessarily reduce RSWA. Safety measures remain crucial, and careful monitoring is needed as some RBD treatments (like clonazepam) can worsen OSA.
What is the role of environmental modifications in the management of RBD?
Environmental modifications aim to minimize injury risk during episodes by removing or padding hazardous objects, using bed rails or cushions, and sometimes employing bed alarms to alert caregivers or the patient if an episode begins.
Why is early detection of RBD important in the context of neurodegenerative disease management?
Early detection of RBD, particularly idiopathic RBD, can serve as a prodromal marker for synucleinopathies, allowing for closer monitoring and the potential early initiation of neuroprotective therapies aimed at delaying or preventing the progression of diseases such as Parkinson’s disease.
What additional treatments have been explored for RBD beyond clonazepam and melatonin?
Other treatments include dopaminergic agents (e.g., pramipexole), zonisamide, donepezil, agomelatine, and herbal supplements such as Yi-Gan San. These options are based on limited evidence and require further research to establish efficacy and safety.
How does RBD presentation differ between children and adults?
RBD is rare in children and is usually associated with conditions like narcolepsy or neurodevelopmental disorders, rather than occurring idiopathically. In adults, idiopathic RBD is more common and is strongly linked with neurodegenerative diseases.
What does “dream enactment behavior” (DEB) refer to, and why is it important for diagnosing RBD?
DEB refers to the physical movements, vocalizations, and behaviors that occur during REM sleep as a result of the loss of atonia. It is a critical clinical feature used, in combination with PSG findings of RSWA, to diagnose RBD. However, DEB alone does not confirm RBD without PSG confirmation.
What is the significance of finding RSWA without overt DEB?
RSWA without DEB indicates increased EMG activity during REM sleep on PSG in the absence of observable dream enactment. This may represent a subclinical or prodromal stage of RBD, warranting monitoring for potential future development of full RBD and neurodegenerative disease.
Why is video monitoring essential during PSG for diagnosing RBD?
Video monitoring is essential because it allows clinicians to correlate EMG findings with actual physical behaviors. This helps confirm that the abnormal motor activity (DEB) occurs during REM sleep and distinguishes RBD from other conditions that might mimic its presentation.
What are the main safety considerations when managing RBD?
Safety considerations include modifying the sleep environment to prevent injury—such as removing sharp objects, padding furniture, using bed rails or cushions, and considering separate sleeping arrangements for bed partners if necessary. Bed alarms can also be useful to alert patients and caregivers during an episode.
What broad categories of neurological disorders are most commonly linked to sleep disturbances?
Neurodegenerative disorders, stroke, and traumatic brain injury are major categories. Additionally, sleep problems occur in neuromuscular disorders, epilepsy, and conditions associated with hypersomnia.
How are neurodegenerative disorders that affect sleep typically classified based on protein pathology?
They are divided into tauopathies—characterized by abnormal tau deposition (e.g., Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia, Pick’s disease)—and alpha synucleinopathies, where misfolded alpha-synuclein accumulates (e.g., Parkinson’s disease, diffuse Lewy body dementia, multiple system atrophy).
What distinguishes mild cognitive impairment (MCI) from early dementia?
In MCI, cognitive deficits are typically limited to one domain and do not cause major interference with daily activities, whereas early dementia involves impairments in multiple cognitive domains with substantial functional decline.
What are the hallmark neuropathological features of Alzheimer’s disease (AD)?
AD is characterized by extracellular amyloid-β plaques and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. Amyloid deposition may precede tau pathology in some cases.
How do sleep disturbances evolve over the course of Alzheimer’s disease?
Early on, patients experience disruption of sleep-wake rhythms, increased nocturnal awakenings, and a reduction in deep (stage N3) sleep. In later stages, there is a marked reduction in REM sleep, longer REM latency, and excessive daytime sleepiness.
What is “sundowning” and why is it significant in patients with dementia?
Sundowning refers to the worsening of behavioral disturbances (such as agitation or confusion) during the late afternoon or evening. It is a common issue in advanced dementia and often contributes to patient institutionalization.
What are the key sleep-related problems observed in Alzheimer’s disease?
Common issues include insomnia, circadian rhythm sleep-wake disorders, obstructive sleep apnea (OSA), and daytime sleepiness. Medication side effects can also exacerbate these disturbances.
How do cholinesterase inhibitors used to treat AD affect sleep?
While these medications (e.g., donepezil, rivastigmine, galantamine) help improve cognitive function by increasing acetylcholine, they can also lead to increased REM sleep and may cause insomnia, nightmares, or vivid dreams.
