7 Type Frequency (Hz) Location Normally Pathologically Alpha 8 – 13 Beta posterior regions of head, higher in amplitude on non-dominant side. Central sites at restrelaxed/reflectingclosing the eyesAlso associated with inhibition control, seemingly with the purpose of timing inhibitory activity in different locations across the brain.comaBeta13 – 30symmetrical distribution, most evident frontally; low amplitude wavesalert/workingactive, busy or anxious thinking, active concentrationbenzodiazepinesGamma30 – 100+Somatosensory cortexDisplays during cross-modal sensory processingAlso is shown during short term memoryA decrease in gamma band activity may be associated with cognitive decline
8 Type Frequency (Hz) Location Normally Pathologically Delta up to 4 frontally in adults, posteriorly in children; high amplitude wavesadults slow wave sleepin babiesHas been found during some continuous attention taskssubcortical lesionsdiffuse lesionsmetabolic encephalopathy hydrocephalusdeep midline lesionsTheta4 – 8Found in locations not related to task at handyoung childrendrowsiness or arousal in older children and adultsidlingAssociated with inhibition of elicited responses (has been found to spike in situations where a person is actively trying to repress a response or action)focal subcortical lesionsmetabolic encephalopathydeep midline disorderssome instances of hydrocephalus
14 Underlying physiology and pharmacology of sleep Normal sleepMeasurement of sleep and sleep architectureStructures and neurotransmitters involved in sleep regulation
15 How much sleep do we need? we need as much as is necessaryto stop us feeling fatigued or sleepy the next dayto enable us to perform our daily routine adequately
16 How much sleep do we need? Very variable from person to person, but 7-8 hrs commonLess than 5 hours causes problems with performance in normal young volunteers in a lab*More than 10 hours sometimes causes ‘sleep drunkenness’Many people prefer 2 sleep periods (siesta)Some people use naps to catch upMany normal people have shorter sleep on weekdays and make up the ‘sleep debt’ at weekends*Dinges et al (1997) Sleep 20(4):
17 Why do we sleep when we do? Coincidence of 3 processesCircadian process (‘body clock’) Time since last sleep (wake-dependent drive, homeostasis) Low arousal (relaxing, winding down)
18 Circadian and homeostatic drives to sleep interact wakesleepsleepwakesleepsleepwakesleepyalertnoonnoonmidnightmidnightnoonnoonmidnightmidnightnoonnoon
19 Sleep: arousal / alertness / worry High arousal can overcome other drives to sleepWorry, stimulantsLow arousal can overcome other drives to be awakeBoredom, sedating drugs
20 Measuring sleep Subjective measures Objective measures Ask the patient (include evening, bedtime, night, next day)QuestionnairesDiaryObjective measuresActigraphy – wrist-worn,measures movement
21 Measuring sleepPolysomnography - measures continuous brain activity, eye movement, muscle activity (+ respiratory variables if required)Waveforms interpreted visually to produce hypnogram of sleep stages
22 Idealized normal hypnogram: first sleep cycle awakeREMStage 1‘drowsy’ state, not perceived as fully asleepsounds seem far awayeyes roll from side to sidehappens in front of TV, in lectures etcstage 1stage 2stage 3stage 411.30pm7.30am12345678hours
23 Idealized normal hypnogram: first sleep cycle awakeK complexsleep spindleREMstage 1light sleep, ~50% of nightbreathing & heart slower, muscles more relaxed‘falling’ sensations and sleep jerks happensome imagerystage 2Stage 2stage 3stage 47.30am12345678hours
24 Idealized normal hypnogram: first sleep cycle awake‘restorative’ stage of sleep, if deprived will always be made updeep sleep, 20% of night in young adultsslower heart / breathing, muscles relaxed, paleconfused on waking straight from this stagesome imageryREMstage 1stage 2stage 3Stages 3,4(Slow wave sleep)stage 411.30pm7.30am12345678hours
25 Idealized normal hypnogram: first sleep cycle EEG like alert wakingawakelateral eye jerksREMREM (rapid eye movement sleep)cortex active (‘paradoxical sleep’)muscles paralysedeyes move rapidly from side to sideheart rate, breathing, autonomic function as awakemost dreaming (bizarre, storylike)stage 1stage 2stage 3stage 411.30pm7.30am12345678hours
26 Idealized normal hypnogram awakeREMstage 1stage 2stage 3stage 411.30pm7.30am12345678hours
27 Time asleep/time in bed Normal hypnogramREM latency70-90 min12345678hoursawakemovementREMstage 4stage 3stage 2stage 1Sleep efficiencyTime asleep/time in bed96%
34 Sleeping and waking – what goes wrong insomnianot enough sleep or sleep of poor qualityhypersomniaexcessive daytime sleepinessparasomniaunusual happenings in the nightother, eg:circadian rhythm disordersrestless legs syndromeFull classification in ICSD (2001) International Classification of Sleep Disorders - Diagnostic and Coding Manual, American Academy of Sleep Medicine, Chicago.
