sleep physiology and disorders

1. PHYSIOLOGY OF
SLEEP AND SLEEP
RELATED
DISORDERS
DR. KARRAR HUSAIN
MODERATOR : DR. PIYUSH P. SINGH

3. • Sleep is a universal behavior that has been demonstrated in every animal
species studied, from insects to mammals
• It occupy roughly one-third of human life.
• Although the exact functions of sleep are still unknown, it is clearly
necessary for survival, because prolonged sleep deprivation leads to severe
physical and cognitive impairment and, finally, death.
• Sleep is particularly relevant to psychiatry, because sleep disturbances
occur in virtually all psychiatric illnesses and are frequently part of the
diagnostic criteria for specific disorders

4. • Sleep is defined as a state of decreased awareness of environmental
stimuli that is distinguished from states such as coma or hibernation by
its relatively rapid reversibility.
• For clinical and research purposes, sleep is generally defined by
combining behavioral observation with electrophysiological recording

5. PHASES OF SLEEP
• A REM (RAPID EYE MOVEMENT) SLEEP
• B NREM (NON-RAPID EYE MOVEMENT) SLEEP

6. NORMAL SLEEP STAGES
• NREM sleep is divided in to four stages according to changes in
biophysiological changes
• NREM sleep is followed by REM sleep
• sleep pattern is usually NREM sleep stages 1 to 4 followed by REM
sleep

8. NREM SLEEP
• NREM (non rapid eye movements) consists of relatively long stretches
of dreamless sleep in contrast to REM sleep.
• Eye movements in NREM sleep are slow and rolling in contrast to
REM sleep, in which the eye movements are rapid and conjugate

9. NREM SLEEP-CHANGES IN EEG
AND CONSCIOUSNESS
(CEREBRAL FUNCTION)
• Divided into four stages
• Stages are divided according to the depth of unconsciousness
• Greater depth of unconsciousness as sleep progresses from stage 1 to 4
• EEG becomes progressively slower and shows higher-voltage pattern
( also called slow wave, delta wave )

10. • Stage I sleep, characterized by loss of alpha activity and the appearance
of a low-voltage mixed frequency EEG pattern with prominent theta
activity
• Eye movements become slow and rolling, and skeletal muscle tone
relaxes
• Motor activity may persist for a number of seconds during stage I

11. • After a few minutes of stage I, sleep usually progresses to stage II,
which is heralded by the appearance of sleep spindles (12 to 14 cps)
and K complexes (high-amplitude negative sharp waves followed by
positive slow waves) in the EEG

12. • Stage II is generally followed by a period comprised of stages III and
IV. Slow waves (≤2 cps in humans) appear during these stages,
• Stage III  20 % to 50 % of the epoch time occupied by slow waves,
• Stage IV  >50 % of the epoch showing slow wave activity.
• Stages III and IV are also referred to as slow wave sleep (SWS), delta
sleep, or deep sleep.
• Eye movements cease during stages II through IV,

13. NREM-THINKING AND BODY
ACTIVITIES
• Thinking in NREM is brief, rudimentary and readily forgotten
• Muscle tone is present
• DTR(deep tendon reflex) can be elicited
• EMG activities can be detected in chin and limb muscles

14. NREM SLEEP-AUTONOMIC
CHANGES
• Characterized by generalized decrease in autonomic activities
• Decrease in autonomic activities causes hypotension and bradycardia
• Decreased generalized metabolic activity

15. NREM SLEEP-HORMONAL
CHANGES
• Growth hormone is secreted almost entirely in NREM sleep (due to
hypothalamic-pituitary activity)
• GH is secreted in 30 to 60 minutes after the beginning of sleep
• Prolactin is secreted in NREM sleep (at the beginning of sleep)
• Cortisol is secreted in NREM sleep (late at night)

16. FUNCTION OF NREM SLEEP
• Important characteristics of NREM sleep like slow wave, decreased
generalized metabolic activities and deep unconsciousness help
revitalize the body
• Thus, NREM or slow wave sleep occurs predominantly in the early
night
• Remaining sleep becomes lighter and dream filled predominantly
characterized by REM sleep in the late phase

18. • REM sleep is described in terms of tonic (persistent) and phasic
(episodic) components
• Tonic REM sleep  EEG similar to that of stage I, which may exhibit
increased activity in the theta band (3 to 7 cps), and a generalized atonia
of skeletal muscles, except for the extraocular muscles and the
diaphragm.
• Phasic features of REM include irregular bursts of REMs and muscle
twitches

