Sleep

Question 1

Indications for PSG

Answer 1

• Diagnosis of OSA (gold standard)
• Craniofacial syndromes
• CSA related syndromes
• Known brainstem abnormality (ie. Chiari)
• R/O OSA in Narcolepsy work-up before MSLT

Question 2

PSG measurements

Answer 2

EEG - sleep staging
EOM - sleep staging- eye movements
chin EMG
intercostal EMG
diaphragm EMG
limb EMG - periodic leg movements - must be twitches in series to count them
ECG/HR
SpO2
Nasal Pressure (etCO2 prongs)
Airflow/ therm (mustache sticker with nasal and mouth tabs)
Chest wall
Abdo wall
Sum channel (sum or chest and abdo, not its own sensor)
TCO2 +/- EtCO2

Question 3

Stages of sleep

Answer 3

NREM1: theta waves – low amplitude, high frequency waves
NREM2: sleep spindles, K-complexes
NREM3: slow wave sleep, delta waves (high voltage, low frequency) - restorative
REM: saw tooth pattern (looks similar to alpha waves when awake), sharp eye movements, decreased. chin activity, muscle atonia – memory consolidation - more respiratory events usually (20%)
-higher amounts of REM infancy which decrease with age.

Question 4

Definition of Apnea

Answer 4

1. Drop in peak signal excursion by 90% from baseline (Airflow therm)
2. At least 2 breaths

Question 5

Definition of Obstructive Apnea

Answer 5

-Apnea criteria
-Absence of airflow
-Effort present in chest and abdo leads (might be in opposition, but not always)
-Sum channel may be zero if paradoxical breathing
-vigorous attempts to move air
+/- dec SpO2

Question 6

Definition of Central Apnea

Answer 6

-Apnea criteria
-Absent resp efforts for the duration of the event and no airflow (a decrease of 90% on SUM channel from baseline) and at least one of:
Event lasts >20 sec
if <20 sec - event lasts duration of 2 breaths AND associated with EEG arousal or >3% drop in SpO2 from BL
if <20 sec -event last duration of 2 breaths and associated with bradycardia less than 50bpm >5 sec, or less than 60bpm >15 sec —— usually < 1year old

*** transitions btw sleep cycles, post arousal, post sigh - may not meet full apnea criteria- may be okay/ physiologic-if followed by arousal or desaturation -then you score as central - bc physiologic event/ effects sleep or sats

Question 7

Definition of Mixed Apnea

Answer 7

• Need apnea criteria
  -2 breaths
  -usually the central comes first
  -central and obstructive for different parts of the event
  Dx
  -meets apnea criteria AND associated with absence of resp effort during one portion of event and inspiratory effort in another portion
  -no SpO2 decrease required

Question 8

Definition of Hypopnea

Answer 8

-Decrease in pressure from baseline of 30% (prefer to use nasal Pressure)
AND
lasting >2 breaths
AND
>3% decrease in SpO2 or associated with EEG arousal
-can be obstructive, central, or mixed

Question 9

Definition of Periodic Breathing

Answer 9

• minimum of 3 episodes of central apnea
• last for minimum of 3 seconds
• separated by maximum of 20 seconds normal respiration.

Question 10

Definition of Hypoventilation

Answer 10

pCO2, etCO2, tcCO2 >50mmHg > 25% of recording time

Question 11

Definition of Desaturation

Answer 11

Drop in SpO2 >3% from baseline or <90%

Question 12

AHI for OSA severity

Answer 12

Pediatrics (can use to <18 years old):
< 1.5 = normal
1.5 – 5 = mild
5 – 10 = moderate
>10 = severe

Question 13

Characteristics of Sleep related breathing disorders in Trisomy 21

Answer 13

• can have central and obstructive apneas
• hypopnea is still important
• Hx says they don’t snore – can not trust history of just no snoring in T21
• Screen at 4yo/ <5yo - if PSG perfect - unlikely to get more TA hypertrophy
• if symptoms do first PSG sooner
• no repeat testing unless symptoms or obese
• at risk of obesity/ OSA +/- hypoventilation in adolescence
• important to watch kids with history of PHTN that has resolved, at high risk to have recurrence of PHTN secondary to OSA.