What is memantine and how does it function in AD treatment?
Memantine is an NMDA receptor antagonist that helps reduce excitotoxicity from excessive glutamate activity. It is used for moderate to severe AD and can be combined with cholinesterase inhibitors, although it may cause side effects such as hallucinations and dizziness.
What new therapies target amyloid deposition in the brain, and what are their risks?
Aducanumab and lecanemab are monoclonal antibodies designed to remove beta-amyloid. They are approved for use in early AD or MCI, but they carry risks such as amyloid-related imaging abnormalities (ARIA), which can include brain edema and microhemorrhages.
Why is it important to rule out other treatable conditions when evaluating cognitive decline?
Other conditions—such as medication side effects, hypothyroidism, vitamin B12 deficiency, depression, or undiagnosed OSA—can mimic or worsen cognitive symptoms, so they must be excluded during evaluation.
What types of sleep disorders are commonly seen in neurodegenerative diseases?
They include insomnia (problems with sleep onset, maintenance, or fragmentation), hypersomnia, sleep apnea syndromes, circadian rhythm disorders, excessive nocturnal motor activity, and REM sleep behavior disorder (RBD).
Define REM sleep behavior disorder (RBD).
RBD is a parasomnia characterized by the loss of normal muscle atonia during REM sleep, resulting in dream enactment behaviors that can lead to injuries. It is often an early indicator of neurodegenerative disease.
What is the difference between REM sleep without atonia (RSWA) and RBD?
RSWA is an objective finding on polysomnography (PSG) showing a loss of normal muscle inhibition during REM sleep, whereas RBD includes both RSWA and clinical evidence of abnormal motor behaviors during dreaming.
What are the diagnostic criteria for REM sleep behavior disorder according to the International Classification of Sleep Disorders (ICSD)?
Diagnosis requires (i) evidence of RSWA on PSG, (ii) a history or observation of sleep-related, injurious, or disruptive behaviors (i.e., dream enactment), (iii) exclusion of epileptiform activity during REM sleep, and (iv) ruling out alternative explanations such as other sleep disorders or medications.
Which brainstem structures are key in producing normal muscle atonia during REM sleep?
Critical regions include the subcoeruleus (or sublaterodorsal) nucleus, medullary magnocellular reticular formation (MCRF), pedunculopontine nucleus (PPN), laterodorsal tegmental nucleus (LDTN), and the locus coeruleus/subcoeruleus complex.
How have animal studies (in cats and rats) contributed to our understanding of REM sleep and RBD?
Animal studies have demonstrated that normal REM sleep atonia is produced by active inhibition of spinal motor neurons via specific brainstem circuits. Lesions in these areas result in RSWA and behaviors that mimic RBD, leading to models like the “flip-flop” switch for REM regulation.
What is the “flip-flop switch” model in REM sleep regulation?
This model proposes that REM sleep is controlled by mutually inhibitory interactions between REM-on regions (such as the sublaterodorsal nucleus) and REM-off regions (like the ventrolateral periaqueductal gray and lateral pontine tegmentum), ensuring rapid transitions between sleep states.
What is the prevalence of RBD in Parkinson’s disease and related synucleinopathies?
Approximately 33% of Parkinson’s patients have RBD on PSG, with up to 60% showing RSWA. In multiple system atrophy, RBD is seen in about 70% of patients, and in diffuse Lewy body dementia, up to 95% of patients exhibit RBD.
How is RBD linked to the development of neurodegenerative diseases?
Longitudinal studies indicate that a significant proportion of individuals with idiopathic RBD eventually develop a synucleinopathy, such as Parkinson’s disease, Lewy body dementia, or multiple system atrophy, often over a 10- to 16-year period.
What are some early non-motor signs of Parkinson’s disease that can precede motor symptoms?
Early indicators include loss of smell (hyposmia), constipation, mood disturbances, and sleep abnormalities such as RBD, which may appear years before classic motor signs.
How does the misfolding of synuclein protein contribute to neurodegenerative pathology?
Normally soluble synuclein becomes misfolded and aggregates into insoluble deposits. In Parkinson’s disease and Lewy body dementia, these deposits occur primarily in neurons (especially in dopaminergic pathways), whereas in multiple system atrophy they are found mainly in glial cells.
What are the primary motor features of Parkinson’s disease?
Motor symptoms include bradykinesia (slowness of movement), a characteristic “pill-rolling” resting tremor, cogwheel rigidity, and postural instability that typically appears in later stages.
What non-motor symptoms are common in Parkinson’s disease and related synucleinopathies?