19. REM SLEEP CHARACTERISTICS
• Dreaming
• Flaccid Limb Paralysis
• Eye Movements- Rapid, Conjugate And Predominantly Horizontal
• Increased Autonomic Activities

20. REM SLEEP-CHANGES IN
AUTONOMIC ACTIVITIES
• Increased pulse
• Increased blood pressure
• Increased intracranial pressure
• Increased cerebral flow
• Increased muscle metabolism
• In men, erections
• these increase in autonomic activities are considered responsible for
increased incidence of myocardial infarctions and ischemic CVA

21. BIOCHEMICAL CHANGES IN REM
SLEEP
• Is associated with increased cholinergic activities
• Is associated with decreased dopamine, norepinephrine and epinephrine
activities
• REM sleep is enhanced by cholinergic agonists such as nicotine and
suppressed by anti-cholinergic medications

22. EEG/EMG CHARACTERISTICS OF
SLEEP
• EEG-more active than NREM similar to wakefulness. EEG shows low
voltage fast with ocular movement artifact
• EMG is silent in REM sleep corresponding to flaccid muscles
• Paradoxical to muscle tone, all other body activities are as active as the
wakefulness state in REM sleep

23. SLEEP PATTERNS-TWO
LATENCIES OF SLEEP-
DEFINITIONS
• Sleep latency- the interval to fall asleep after retiring. Normal range is
10-20 minutes
• REM latency- once asleep, normal individual enter NREM sleep and
pass in succession through four stages. The interval from falling asleep
to the first REM sleep is called REM latency. Normal range is 90-120
minutes
• Changes in these two latencies are helpful in diagnosing many sleep
disorders.
• Also, the conditions affecting these two latencies are different for these
two distinct latencies

24. MONITORING HUMAN SLEEP

25. • EEG, the EOG and EMG are used
• May also include additional respiratory effort and airflow sensors,
electrocardiogram (ECG), oxyhemoglobin saturation, esophageal PH,
and penile erections.
• The EEG is recorded from electrodes affixed to the scalp overlying
specific regions of the brain according to the international 10/20 system
of electrode placement.

26. • Sleep spindles and K complexes, transient EEG activity that
characterize stage 2 sleep are recorded from electrodes placed over the
central region
• The central electrode also registers the relatively high-voltage, low-
frequency activity originating from the frontal lobes during sleep stages
III and IV

27. • Electrode is placed over the occipital lobe to optimize detection of
alpha activity, a correlate of a relaxed waking state with closed eyes
• The EOG recording is used to detect REMS associated with
wakefulness and REM sleep, as well as the slow rolling eye movements
that occur during stage I sleep
• The EMG recording is used to detect tonic and phasic changes in
muscle activity that correlate with changes in behavioral state.
• EMG is recorded from electrodes attached to the chin

28. • Measuring daytime sleepiness
• Daytime sleepiness manifests as an increased propensity to fall asleep
or a decreased ability to maintain wakefulness, or both
• Sleep questionnaires, such as the stanford sleepiness scale (SSS) or
epworth sleepiness scale (ESS), are used.
• The SSS asks the individual to rate his or her current level of
sleepiness, whereas the ESS asks the individual to rate his or her
probability of falling asleep under various circumstances.

29. • Two standardized objective tests are typically used to measure daytime
sleepiness: the multiple sleep latency test (MSLT) measures the
propensity to fall asleep, whereas the maintenance of wakefulness test
(MWT) measures the ability to maintain wakefulness
• Both tests use the electrophysiological sleep monitoring techniques

30. • The MSLT consists of four or five sleep latency tests spaced 2 hours apart.
• At the start of each test, individuals are asked to lie quietly in a darkened
room and to allow themselves to fall asleep.
• The latency to sleep onset is recorded, and, if sleep does not occur within
20 minutes, the test is terminated.
• In the clinical setting, patients that fall asleep are usually allowed to sleep
for 15 minutes to determine whether they exhibit a tendency to enter REM
sleep in an abnormally short period of time.