Question 14

Characteristics of Sleep related breathing disorders in Achondroplasia

Answer 14

• Foramen magnum stenosis
• Risk of brainstem herniation or compression of the medulla
• risk of increased ICP from decreased CSF flow
• CSA can cause early death
• OSA possible – midface hypoplasia, nerve impingement
• PSG early (<1 year old) then repeat as indicated

Question 15

Characteristics of Sleep related breathing disorders in Sickle Cell Disease

Answer 15

• upper airway obstruction can occur due to racial difference in face shape – mid-face hypoplasia
• face bone medullary hematopoiesis
• adenoid and tonsil hypertrophy (increased due to compensation for asplenia)
• usually no OSA unless history of snoring or EDS
• concern with OSA and hypoxia 🡪 triggers sickling
• SpO2 may be lower at baseline bc HbS shifts your oxygen dissociation curve to the right (to promote oxygen unloading from hemoglobin – so can be even lower with sleep
• Hydroxyurea increase % HbF which shifts your curve to the left, and increases SpO2
• PSG if symptomatic: snoring +/- EDS

Question 16

Characteristics of Sleep related breathing disorders in Mucopolysaccharidoses (MPS)

Answer 16

• Group of inherited syndromes – Hurler = MPS1, Hunter = MPS2
• Hurler = macroglossia, limited mouth opening, T&A hypertrophy, laryngeal mucosal deposits, tracheal GAG deposits, neurodegenerative. Hunter similar, less severe.
• multilevel airway obstruction 🡪OSA, daytime obstruction +/- tracheostomy
• PSG indicated depending on GOC/ etc.

Question 17

Characteristics of Sleep related breathing disorders in Rett disorder (MECP2 deletion)

Answer 17

• can have CSA or OSA
• breathing abnormalities awake include (CNS dysregulation of breathing):
  
  • central apneas
  • hyperpnea - hyperventilation - hypocapnea
  • Neuro can be involved to Rx Fluoxetine, Buproprion
• can also have aspiration due to swallowing dysfunction or GERD
• ILD has been reported
• low threshold for PSG

Question 18

Characteristics of Sleep related breathing disorders in Jouberts Syndrome

Answer 18

• breathing abnormalities with sleep AND awake
  
  • central apneas
  • hyperpnea
• triad of: developmental delay, hypotonia resp rhythm abnormalities
• ciliopathy syndrome
• molar tooth sign on MRI
• PSG indicated early

Question 19

Characteristics of Sleep related breathing disorders Prader Willi Syndrome

Answer 19

• CSA more common in infancy when hypotonic/ poor feeding
  
  • should resolve with age
  • gets better with oxygen therapy
  • PSG early (<1 year old) then repeat as indicated
• OSA more common in childhood when obesity and still hypotonic
  
  • growth hormone starts need PSG pre, then after 6months on treatment
  • sleep studies and treatment needed

Question 20

Characteristics of Sleep related breathing disorders in DMD

Answer 20

-OSA – weight gain due to steroid treatment
-Hypoventilation – chest wall weakness, chest wall restriction/ scoliosis
-NIV start when ~ late non-ambulatory, FVC< 50% , MIP <60mmHg, hypoventilation awake >45mmHg
SpO2 <95% awake
-PSG when OSA Sx, concerns of hypoventilation, any SRBD

Question 21

Characteristics of Sleep related breathing disorders in SMA

Answer 21

• hypoventilation from +++ chest wall weakness - high CO2
• atelectasis from chest wall and diaphragm weakness - low SpO2
• early BiPAP improves prognosis – SMA-1 (helps prevent chest wall rigidity)
• early PSG as possible

NIV in all symptomatic infants, prepare for resp failure, helps prevent chest wall distortion, palliate dyspnea
CPAP should not be used, but with caution to maintain FRC, and when trouble syncing
Extubate from, higher pressures, to NIV, and once room air
CXR: parasol chest, ribs angle down

Question 22

Characteristics of Sleep related breathing disorders in CCHS

Answer 22

• Central chemoreceptor dysfunction
• Leads to central apneas during sleep, and prolonged breath-holding in the day
• PSG early (<1 year old) then repeat as indicated
• Avoid swimming, EtOH, drugs
• Caution with illness, bc classic tachypnea/ distress not always apparent

