Disorders of consciousness and sleep disorders

doc. MUDr. Valja Kellerová, DrSc.

Department of Neurology

Contents

• Brainstem reticular formation disorders

• Pathophysiology of coma

• Neurological examination of the comatose patient

• Sleep disorders, classification

• Narcolepsy, cataplexy

• Hypersomnia, sleep apnoea syndrom

• Parasomnias

Brainstem reticular formation (RF)

• descending reticular system

– inhibitory system in medulla oblongata, suppresses motion, reflexes, muscle tone

– facilitatory system in the whole brainstem, facilitates movements, exaggerates reflexes

• ascending reticular activating system

Descending reticular system

• inhibitory stimuli from:

– suppressor cortical regions– basal ganglia – anterior parts of cerebellum

disorder: decerebrate rigidity

• facilitatory stimuli from:

– vestibular nuclei– proprioceptive stimuli

disorders: cataplexy

sleep paralysis

Pathophysiology of decerebrate rigidity

Descending reticular system – inhibitory - disorder: decerebrate rigidity

• in extensive midbrain lesion, the inhibitory syst. in medulla oblongata does not obtain stimuli from the upper parts and so facilitatory system prevails:

• hypertonicity, opisthotonus, clenched jaw, extension of the arms and legs, internal rotation of the arms

• obtained:– tonic neck reflexes – oculocephalic reflex

Mumenthaler 1990

Ascending reticular activating system

• activates the cortex, maintains alert wakefulness

• clinical signs of a lesion:

– sleep disorderso pathological sleepiness (lowered function)

o insomnia (irritation)

– disorders of consciousnesso coma (lowered function)

o generalized epileptic seizures (irritation)

Ascending reticular activating system

Visual stimuli

Trigeminal stimuli

Auditory stimuli

Sensory stimuli

RF

Pathophysiology of coma

A conscious state depends on intact:

•cerebral hemispheres•the ascending reticular activating system in the brain stem (midbrain, hypothalamus, thalamus)

•interconnections between upper brain stem and hemispheres (ascending projections from the reticular formation toward the cerebral cortex)

Pathophysiology of coma

Impairment of conscious level:

• diffuse hemisphere damage• brain stem involvement• involvement of the long tracts

between the brain stem and the cortex (concussion, diffuse axonal injury)

• při postižení kmene

Lindsay

Impairment of conscious level – lesion location (Lindsay et al., Neurology and neurosurgery illustrated, 1991):

diffuse hemisphere damage (not small focal lesions)

bilateral thalamic lesion

supratentorial mass - s tra transtentorial herniation

infratentorial mass lesion - brain stem compression

brain stem lesion or from tonsillar herniation (involving reticular system) (indirectly)

No

Impairment of conscious level – brain stem lesion involving reticular formation:•in diencephalon (thalamus)•in midbrain – tegmentum - alpha coma (rare)

nc. - coma

(tr. corticospinalistr. corticobulbatis)

Alpha coma

Duffy F.H. 1989

Apallic syndrome (vegetative state):

• severe bilateral involvement of the cortex or the subcortical white matter (decortication, „a-pallium“ = „without cortex“)

• brainstem functions are preserved

• manifestations:

– coma vigile– primitive reflexes – sucking, grasping and

oral automatisms are prominent

– focal findings (pyramidal), posture: flexed arms,

or global cerebral dysfunction

Coma vigile = syndrome (a part of the

apallic syndrome). Clinical findings:• Disorder of consciousness: no perception, no

reaction to commands, no awareness of the environment, no self-awareness

• wakeful appearance, with eyes open, arousal• no purposeful or voluntary responses to stimuli • sleep-wake cycles are preserved• the patient lies passively without moving and

without speaking (akinetic mutism)• after recovery – amnesia• persistent vegetative state – persists for 1 month,

permanent – for 3 months (or 1 year, after trauma)

Examination of the comatose patient• Disorder of consciousness is

– a true medical emergency– the diagnostic problem, the goal - to distinguish

the cause (structural, focal or diffuse - toxic or metabolic – symmetrical)

• The initial assessment:– vital functions (respiration, circulation),

appearance…(the head – marks of trauma?...) – history (trauma, previous illnesses, epilepsy, alcohol…)