35 Sleeping and waking – what goes wrong insomnianot enough sleep or sleep of poor qualityhypersomniaexcessive daytime sleepinessparasomniaunusual happenings in the nightother, eg:circadian rhythm disordersrestless legs syndromeFull classification in ICSD (2001) International Classification of Sleep Disorders - Diagnostic and Coding Manual, American Academy of Sleep Medicine, Chicago.
36 What is insomnia? A+B+C A Difficulty - initiating sleep, - maintaining sleep,waking up too earlyorsleep is chronically non-restorative or poor in qualityBOccurs despite adequate opportunity and circumstances for sleepCAt least one form of daytime impairmenti. Fatigue or malaiseii. Attention, concentration, or memory impairmentiii.Social or vocational dysfunction or poor school performanceiv.Mood disturbance or irritabilityv.Daytime sleepinessvi.Motivation, energy, or initiative reductionvii.Proneness for errors or accidents at work or while drivingviii.Tension, headaches, or gastrointestinal symptoms in response to sleep lossix.Concerns or worries about sleepSeverity and duration criteria in DSM IV, ICD-10, ICSDInternational Classification of Sleep Disorders (ICSD)
37 Diagnosing insomnia:Preliminary questions for eliminating other sleep disorder as primaryAre you a very heavy snorer? Does your partner say that you sometimes stop breathing at night? (obstructive sleep apnoea syndrome (OSAS))Do your legs often twitch and can’t keep still in bed? Do you wake from sleep with jerky leg movements? (restless legs syndrome - RLS, periodic limb movements in sleep - PMLS)Do you sometimes fall asleep in the daytime completely without warning? Do you have collapses or extreme muscle weakness triggered by emotion, for instance when you’re laughing? (narcolepsy)Do you tend to sleep well but just at the “wrong times”; and are these sleeping and waking times regular? (circadian rhythm sleep disorder; evidence also from sleep diary)Do you have unusual behaviours associated with your sleep that trouble you or that are dangerous? (parasomnias)BAP consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders 2010
38 Why treat insomnia? Impaired quality of life Impaired daytime performance (objectively measured), accidents at work, road accidents↑ absenteeism (associated with 13.6% of DOR - Hajak et al, 2011)↑ risk of hypertension↑ risk of first episode/relapse of depression
39 Algorithm for treatment of insomnia: Wilson et al. 2010 BAP Guidelines
40 Individual hypnotic drugs (efficacy) Significantly different from placeboSleep onset latencyTotal sleep timeWake time after sleep onsetSleep qualitySelf-ratedPSGSelf-ratedPSGSelf-ratedPSGSelf-ratedtemazepam()*()*lormetazepamzopiclonezolpidemNozaleplonNoNoNoNoeszopicloneramelteon(week 1 only)NoPR melatoninNot measuredNoNot measuredNoPSG = polysomnography* formulation changed since studies, longer absorption timewith current tablet cf gel capsule previous formulation
41 Adverse effects of hypnotics1 Dose dependent effects on cognitionNEXT-DAY DRIVINGEpidemiology studies show that road accidents increase with benzos and zopiclonedeficits in driving simulator performance with benzos and zopicloneno reported effects of zolpidem, zaleplon, PR melatoninREBOUND (worsening of sleep after stopping)except zaleplon, melatonin, ramelteon1. Baldwin et al. J Psychopharm :
