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REM Sleep Parasomnias but Their Precise Underlying Neurobiology Remains Obscure

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REM Sleep Parasomnias but Their Precise Underlying Neurobiology Remains Obscure Parasomnias Dr Paul Reading Abstract Parasomnias represent a huge spectrum of undesirable events that arise from the sleep state or occur at the sleep/wake transition. They can reflect motor, sensory or experiential phenomena in isolation or as a combination. Most classifications of parasomnias are based on the stage of sleep from which they usually arise although, rarely, some may occur throughout the REM/non‐REM sleep cycle. Traditionally, periodic limb movements (PLM’s) and nocturnal epilepsy are considered as separate phenomena. The commonest parasomnia affects at least 10% of children and is considered a “disorder of arousal” from deep non‐REM or slow‐wave sleep. As it usually manifests initially as benign sleep‐walking, it rarely comes to medical attention and most often resolves with age through adolescence. However, when non‐REM parasomnias persist into adulthood, the behaviours can be troublesome or even violent and worthy of clinical intervention, especially if there is risk of injury. Unfortunately, treatment options remain empirical in the complete absence of clinical trial data. It is often useful to address potentially reversible factors that either increase the intensity of slow wave sleep, particularly sleep deprivation, or fragment sleep, such as severe snoring, since both these factors may fuel parasomnia activity. A strong genetic component predisposes to non‐REM sleep parasomnias but their precise underlying neurobiology remains obscure. Nightmares can be considered as a REM sleep parasomnia but REM sleep behaviour disorder and REM sleep paralysis are the two disorders most often referred to sleep clinics. The former is witnessed as aggressive or vigorous dream enactment and generally affects late middle‐aged men. Of intense interest to neurologists, it is a reliable marker for the future development of Parkinson’s disease or similar neurodegenerative conditions. Not infrequently, it leads to injury and merits long‐ term treatment, usually in the form of clonazepam or melatonin. REM sleep paralysis can be an isolated phenomenon, occasionally occurring at sleep onset and up to several times a week, typically in younger subjects. If disturbing or interfering with sleep quality, it may respond to REM sleep suppressants such as low dose tricyclic antidepressants. Many (motor) phenomena may occur at the sleep‐wake transition although very few can be considered a “disorder” as they often only adversely affect the bed partner rather than the subject. Rhythmic movement disorder of sleep, particularly head‐banging, is relatively common in children but usually resolves with age. If it persists into adulthood, the movements can evolve into body rocking or head shaking and can disturb the bed partner through most of the sleep period, even when the subject is in REM sleep. Drug treatments are rarely helpful. Learning objectives The student will be better able to: recognise the range of parasomnias and be confident of likely diagnosis after taking a thorough history judge the utility of sleep testing in the diagnosis and management of the various parasomnias appreciate the commonly used treatment options for parasomnias and the lack of controlled evidence Further reading Zadra A et al. Somnambulism: clinical aspects and pathophysiological hypotheses. Lancet Neurology. 2013;12:285‐294 Arnulf I. REM sleep behavior disorder: motor manifestations and pathophysiology. Movement Disorders. 2012;27(6);677‐689 31 Reading Parasomnias The Parasomnias Dr Paul Reading Department of Neurology The James Cook University Hospital Middlesbrough, UK The Parasomnias “undesirable events from or around sleep” can be motor, sensory or experiential Non-REM (slow wave) sleep parasomnias “disorders of arousal (DOA) ” - nocturnal confusional arousals - night terrors - sleep walking or other complex motor behaviours REM sleep parasomnias - sleep paralysis - REM sleep behaviour disorder Parasomnias at wake-sleep transition - rhythmic movement disorders of sleep 1 31 Reading Parasomnias “disorders of arousal” cataplexy; e.g. sleep walking; sleep paralysis; hypnic jerks hallucinations; e.g. narcolepsy, PD WAKE lucid dreaming NREM REM “overlap” syndromes or “ambiguous sleep” common in narcolepsy and some dementias (esp DLB) cf delirium Clinical Features of non-REM parasomnias history is key to diagnosis – rare for sleep tests to help significantly >1% of adults affected? • usually a past story of childhood “arousal disorder” - confusional arousals - sleep talking or walking - agitated night terrors positive family history (~80%) • subsequent memory for nocturnal events absent / vague • true (narrative) dream recall during