Vent support :
-PPV with trach in first several years of life
-possibility of decannulation and nocturnal NIV at 6-8yrs earliest
Diaphragm pacing

Question 23

Characteristics of ROHHAD

Answer 23

• Rapid onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation
• Rare disease, high mortality rate 50-60% with cardioresp arrest

No specific diagnostic test, clinical Dx

1. Excessive weight gain (20-30lbs) over 6-12mo in young child beginning 2-3yo
2. May have: neuroendocrine tumor, hyperprolactinemia, central hypothyroidism, disordered water balance (diabetes insipidus), failed GH stim test, temp dysregulation, gastric dysmotility, hypotension.
3. SRBD – OSA, CSA, abn response to CO2/ hypoventilation
   * *predisposed to cardiac arrest**

Hypoventilation is essential, but it can evolve over time, other symptoms presenting first
-may initially present only with OSA, and develop nocturnal hypoventilation + dysfunctional day-time breathing later (centrals with desaturations)

Question 24

Criteria for Type 1 Narcolepsy

Answer 24

Type 1 – A & B criteria must be met
A. daily periods of irrepressible need to sleep or daytime lapses into sleep >3mo
B. one or both of
1. Cataplexy AND a mean sleep latency of <8 minutes and 2 or more sleep onset (w/in 15 minutes of sleep onset) REM on MSLT. SOREM on PSG night before can replace one above.
2. CSF hypocretin-1 concentration, measured by immunoreactivity <110pg/mL or <1/3 of mean values in normal subjects during the day
** in children, Narcolepsy can present as excessively long night time sleep or as resumption of previously discontinued day-time napping.
** if narcolepsy type 1 suspected, but B of criteria not met, the MSLT should be repeated.

Question 25

Criteria for Type 2 Narcolepsy

Answer 25

Type 2 – A through E criteria must be met A. daily periods of irrepressible need to sleep or daytime lapses into sleep >3mo B. mean sleep latency of <8 minutes and 2 or more sleep onset (w/in 15 minutes of sleep onset) REM on MSLT. SOREM on PSG night before can replace one above. C. Cataplexy is absent (if cataplexy develops later – can chg Dx to type 1) D. CSF hypocretin has not been measured OR CSF hypocretin-1 concentration, measured by immunoreactivity <110pg/mL or <1/3 of mean values in normal subjects during the day E. Hypersomnolence and/or MSLT findings are not better explained by: insufficient sleep, OSA, delayed sleep phase disorder, effect of medications/ substances.

Question 26

Architecture of Normal Sleep

Answer 26

REM sleep = characterized by wake-like high-frequency, low amplitude, "desynchronized activity' and loss of skeletal muscle tone NREM sleep = high-voltage, low frequency "synchronized" waves with preserved skeletal muscle tonic activity

Question 27

Developmental Aspects of Sleep

Answer 27

1. Neonates and young infants spend larger amount of time in REM sleep 2. NREM sleep aka “quiet sleep” poorly developed in newborns (relative amount increases during first 3 mos) 3. With advancing age, more NREM sleep, less REM sleep 4. During slow-wave sleep, growth hormone is secreted in large amounts (sleep deprivation or disorders of sleep interfere with secretion and regulation of GH)

Question 28

Centres of Respiratory Control

Answer 28

1. Pre-botzinger complex = collection of 150-200 neurons in brain stem region responsible for generation of respiratory rhythmic activity o Rhythmically firing neurons sufficient to generate normal respiratory pattern 2. Repiratory control areas also receive afferent inputs from central and peripheral chemoreceptors, and from stretch receptors (upper airways, chest wall, lungs)

Question 29

Aspects of Sleep and Breathing During Development

Answer 29

1. Resp pattern instability during sleep is present during early life – short apneic episodes <5s are very common in prems, and their frequency is reduced in full-term newborns 2. Higher variability of HR during REM sleep (increased parasympathetic and sympathetic outflow)

Question 30

Developmental differences with neonate that accounts for emergence of sleep- associated disruption of normal gas exchange