31. • The mean sleep latency is calculated, as well as the number of tests in
which REM sleep was detected.
• A mean sleep latency of less than 5 minutes reflects excessive
sleepiness, whereas a mean sleep latency greater than or equal to 15
minutes is considered normal.
• In conjunction with other symptoms, two or more tests with REM sleep
are suggestive of narcolepsy

32. • During the MWT, individuals are placed under similar conditions to
that described for the MSLT, but, rather than being asked to fall asleep,
they are asked to stay awake.
• Although 20- to 40-minute tests are used, the 40-minute protocol has
the advantage of minimizing ceiling effects. A mean sleep latency of
greater than 35 minutes on the 40-minute MWT is considered normal

33. ORGANIZATION OF SLEEP
• Most adults need approximately 7 to 9 hours of sleep per night.
• Short sleepers less than 6 hours per night
• Long sleepers who may need 12 or more hours per night.
• In addition to genetic factors that influence daily sleep needs, age and
medical or psychiatric disorders also strongly influence sleep patterns.
• The proportion of time spent in each stage and the pattern of stages
across the night are fairly consistent in normal adults

34. • A healthy young adult typically spends approximately 5 percent of the
sleep period in stage 1 sleep, approximately 50 percent in stage 2, and
20 to 25 percent in each stages 3 and 4 and rem sleep.
• NREM-REM sleep  approximately 90 to 110 minutes.
• SWS (stages 3 and 4) is most prominent early in the night, and
diminishes as the night progresses, as SWS wanes, periods of REM
sleep lengthen, showing greater phasic activity and generally more
intense dreaming later in the night.

35. EFFECTS OF AGE ON SLEEP
• Development of EEG patterns of sleep and wakefulness begins at
approximately 24 weeks of gestational age, and differentiation into
active (REM) and quiet (NREM) sleep occurs during the last trimester.
• Newborn infants spend 16 to 18 hours per day sleeping, and premature
infants may sleep even more, Active sleep occupies approximately one-
half of their sleep time, and they tend to enter sleep through active
rather than quiet sleep.

36. • 3 to 4 months of age : babies shift to the adult-like pattern of initiating
sleep with NREM, sleep starts to become consolidated during the night.
• During early childhood, total sleep time decreases, and REM sleep
proportion drops to adult levels (20 to 25 percent).
• SWS continues to decline across adulthood and may disappear entirely
by 60 years of age

38. Disorders of latency

39. SHORTENED SLEEP LATENCY
• Alcohol and drug induced sleep
• Narcolepsy
• Sleep apnea
• Sleep deprivation

40. PROLONGED SLEEP LATENCY
• Inadequate sleep hygiene
• Psychiatric disorders-acute schizophrenia, major depression, and mania
• Restless leg syndrome

41. CAUSES OF SHORTENED OR
SLEEP ONSET REM SLEEP
• Alcohol, sedative and hypnotics
• Depression
• Narcolepsy
• Sleep apnea
• Sleep deprivation

42. DYSSOMNIA

43. DYSSOMNIAS-CHARACTERISTICS
• Patients may complain of difficulty getting to sleep or staying asleep,
intermittent wakefulness during the night, early morning awakening, or
combinations of any of these.
• Transient episodes are usually of little significance.
• Stress, caffeine, physical discomfort, daytime napping, and early
bedtimes are common factors

44. DYSSOMNIAS-CAUSES
• There are over 30 recognized kinds of dyssomnias. Major groups of
dyssomnias include:
• Intrinsic sleep disorders - 12 disorders recognized, including
• Hypersomnia,
• Narcolepsy,
• Periodic limb movement disorder,
• Restless legs syndrome,
• Sleep apnea.

45. • Extrinsic sleep disorders - 13 disorders recognized, including
• Alcohol-dependent sleep disorder,
• Food allergy insomnia,
• Inadequate sleep routine.
• Circadian rhythm sleep disorders - 6 disorders recognized, including
• Advanced sleep phase syndrome,
• Delayed sleep phase syndrome,
• Jetlag,
• Shift work sleep disorder

46. DYSSOMNIAS-TREATMENT
• In general, there are two broad classes of treatment, and the two may be
combined: psychological (cognitive-behavioral) and pharmacologic.
• In situations of acute distress, such as a grief reaction, pharmacologic
measures may be most appropriate.
• With primary insomnia, however, initial efforts should be
psychologically based

47. NARCOLEPSY
• Narcolepsy is characterized by excessive daytime sleepiness (EDS).
• A narcoleptic will most likely experience disturbed nocturnal sleep,
confused with insomnia, and disorder of REM or rapid eye movement
sleep.
• The main characteristic of narcolepsy is overwhelming excessive
daytime sleepiness (EDS), even after adequate nighttime sleep.
• A person with narcolepsy is likely to become drowsy or to fall asleep,
often at inappropriate times and places
• Four other classic symptoms of narcolepsy, which may not occur in all
patients, are cataplexy, sleep paralysis, hypnogogic hallucinations, and
automatic behavior.