42 Benzodiazepine Dependency Primary care attendees (n=1048)1Self rated Severity of Dependence ScalePrevalence = 47%Random community sample of over 65’s (n=2785)25.4% taking benzodiazepinesOf these:9.5% met DSM criteria for dependency43% self reported being dependentDe las Cuevas et al. 2003Voyer et al. 2010
43 Hypnotics, excess mortality and dementia Prospective study (20yr) in Sweden 1regular hypnotic use ↑ all-cause mortality riskhazard ratios: men 4.54 ( ) / women 2.03 ( )high association with suicideRetrospective study in US 2prescription of hypnotic increased hazard ratio > threefoldeven if < 18 pills prescribed p.y. (dose response association)applied to several common hypnotics incl. antihistaminesfor high users: ↑ incident cancer, RR: 1.35 ( )Prospective 15yr study in France3New use of BZs associated with HR 1.6 ( ) for dementia1. Mallon et al, Sleep Med. 2009; 10(3):2. Kripke, BMJ 2012;2:e3. Billioti de Gage et al. BMJ :e6231
44 Hypnotics – duration of treatment RecommendationUse as clinically indicated (A)To stop medication try intermittent use at first if it makes sense, then try to stop at regular intervals – say every 3-6 months depending on ongoing life circumstances and with patient’s consent (D)CBT during taper improves outcome (A)
45 Cognitive-behavioural therapy works in chronic insomnia Suggested behaviorsNo clock-watchingBedroom for sleepingScheduling time for planning, worrying etc early eveningBehavioral techniquesSleep restrictionParadoxical intentCognitionsWorking on attitudes and beliefs about sleepChanging negative automatic thoughts re:not falling asleep nowdire consequencesSleep remained improved 1y later & 84% of patients were drug freeEspie et al, Behav Res Ther, 2001; 39(1):45-60
46 Sleeping and waking – what goes wrong insomnianot enough sleep or sleep of poor qualityhypersomniaexcessive daytime sleepinessparasomniaunusual happenings in the nightother, eg:circadian rhythm disordersrestless legs syndromeFull classification in ICSD (2001) International Classification of Sleep Disorders - Diagnostic and Coding Manual, American Academy of Sleep Medicine, Chicago.
47 Hypersomnia - excessive daytime sleepiness Common causeslack of sleep without any underlying disease (insufficient sleep syndrome)depression, neurological disorders, drug effectsCaused by primary sleep disorderfragmentation of nocturnal sleep(e.g. by breathing related disorders such as obstructive sleep apnea, movement disorders or parasomnias)intrusion of sleep phenomena into the awake state (e.g. in narcolepsy)disturbances of circadian rhythms (e.g. in delayed sleep phase syndrome, shift work sleep disorder).
48 Treatment of hypersomnia: Modafinil wakefulness-promoting drug used to reduceexcessive daytime sleepiness in narcolepsy 1restores alertness only moderatelymode of actionreduces cortical GABA (catecholamine-dependent)2increases histamine in TMN (indirectly)3increases extracellular glutamate4 (also indirectly5)1. Wise et al., Sleep, 2007; 30(12):2. Tanganelli et al., Eur J Pharmacol. 1995; 273(1-2):63-71.3. Ishizuka et al., Neurosci Lett. 2003; 339(2):143-6.4. Ferraro et al., Neurosci Lett. 1998; 253(2):135-85. Perez de la Mora et al., Neurosci Lett. 1999; 259(3):181-5.
49 Sleeping and waking – what goes wrong insomnianot enough sleep or sleep of poor qualityhypersomniaexcessive daytime sleepinessparasomniaunusual happenings in the nightother, eg:circadian rhythm disordersrestless legs syndromeFull classification in ICSD (2001) International Classification of Sleep Disorders - Diagnostic and Coding Manual, American Academy of Sleep Medicine, Chicago.