– information about farmacological influences:• sedatives• analgetics (miosis)• muscle relaxants

Neurological examination of the comatose patient

• assessment of the level of consciousness –GCS

• the topical diagnosis

• neurological examination:– it is impossible to examine some signs which

require the patient´s cooperation– in addition, it is necessary to examine some

reflexes which are present in coma only– assessment of brainstem functions, motor function,

muscle tone, respiration– assessment of focal findings

Examination of the comatose patient

The major neurologic functions to be observed:

• level of consciousness• exam. of the eyes - pupils, ocular movements…

• diencephalic and brainstem reflexes

• other cranial nerves, reflexes, meningeal signs

• respiration

• motor function

Examination of the eyes• palpebral fissures

– symmetry and size (nn. III, VII)

– eyelids – muscle tone (open eyes – pontine lesion or n.VII)

• pupils– size: miosis – opiates? mydriasis – atropine? or

a brainstem lesion

– reactivity: the light reflex – absent – midbrain damage(pupils are fixed to light)

– symmetry: anisocoria – unilateral unreactive mydriasis - uncal transtentorial herniation

Pupillary abnormalities in brainstem lesions (Plum F., Posner J.B., 1972)

miosis, 2mm

1mm, reactive

mydriasis, 6mm

tegmental, 4-5mm

Examination of the eyes - ocular movements

• position of the eyes at rest:– dysconjugate horizontally - strabismus (III, IV, VI),

vertically - skew deviation – conjugate deviation of the eyes

• ocular movements– spontaneous (involuntary)

• slow roving eye movements (conjugate or dysconjugate) – intact brainstem

• rare: ping-pong movements (fast), ocular dipping (slow-fast), ocular bobbing (fast-slow), opsoclonus (fast, irregular)

– reflex eye movements (conjugated)

Diencephalic and brainstem reflexes

• Reflex eye movements (vestibular stimulation):

–the oculocephalic (or “doll´s head”) reflexes (present only in coma)

• horizontal – rapid rotation of the head – the eyes move in the opposite direction (looking forward all the time)

absent – pontine lesion

• vertical – passive flexion or extension of the neck

– the oculovestibular (vestibuloocular or caloric) reflex

The oculocephalic reflex (horizontal)

Hopkins

Diencephalic and brainstem reflexes -Reflex eye movements:–the oculovestibular or caloric reflex – the ice-cold water, instilled into the external auditory canal, causes tonic deviation of the eyes toward the side of the stimulus (in the comatose patient, with intact brainstem)

Other diencephalic and brainstem reflexes

• the ciliospinal reflex – pupillary dilatation (1-2 mm) in response to a painful stimulus absent – diencephalic lesion

• the frontoorbicular (glabellar, nasopalpebral) reflex:tapping between the eyes – blinkingabsent – diencephalic or brainstem lesion

it habituates to repeated stimuli – disappears – cortex is intactit does not habituate – persistent contaction or blepharospasmus - in

apallic syndrome

Other diencephalic and brainstem reflexes

• the oculo-cardiac reflex: compression of eyeballs slows down

the heart rateabsent in medulla oblongata lesion

• the corneal reflex - absent in pontine lesion

• the masseter reflex - absent in pontine lesion

• the gag reflex - absent in medulla oblongata lesion

Respiration: abnormal respiratory patterns (Plum F., Posner J.B., 1972)

(Plum F., Posner J.B., 1972)

cerebral hemispheres

Lesions:

midbrain

pons

pons

medulla oblongata

Patterns:

Cheyne-Stokes

Central neurogenic

apneusis

cluster

ataxic

Respiration

• Central respiratory disorders can have localizing significance, but

• if the patient is hypoventilating, intubation with assisted respiration should be considered

Motor function• Assessment: (asymmetry – paresis)