48. NARCOLEPSY TREATMENT
• Treatment is individualized depending on the severity of the symptoms,
and it may take weeks or months for an optimal regimen to be worked
out.
• Complete control of sleepiness and cataplexy is rarely possible
• Treatment is primarily by medications, but lifestyle changes are also
important.
• The main treatment of excessive daytime sleepiness in narcolepsy is
with a group of drugs called central nervous system stimulants.
• For cataplexy and other REM-sleep symptoms, antidepressant
medications and other drugs that suppress REM sleep are prescribed.

49. PERIODIC LIMB MOVEMENTS
• Periodic limb movement disorder (PLMD), also called nocturnal
myoclonus, is a sleep disorder where the patient moves involuntarily
during sleep
• It is related to restless leg syndrome (RLS) in that 80% of people with
RLS also have PLMD. However, most people with PLMD do not
experience RLS
• Nocturnal myoclonus is treated by medications aimed at reducing or
eliminating the leg jerks or the arousals.
• Non-ergot derived dopaminergic drugs (pramipexole and ropinirole) are
preferred.
• Other dopaminergic agents may also be used

50. RESTLESS LEG SYNDROME
• NIH CRITERIA
(1) an urge to move the limbs with or without sensations
(2) worsening at rest
(3) improvement with activity
(4) worsening in the evening or night

51. RESTLESS LEG SYNDROME-
TYPES
• Primary RLS is considered idiopathic, or with no known cause.
• Secondary RLS often had a sudden onset and may be daily from the
very beginning
• The most commonly associated medical condition is iron deficiency
(medicine), which accounts for just over 20% of all cases of RLS.
• Other conditions : pregnancy, varicose vein or venous reflux , folate
deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy,
parkinson's disease and certain auto-immune disorders such as sjögren's
syndrome, celiac disease, and rheumatoid arthritis.
• Treatment of the underlying condition often eliminates the RLS.

52. RESTLESS LEG SYNDROME-
TREATMENT
• Treatment of primary RLS should not be considered unless all the
secondary medical conditions are ruled out
• Drug therapy in RLS is not curative and is known to have significant
side effects and needs to be considered with caution.
• The secondary form of RLS has the potential for cure if the
precipitating medical condition (iron deficiency , venous reflux
/varicose vein, thyroid, etc.) is managed effectively

53. RESTLESS LEG SYNDROME-
MEDICINAL APPROACH
• Dopamine agonists such as ropinirole, pramipexole ,
carbidopa/levodopa or pergolide
• Opioids such as propoxyphene, oxycodone, or methadone, etc.
• Benzodiazepines, which often assist in staying asleep and reducing
awakenings from the movements
• Anticonvulsants(gabapentin), which often help people who experience
the RLS sensations as painful.

55. PARASOMNIAS-WHAT, WHY
AND WHICH ?
• A physical and psychological condition or disturbance of sleep and
wakefulness caused by abnormalities that occur during sleep or by
abnormalities of specific sleep mechanisms
• Although the sleep disorder exists during sleep, recognizable symptoms
manifest themselves during the day
• Accurate diagnosis requires a polysomnogram, widely known as a
"sleep test.“
• Some common parasomnias include sleepwalking, sleep talking, sleep
terrors, nightmares, and teeth grinding

56. PARASOMNIAS-CLASSIFICATIONS
• A. Arousal-sleep terrors, sleepwalking
• B. Sleep-wake transition-rhythmic movement disorders
• C. Parasomnias with REM sleep-nightmares, sleep paralysis, and REM
sleep behavior disorders
• D. Other parasomnias- bruxism and enuresis

58. MAJOR PSYCHIATRIC CAUSES
OF SLEEP DISORDERS
• PSYCHOSIS/ SCHIZOPHRENIA
• DEPRESSION
• ALCOHOLISM

59. SLEEP DISTURBANCES IN
SCHIZOPHRENIA
• Schizophrenia, schizophreniform disorder and psychosis are associated
with both insomnias and excessive daytime sleepiness (EDS)
• Sleep studies are inconsistent because of diversities in presentations
and use of antipsychotic
• In acute schizophrenia, the sleep time is decreased and sleep latency is
increased
• In chronic schizoprenia, patients have normal sleep pattern.