Answer 30

1. Neonates have more difficulty switching from nasal to oral route of breathing (most = obligate nasal breathers) 2. Stronger upper airway reflexes (laryngeal chemoreflex) → can induce apnea and bradycardia 3. Increased chest wall compliance, requiring dynamic (rather than passive) maintenance of FRC 4. Paradoxical breathing, esp during REM sleep, is common in newborns because of uncoordinated interactions between chest and abdomen 5. RR is higher in neonatal period; further increases in REM to maintain FRC 6. Periodic breathing common; sleep state transitions, arousals, hypoxia, hyperthermia can enhance frequency and magnitude of periodic breathing 7. Arousal from sleep thought to be major determinant for termination of apnea; arousal deficits implicated in pathophys of SIDS

Question 31

Factors that decrease arousability in neonates

Answer 31

1. Prone position 2. Sleep deprivation 3. Pre and post-natal smoke exposure

Question 32

Where are the central chemoreceptors and what do they regulate?

Answer 32

``` Central chemoreceptors (sense changes in extracellular pH and CO2) are diffusely located in CNS ie, posterior hypothalamus, cerebellus, locus coeruleus, brain stem, etc → ventilatory response to hypercapnea (May not be fully functional/mature at birth; infants may have higher CO2 threshold) ``` Ventilatory responses related to change in blood O2 level is a complicated interaction of peripheral and central chemoreceptors (most peripheral chemoreceptor cells located within carotid bodies)

Question 33

Primary causes of Central Apneas and Hypoventilation Syndromes

Answer 33

1. CCHS 2. Late-onset CHS 3. Idiopathic hypothalamic dysfunction 4. Chiari malformation 5. Myelomeningocele

Question 34

Secondary causes of Central Apneas and Hypoventilation Syndromes

Answer 34

1. Trauma 2. Infection 3. Tumour 4. CNS-infarct 5. Asphyxia 6. Increased ICP 7. Metabolic

Question 35

What is Congenital Central Hypoventilation Syndrome (CCHS)?

Answer 35

Life-threatening disorder manifesting as sleep-associated respiratory insufficiency and impaired ventilatory responses to hypercapnia and hypoxemia - ventilation most severely affected during quiet NREM sleep state during which automatic neural control is predominant - abnormal respiratory patterns also occur during active REM sleep and wakefulness, but to a milder degree - wide spectrum of severity: mild hypoventilation during quiet sleep with good alveolar ventilation during wakefulness, to complete apnea during sleep with severe hypoventilation during waking

Question 36

Pathophysiology of CCHS

Answer 36

missing sympathetic neurons in hypothalamus acting as communication between cerebral cortex and brainstem Associated impairments in autonomic nervous system: o Hirshsprung disease o Tumors of autonomic neural crest derivatives (neuroblastoma, ganglioneuroblastoma, ganglioneuroma) o Sinus arrhythmia o Aniridia

Question 37

Genetics of CCHS

Answer 37

PHOX2B gene mutation, consists of polyalanine expansions, manifests an AD mode of transmission and de novo mutations at the first generation ● Gene is critical for ANS embryologic development ● Heterozygous mutations of PHOX2B can account for variations of ANS disorders, such as late onset CHS, hirschspung disease, and tumors of sympathetic nervous system ie. Neuroblastoma

Question 38

Diagnosis of CCHS

Answer 38

Variability of presentations, ie. Infant with pulmonary HTN; unexplained apnea or ALTEs; tachycardia, diaphoresis, cyanosis during sleep ● Wide spectrum of severity in clinical manifestations determines age of diagnosis Diagnostic criteria include: 1. Persistent evidence of sleep hypoventilation (PaCO2 >60mmhg) during quiet sleep on PSG 2. Presentation of symptoms during the first year of life 3. Absence of cardiac/pulmonary/neuromuscular dysfxn that could explain the hypoventilation Other testing can include: Hypercapnic ventilatory challenge: re-breathing incremental CO2 will reveal absent/near-absent response

Question 39

Clinical management of CCHS

Answer 39

Lifelong condition Depending on severity, pts may need ventilatory support while asleep or 24hrs/day Diaphragm pacing Surveillance for associated ANS anomalies

Question 40

Definition of Apnea of Prematurity