– spontaneous movements– posture– muscle tone– movements after a painful stimulus: compression of

the supraorbital ridge the nail bed the sternum

Decorticate and decerebrate posture• Decorticate posture (rigidity):flexion and adduction of the arms,(flexion of the wrists, fingers,)

extension (and plantar flexion)

of the legs• Decerebrate posture (rigidity): extension, adduction

and internal rotation of the arms, extension of the legs

Netter

Other postures

• Mixed decerebrate rigidity - extension, adduction and internal rotation of the arms,

hypotonia (or atonia) of the legs – lower pontine lesion

• Generalized atonia – medulla oblongata lesion

Motor function disorders Plum F., Posner J.B., 1972Lesions: Motor

response:

pons

midbrain

hemispheres, diencephalon bilateral

unilateral, hemisphere

abnormal flexor response

abnormal extensor response

mixed response

Rostrocaudal (craniocaudal) deterioration

• is the progressive decline in neurological status due to more caudal propagation of the lesion or downward displacement of the brainstem

• consequence of central herniation• cause: a supratentorial space occupying mass

(tumor, hemorrhage or edema)• Important: to recognize rostrocaudal

deterioration early in order to institute therapy to prevent progression (against edema, operation, decompressive craniectomy…)

Rostrocaudal deterioration• Levels of deterioration:

– Cortical - subcortical– Diencephalic– Midbrain (often due to herniation of the uncus of the

medial temporal lobe)

– Pontine– Medulla oblongata

The deterioration at the certain level of the brainstem is accompanied by disorders of all higher levels.

Regression of the damage – reparation (repair) is anterograde

Sleep – two states:• Non-rapid eye movement (non-REM) sleep

(synchronous, slow wave sleep) – 4 stages:– stage 1 – drowsiness (somnolence): in EEG alfa,

beta, theta waves– stage 2 – light sleep: in EEG theta waves, sleep

spindles, K-complexes– stage 3 – deep sleep: in EEG theta a delta– stage 4 – deep sleep: in EEG delta

• Rapid eye movement (REM) sleep (paradoxical): in EEG a low voltage record with mixed frequencies, dominated by fast activity

Sleep cycles• Duration about 80-120 minutes• NREM sleep: 60-90 minutes• REM sleep: 10-30 minutes (it prolongs

during night)

Sleep disorders - classification

• the classification is necessary to discriminate between disorders

• the earliest classification systems were organized according to major symptoms:– insomnia– excessive sleepiness– abnormal events that occur during sleep

• the International Classification of Sleep Disorders (2005) combines a symptomatic presentation (as insomnia) with pathopysiology (as circadian rhythms) and body systems (e.g. breathing disorders).

Sleep disorders

International Classification of Sleep Disorders (ICSD version 2 – 2005):•insomnias• sleep related breathing disorders• hypersomnias of central origin • circadian rhythm sleep disorders • parasomnias• sleep related movement disorders• isolated symptoms• other

Sleep disorders – diagnostic procedures• the sleep history

– the chief complaint – to explain, what is meant by „insomnia“, „tiredness“, „sleepiness“

– the timing, duration, frequency, course– a detailed sleep log (2-3 weeks):

• the patient´s bedtimes• times of sleep onset• noctural awakenings• final awakenings• times of arising• the number of brief daytime naps (narcolepsy?)• snoring (obstructive sleep apnea?)….

– medication…

Sleep disorders – diagnostic procedures

• Scales, questionnaires• Electroencephalography:

– polysomnography– multiple sleep latency test (MSLT)

Epworth Sleepiness Scale (ESS)

• is a scale intended to measure daytime sleepiness by use of a very short questionnaire

• it was introduced in 1991 by Dr Murray Johns of Epworth Hospital in Melbourne, Australia

• is used to determine the level of daytime sleepiness– a score of 10 or more is considered sleepy– a score of 18 or more is very sleepy

• if you score 10 or more on this test, you should consider whether you are obtaining adequate sleep, need to improve your sleep hygiene and/or need to see a sleep specialist

Epworth Sleepiness ScaleUse the following scale to choose the most appropriate number for each situation:

0 = would never doze or sleep, no chance of dozing1 = slight chance of dozing or sleeping2 = moderate chance of dozing or sleeping3 = high chance of dozing or sleeping