50 Parasomnias Non-REM sleep REM sleep Night terrors SleepwalkingConfusional arousalsBruxismEnuresisSleep startsSleep talkingHead-bangingREM sleepREM sleep behaviour disorder (RBD)Sleep paralysisNightmares
51 Night terrors and sleepwalking Usually strong family and childhood historyNight terrorsrecurrent episodes of abrupt awakening, usually in first third of night, usually with a screamintense fear and signs of autonomic arousalunresponsiveness to comfortingno detailed recallcause significant distressincidence ~ 2% adultsSleep walkingrare to present for treatment unless injured self or otherssimilar course to night terrors, often both in same subject
52 Nightmares associated with psychotropic medications cholinesterase inhibitorsbeta-blockersSSRIs esp paroxetinelevodopaGHB
53 Treatment of nightmares Psychological treatments effective (1b)focus on guided imagery, pleasant imagesexposure - writing down dreamschanging the ‘ending’A few case series show beneficial effects of the alpha-1 adrenergic blocker prazosin in reducing nightmares related to PTSD in both military and civilian settings 1Raskind et al, Biol Psychiatry. 2007; 61(8):928-34
54 REM behaviour disorder Violent complex behaviour at nightSubject recall 80-90%2 abnormalitieslack of atonia during REM sleepincreased vividness and/or nasty content of dreams
55 REM behaviour disorder Incidence unknown (prob <1%), identified in 1980s, increasingly recognisedOlder age group, steady rise after 55Idiopathic or associated with Parkinson’s disease (~50% of PD pts) , Lewy body dementia (~70%) , multiple system atrophy (>90%)RBD may be the first manifestation of these disorders, antedating the onset of parkinsonism, cerebellar syndrome, dysautonomia, and dementia by several years.M >> F (80-90% male except for those with MSA)
56 Drugs which probably provoke symptoms of RBD all SSRIsvenlafaxinemirtazapineimipramine, clomipramine(only reported in narcoleptic patients with RBD)bisoprololtramadol
57 Drugs that relieve symptoms of RBD No prospective or controlled studiesEvidence based on case series (level IV)drugNo of patientsVery effectivePartially effectiveNo effectSide effectsclonazepam 1-4mg6779%11%10%?3855%32%13%35%11082%17%1%25%melatonin 3 -12mg6N=5N=115N=3N=10N=214N=6N=4
58 Sleep paralysisIntrusion of REM atonia (and sometimes dream imagery) into awake stateIsolated prevalence ~3% (?) lifetime, unknown current, 20% in panic disorder and GADMay be genetically determinedExacerbated byirregular sleep routine /sleep deprivationalcoholanxiety / tension
59 Treatment of sleep paralysis No proven treatmentClinical experience: improved bybetter sleep hygiene (inc. alcohol)reduced anxietypractical strategies for signalling to partner - sensory input stops it
60 Sleeping and waking – what goes wrong insomnianot enough sleep or sleep of poor qualityhypersomniaexcessive daytime sleepinessparasomniaunusual happenings in the nightother, eg:circadian rhythm disordersrestless legs syndromeFull classification in ICSD (2001) International Classification of Sleep Disorders - Diagnostic and Coding Manual, American Academy of Sleep Medicine, Chicago.
61 Circadian rhythm disorders Sleep disorders where there is a mismatch between circadian rhythms and required sleep-wake cyclesleeplessness when trying to sleep at a time not signalled by the internal clockexcessive sleepiness when needing to be awakeSome circadian disorders (jetlag and shift work disorder) are due to an individual lifestyle, including work and travel schedules, that conflicts with the internal clock.Others are:delayed sleep phase syndrome: difficulty falling asleep till early hours and preferred late waking up timefree running sleep disorder where there is a daily increment of sleep and wake times (getting later each day).Much rarer– advanced sleep phase syndrome61
62 Restless legs syndrome (i) an urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs;(ii) the urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting(iii) the urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues;(iv) the urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night.(There may also be periodic limb movements in sleep - stereotyped jerks of legs or less often arms, occurring every seconds during sleep and sometimes causing arousal from sleep)62