Non-motor issues include cognitive impairment or dementia, mood disorders, psychosis, autonomic dysfunction (e.g., postural hypotension, bladder issues), constipation, dysphagia, drooling, and various sleep disturbances (insomnia, RBD, daytime sleepiness).
How does diffuse Lewy body dementia (DLBD) differ from Parkinson’s disease in its clinical presentation?
DLBD generally presents with earlier and more pronounced cognitive impairment, spontaneous visual hallucinations, and more symmetrical motor symptoms compared to Parkinson’s disease, along with a shorter survival time.
What does the term “parkinsonism” encompass?
Parkinsonism refers to a group of symptoms that include tremor, rigidity, bradykinesia, and postural instability. These features can be seen in idiopathic Parkinson’s disease as well as in atypical syndromes like PSP, CBD, DLBD, and MSA.
What unique sleep disturbances are observed in progressive supranuclear palsy (PSP)?
PSP is associated with very severe sleep-maintenance insomnia, a drastic reduction or absence of REM sleep, prolonged REM latency, and frequent nocturia. In addition, patients often show impaired vertical eye movements during REM sleep on PSG.
How is corticobasal degeneration (CBD) characterized in terms of motor and cognitive function?
CBD typically presents with progressive asymmetrical rigidity, apraxia (difficulty executing learned movements), and the alien limb phenomenon—where a limb may move involuntarily and feel foreign to the patient.
What are the distinguishing features of frontotemporal dementia (FTD) compared to Alzheimer’s disease?
FTD often begins with marked personality and behavioral changes (such as disinhibition and social decline) rather than memory loss, and imaging typically reveals frontal or anterior temporal atrophy.
What is Pick’s disease and how is it diagnosed?
Pick’s disease is a form of frontal lobe dementia that usually presents early with speech and language difficulties (progressive aphasia). Definitive diagnosis requires identifying Pick bodies—tau protein aggregates found in the brain.
What treatment strategies are used to manage insomnia in patients with Alzheimer’s disease?
Management includes strict sleep hygiene (daytime structured activities, exposure to natural light, a quiet sleep environment) and, in some studies, low-dose trazodone or prolonged-release melatonin. However, hypnotics are used with caution due to risks in dementia.
How does continuous positive airway pressure (CPAP) benefit patients with Alzheimer’s disease who have obstructive sleep apnea (OSA)?
CPAP can improve sleep quality, mood, and may slow cognitive decline by ensuring proper oxygenation and reducing sleep fragmentation in patients with OSA.
What factors contribute to medication-induced insomnia in AD?
Medications such as donepezil (a cholinesterase inhibitor) have been associated with insomnia, nightmares, and vivid dreams—often managed by adjusting dosing (e.g., using morning doses) or considering alternative therapies.
What are some potential biomarkers under investigation for early detection of neurodegenerative disorders in patients with RBD?
Researchers are exploring olfactory testing, color vision assessments, transcranial ultrasound of the substantia nigra, and evaluations of autonomic function as early biomarkers.
Why is the identification of RSWA on polysomnography important in the context of sleep disorders?
RSWA (REM sleep without atonia) is the key electrophysiological abnormality in RBD and can serve as an early indicator—even in patients who do not yet show overt dream enactment behavior—potentially predicting future neurodegenerative disease.
How do non-dopaminergic systems contribute to the non-motor symptoms in Parkinson’s disease?
Losses in serotonergic, noradrenergic, and cholinergic systems are linked to mood changes, cognitive decline, and sleep disturbances, complementing the motor deficits primarily caused by dopaminergic loss.
What role does the brainstem play in the pathophysiology of RBD and related sleep disturbances?
The brainstem contains nuclei that regulate muscle atonia during REM sleep. Damage or dysfunction in areas such as the subcoeruleus, MCRF, LC, PPN, and related structures can lead to RSWA and the clinical manifestations of RBD.
How do longitudinal studies inform our understanding of the progression from idiopathic RBD to overt neurodegenerative disease?
Follow-up studies have shown that a high percentage (often over 80%) of individuals with idiopathic RBD eventually develop a synucleinopathy such as Parkinson’s disease, Lewy body dementia, or multiple system atrophy, sometimes after more than a decade.
What is the clinical significance of distinguishing between “idiopathic” RBD and RBD secondary to another neurological disorder?
Idiopathic RBD may represent an early, prodromal phase of a neurodegenerative disorder. In contrast, secondary RBD occurs alongside other established neurological conditions. This distinction can guide monitoring and potential early interventions.