60. SLEEP DISTURBANCES IN
DEPRESSION
• Associated with both insomnia and excessive daytime sleepiness (EDS)
• Sleep studies in major depression reveal some combination of
prolonged sleep latency, shortened total sleep, and increased arousals
during the night.
• Slow wave sleep is usually reduced.
• The first REM episode often occurs 60 minutes or less after sleep onset
(a short REM latency)

61. • Instead of the normal progression in duration of REM episodes across
the night, they are all of roughly equal length; and
• the first REM episode may have a particularly high number of eye
movements.
• The short REM latency has been interpreted by some to be a biological
marker of depression

62. SLEEP DISTURBANCES IN MANIA
• Sleep latency can be excessive
• REM sleep can be abolished
• Total sleep time can be reduced markedly

63. SLEEP DISTURBANCES IN
ALCOHOLISM
• Is associated with both insomnia and excessive daytime sleepiness
(EDS)
• The clinical and PSG data are variable
• They have a short sleep latency, less REM sleep and increased slow
wave sleep in the first half of night
• In the second half, they have increased REM and periods of
wakefulness.
• Alcohol withdrawal leads to insomnia.

64. SLEEP DISTURBANCE IN
NEUROLOGICAL DISORDERS

65. NEUROLOGICAL DISORDERS-
SLEEP DISTURBANCES
• Dementia
• Parkinson’s disease
• Fatal familial insomnia
• Epilepsy
• Headaches
• Other medical conditions

66. SLEEP DISTURBANCES IN
DEMENTIA
• Dementia of alzheimer’s type in moderate severity disturbs sleep-wake
cycle
• Causes nighttime thoughts
• Causes behavioral disturbances
• During the night, patient becomes confused, agitated and disoriented
• PSGS shows increased stage 1 NREM sleep, fragmentation and
decreased efficiency
• Daytime exercises and restricted nap during the daytime helps.
• Patient may need tranquilizers or sedatives

67. SLEEP DISTURBANCES IN
PARKINSON’S DISEASE
• Part of the problem is iatrogenic
• Affects the most patients as the disease advance
• Causes mainly combinations of nocturnal hallucinations, nightmares
and agitated confusion
• Other manifestations are fragmented sleep, insomnia or hypersomnia;
REM sleep behavior disorder and depression which interferes with the
sleep
• Dopaminergic drugs causes vivid dreams and visual hallucinations
• Clozapine (with minimal parkinson’s side effects ) is indicated for
serious nocturnal thought and behavioral disturbances

68. FATAL FAMILIAL INSOMNIA
• Inherited tendency to develop a progressively severe insomnia that is
refractory to medicine
• Is seen at average age of 50
• Is accompanied by neuropsychological problems like inattentiveness,
confusion and amnesia
• Thalamus undergoes atrophy in this condition
• Cerebral biopsy shows spongiform cerebral cortical changes

69. EPILEPSY-SLEEP DISTURBANCES
• Some seizures occurs primarily in sleep
• About 45% of patients with primary generalized epilepsy have seizures
in the sleep
• Sleep deprivation precipitates seizures in the susceptible patients.
• Obtaining an EEG after enforced sleep deprivation elicits variety of
spike-and sharp activities in more than one third of epileptics
• Anticonvulsants promote normal sleep
• Anticonvulsants raise the efficiency of sleep
• Even at therapeutic level, the anticonvulsants can also lead to excessive
daytime sleep (EDS)

70. OTHER MEDICAL DISORDERS
THAT DISTURB SLEEP
• Cardiovascular diseases-angina pectoris and myocardial infarctions
causes disturbances of REM sleep
• Thrombotic CVA causes disturbances in the NREM sleep
• Attacks of asthma, exacerbation of COPD and GERD and peptic ulcers
tend to develop during the sleep

71. THANKYOU

72. REFERENCES
• HARRISON'S PRINCIPLES OF INTERNAL MEDICINE, 18E
• KAPLAN AND SADOCK'S COMPREHENSIVE TEXTBOOK OF
PSYCHIATRY 9TH EDITION
• GANONG'S REVIEW OF MEDICAL PHYSIOLOGY, 24TH
EDITION
• MEDSCAPE E-MEDICINE