event is rare only brief hallucinatory mental images / delusions common themes: - spiders, a “presence” in bedroom, - non-specific agitation, impending doom, - intense “need to escape” from bed 2 31 Reading Parasomnias • some verbal communication/interaction often possible • wide range of behaviours including complex motor acts in adults, behaviours often become goal-orientated that reflect basic drive states (e.g. eating, sex, protection) • disturbances not stereotyped, usually ~1-2 h > sleep onset coinciding with first deep slow wave sleep (SWS) period • typical frequency several / month, often with clustering • precipitating (reversible?) factors may be identified SWS sleep “promoters” : - prior sleep deprivation - drugs (zolpidem, oxybate, alcohol?) SWS sleep “fragmenters”: - uncomfortable bedroom, noise - significant snoring (partner?) - full bladder - excessive leg movements / PLM’s -anxiety Neural basis of non-REM parasomnias little scientific data no convincing lesion data or animal models neuro-developmental a “wiring problem” causing “unstable” SWS? one SPECT study Bassetti et al 2000 in sleep walking episode : - vermis (A) and post cingulate activated (B) -fronto-parietal cortex underactive (C & D) (compared to awake controls) Bassetti C et al, The Lancet 2000; 356: Pg 484‐485 3 31 Reading Parasomnias onset of event Courtesy of Prof Matthew Walker, UCL typical EEG seen in sleepwalking - frontal leads show continued delta wave (slow wave sleep) activity Night terror in 5 year-old child 4 31 Reading Parasomnias Adult non-REM sleep parasomnia mild agitation (female) Example exhibits many typical features complex (agitated) behaviours observed - eyes open, ~good navigation, verbal interaction actions inappropriate and out of character events occur soon after sleep onset - not recurrent through night no subsequent morning recollection triggered by work-related stress? positive family history 5 31 Reading Parasomnias Adult non-REM sleep parasomnia moderate agitation (male) drug treatments (if required and if no clear secondary triggers) - no controlled evidence from drug trials - little “science” to guide choices - need for a drug that mimics normal aging? - short intermittent courses preferable? . clonazepam 0.25 - 2mg . clomipramine 20 - 75mg . paroxetine 20mg . melatonin 2- 6mg . topiramate 25 – 50mg 6 31 Reading Parasomnias REM sleep parasomnias Recurrent isolated (REM) sleep paralysis voluntary muscle paralysis at wake / sleep onset (in absence of other narcoleptic symptoms) - note: 15-40% of general population have had >1 episode - episodes last seconds / minutes with full recall - usually disturbing and readily called, even years later - often aborted by sensory (tactile) stimulation - hallucinations (visual / tactile) commonly associated • rare familial form exists - typically at least several episodes a month - maternal inheritance proposed • if treatment required, tricyclics usually effective e.g. clomipramine 25-75mg nocte 7 31 Reading Parasomnias REM sleep behaviour disorder (RBD) ICSD-3 (2014) RBD characterised by abnormal behaviours [“dream enactment”] emerging during REM sleep that cause injury [to subject and / or bed partner] or sleep disruption; RBD is associated with EMG abnormalities with an excess of muscle tone or phasic EMG twitch activity during REM sleep i.e. loss of normal REM atonia and significant locomotor activation in humans, first described in detail by Mahowald and Schenck (1986) Clinical Features of RBD In RBD: . subjects generally elderly males . no clear awareness of environment - not able to navigate or use objects; - eyes usually closed . subjects do not wander around - rare to leave the bed . attacks brief, explosive, often recur - upper limbs typically involved . violence is unplanned / unintentional - victims are generally bystanders . fairly easy to arouse subjects - unpleasant or violent dream recall very common - range of behaviours may be wider than previously appreciated 8 31 Reading Parasomnias Human REM sleep behaviour disorder (RBD) vocalisation often prominent cohort study of 44 i-RBD patients recruited between 1991-2003 by 2012, 40 had developed clinical markers of neurological disease : - 16 Parkinson’s disease - 14 dementia with Lewy bodies - 1 multiple system atrophy - 9 mild cognitive impairment of 4 remaining subjects: all had >1 marker of possible Lewy body disease - abnormal DAT scan - hyposmia - substantia nigra hyperechogenicity post-mortem on 3 confirmed wide-spread Lewy body pathology percentage free of neurological disease free of neurological percentage time from i-RBD diagnosis (yrs) 9 31 Reading Parasomnias Diagnosing RBD is PSG always needed? possibly not, if history very clear or if definite parkinsonism? PSG indicated if: • clinical doubt • poor response to medication • any possibility of sleep apnoea Note : 13% of PD patients with
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