Epworth Sleepiness ScaleSituation Chance of Dozing or Sleeping

Sitting and reading ____

Watching TV ____

Sitting inactive in a public place ____

Being a passenger in a motor vehicle for an hour or more

____

Lying down in the afternoon ____

Sitting and talking to someone ____

Sitting quietly after lunch (no alcohol) ____

Stopped for a few minutes in traffic while driving

____

Total score (add the scores up) ____

Excessive daytime sleepiness, EDS

• An increase in total sleep time during the 24-hr day (hypersomnia) or

• Attacks of unavoidable naps during the day, drowsiness, lowered alertness

• Epworth Sleepiness Scale score >10 • MSLT

Excessive daytime sleepiness – causes:• restriction of sleep - chronic sleep debt

(getting too little sleep, <7 hr)

• irregular sleep-wake schedules – shift workers on rapidly rotating work schedules

• diseases: – hypersomnias of central origin – hypersomnias in poor night sleep (obstructive

sleep apnea, RLS, insomnia...) – neurological diseases (Parkinson´s disease,

encephalitis, stroke, traumatic brain injury…)– psychiatrical diseases (depression, anxiety…)

• medication

Central hypersomnia

• Narcolepsy with cataplexy, without cataplexy

• Recurrent hypersomnia (Kleine-Levin sy)

• Idiopathic hypersomnia

• Behaviorally induced insufficient sleep sy

• Hypersomnia associated with other disorders (psychiatric – bipolar disorder…)

• Hypersomnia associated with use of drugs and alcohol

Narcolepsy

• is characterized by abnormal REM sleep regulation

• patients with narcolepsy have deficit of

hypocretin 1 (orexin) in the CSF and brain • genetic predisposition – narcolepsy occurs in patients

with a specific HLA subtype -the HLA-DR2 (human leucocyte antigens genotype DR2)

• the prevalence of narcolepsy is about 0.05-0.1%• it usually begins between the ages of 15 and 35 years

Narcolepsy• Monosymptomatic• Polysymptomatic, characterized by:

– Sleep attacks– Cataplexy– Sleep paralysis– Hypnagogic hallucinations

• Idiopathic, essential• Symptomatic, secondary

Narcolepsy

• brief attacks of falling asleep (several minutes)

• their onset is irresistible, imperative • they occur repeatedly, the circumstances may

be inappropriate for sleep (while standing, walking, eating, active conversation…)

• the sleep attacks may begin with REM stage, the patient falls into deep stages of sleep immediately

• falling asleep may be without drowsiness, driving a car is prohibited

Cataplexy

• Sudden loss of postural tone, partial or complete muscle weakness (sparing the muscles of respiration)

• the patient is fully awake, but cannot move• it is triggered by a strong emotion like

laughter, anger, surprise or excitement• usually lasting up to 1 min

Cataplexy

Netter

sleep paralysis

• a patient becomes transiently unable to move• before sleep onset or just after awakening• patients are fully awake • it lasts seconds to minutes• breathing is preserved

sleep paralysis

Netter

Hypnagogic halucinations

• vivid, frightening dreams, unpleasant • visual, in color, auditory, tactile, often complex• occur at the time of sleep onset or awakening

• Cataplexy, sleep paralysis and hypnagogic hallucinations are dissociated fragments of the REM state that intrude inappropriately on, or persist into, wakefulness

Narcolepsy - the diagnosis• multiple sleep latency test (MSLT):

– the whole day– polysomnography is recorded at 2-hour intervals (20´)– the patient is given 20 min to fall asleep (5 opportunities)

– the latency to sleep onset is measured– sleep stages are assessed

• diagnosis of narcolepsy:– short latency to sleep onset (less than 5-7 min)

– sleep onset REM periods (if 2 or more sleep periods contain REM sleep, then a diagnosis of narcolepsy is highly likely)

Narcolepsy - therapy

• Naps of even brief duration are helpful• Against the narcoleptic sleep attacks: stimulant

medication:– Methylphenidate– Modafinil

• Against cataplexy, sleep paralysis and hypnagogic hallucinations: drugs which inhibit REM sleep:– Tricyclic antidepressants, imipramine, clomipramine– SSRI (selective serotonin reuptake inhibitors),

fluoxetine…

Recurrent (periodic) hypersomnia

• Recurrent episodes of sleepiness lasting 2 - 28 days, at least once a year

• At the beginning of the episode, sleep lasts 18hrs and more

• Often superficial sleep stages with awakening• Intermittent, transient, with weeks to months of

normal wakefulness between episodes of EDS • Polysymptomatic form – sometimes with bulimia,

polydipsia, behavioral changes, hypersexuality – Kleine-Levin syndrome - rare

Idiopathic hypersomniaExcessive daytime sleepiness – permanent:

•The night sleep is lengthened, prolonged >10hrs• Difficult to get up in the morning (lethargic form)

• Without prolonged night sleep (somnolent form)

•Polysomnography – normal sleep patterns •sleep drunkenness – an inability to fully awaken in the morning, with reduced cognitive and motor abilities for about 30 min, with cerebellar signs •Daily sleepiness is not so imperative•Hypersomnia may be also secondary, symptomatic – the lesion is in the floor of the 3rd ventricle

Sleep apnea syndrome, SAS• Respiratory rate fluctuates during sleep with short

pauses• apnea = break of breathing longer than 10 sec• Causes:

– central (respiratory movements fail) – rare, causes: lesion in medulla oblongata (infarction, tumour…) or congenital disorder (loss of automatic breathing control)

– peripheral – obstructive – from mechanical obstruction of the airway, respiratory movements are present, loud snoring is frequent

– causes: obesity, large tongue, long soft palate, tonsillar enlargement…

Sleep apnea syndrome (obstructive):

Netter

Sleep apnea syndrome (obstructive)

• After breathing ceases, hypercapnia and hypoxia occur which stimulate respiration and awake the patient

• Sleep is fragmented, leads to daytime sleepiness• The end of apnea – sympathetic reaction with

tachycardia and arterial hypertension• Consequences: sleep apnea syndrome is a risk

factor of pulmonary and systemic hypertension and cardiac arrhythmia

Treatment of obstructive sleep apnea syndrome

• continuous positive airway pressure (CPAP) during sleep, applied through the nose, by fitting a mask to the nose, with air from a compressor

(positive pressure of 5-10cm H2O)

• Mechanical airway obstruction should be relieved by operation (uvulopalatopharyngoplasty…)

Parasomnias

• Events occurring in relation to sleep, dissociations of sleep

• Episodic, abnormal• States resembling prolonged sleep, from

which the patient can be aroused• classification of parasomnias:

– Related to non-REM sleep– Related to REM sleep

Non-REM-sleep-related parasomnias

• sleep drunkenness• In idiopathic hypersomnia• Desorientation, slowness, automatic

movements• Cerebellar signs are present• Lasts up to 30 min, amnesia• EEG: sleep stages 1-2

Non-REM-sleep-related parasomnias

• somnambulism, sleep-walking• Repeated episodes with automatic

movements or walking, eyes open, poor coordination, injury !!!

• If awakened – disoriented, confused, then amnesia

• Children aged between 4 and 12 years, often familiar occurrence

Non-REM-sleep-related parasomnias

• pavor nocturnus, night terrors• In stage III-IV of non-REM sleep• Dramatic, sudden arousal, the child cries, with

eyes open, disoriented, mydriasis, tachycardia, sweating

• amnesia, familiar

• enuresis nocturna, bed wetting• Disorder od arousal • therapy – training of micturition control

Non-REM-sleep-related parasomnias

• bruxism• Rhythmic teeth grinding during sleep• Damage of dental surfaces

• jactatio capitis nocturna• Stereotypical rhythmic movements of the head or

entire body• Infants at age 9 months

REM-sleep-related parasomnias

• nightmares• dream–anxiety attacks• Dreams with an unpleasant psychic

content, elicit awaking, often in children• Patient remembers the content of the dream

• sleep paralysis• Awake, unable to move• after awakening or before sleep onset • it lasts seconds to minutes• In narcolepsy

REM-sleep-related parasomnias

• hypnagogic hallucinations• In narcolepsy

• REM behaviour disorder• Always in REM phase, loss of muscle atonia !• Accompanied by episodes of motor behaviour• Violent behaviour, directed at the bed-partner or at

objects in the room, injury is often• Vivid, unpleasant dreams, the content correspons

with the behaviour • May be proved by polysomnography

•