Answer 40

Defined as a pause in breathing >20 seconds, OR an apneic event <20 seconds associated with bradycardia or cyanosis Recurrent episodes of apnea are common in prems, with increasing incidence and severity with earlier GA Events can occur spontaneously and be attributable to prematurity alone, but can be provoked or worsened by additional insults such as infxn, hypoxemia, hyperthermia, evolving intracranial pathology Prem neonates breathe irregularly during sleep, greater breath-breath variability Central and obstructive events both reported; most common is mixed apnea

Question 41

Contributing factors for Apnea of Prematurity

Answer 41

1. Reduced respiratory drive 2. Impaired pulmonary function from lung immaturity 3. Impaired respiratory mechanics

Question 42

Natural history of Apnea of Prematurity

Answer 42

AOP generally resolves by 36-40 wks post-conceptional age but in the most premature infants (24-28 wks), apnea can persist beyond 40 wks (43-44 wks post-conceptional age)

Question 43

Pathophysiology of Apnea of Prematurity

Answer 43

1. Immaturity of central respiratory control 2. Breathing pattern more disorganized during REM sleep 3. Prems have an altered response to increased CO2 in that they respond by diminished rather than increased respiratory effort 4. Prems have a biphasic ventilatory response to a decrease in inspired O2 concentration; initially there’s a rapid increase in MV caused by peripheral chemoreceptor stimulation, followed by a decline in ventilation to baseline or below (hypoxic ventilatory depression)

Question 44

Diagnosis of Apnea of Prematurity

Answer 44

Diagnosis of exclusion; rule out associated conditions, ie. Infection, impaired oxygenation, CNS problems (intracranial hemorrhage, asphyxic episode, brain malformation), GER, temperature instability (hypo/hyperthermia), drugs (narcotics, anticonvulsants), metabolic disorders (hypoglycemia, lyte imbalance, fatty acid disorders, metabolic acidosis)

Question 45

Treatment of Apnea of Prematurity

Answer 45

CPAP ventilation Pharmacologic: methylxanthines (theophylline, caffeine) o Major MOA is through competitive antagonism of adenosine receptors which act as inhibitory neuroregulator in CNS o Shown to increase MV, improve CO2 sensitivity, decrease hypoxic depression of breathing, enhance diaphragmatic activity, decrease periodic breathing o Caffeine > theophylline: more effective in stimulating CNS and resp systems, higher therapeutic index so CNS toxicity not a problem o Toxic levels can lead to tachycardia, cardiac dysrhythmias, feeding intolerance, diuresis, seizures

Question 46

Role of CPAP in Apnea of Prematurity and OSA

Answer 46

OSA: splints open upper airway w positive pressure, decreasing the risk of pharyngeal/laryngeal obstruction AOP: beneficial by increasing FRC, improving oxygenation

Question 47

Role of oxygen in Apnea of Prematurity

Answer 47

AOP and periodic breathing resolve when O2 concentration is increased to a threshold level (improves resp stability)

Question 48

Characteristics of Obstructive Sleep Apnea

Answer 48

Characterized by repeated events of partial or complete upper airway obstruction during sleep, resulting in disruption of normal gas exchange and sleep patterns

Question 49

Night-time signs and symptoms of OSA

Answer 49

``` Snoring Paradoxical chest and abdomen motion Retractions Witnessed apnea Snoring episodes Difficulty breathing Cyanosis Sweating Disturbed sleep Restless sleep/frequent awakenings Enuresis ```

Question 50

Day-time symptoms of OSA

Answer 50

``` Mouth breathing Difficulty to wake up Nasal obstruction Recurrent ear infxns Difficulty swallowing Moodiness Daytime sleepiness Hyperactivity Cognitive problems ```

Question 51

Concerning consequences of OSA

Answer 51

``` Cor pulmonale HTN Pulmonary HTN FTT Developmental delay Death ```

Question 52

Common patient population to see OSA

Answer 52

Adenotonsillar hypertrophy Craniofacial abnormalities, Neurologic disorders affected upper airway patency Obesity

Question 53

Epidemiology of OSA

Answer 53

Peak prevalence age 2-8 yrs, possibly related to reductions in viral loads and associated adentonsillar lymphoid tissue proliferation Estimated to affect 2-3% of children Clinical history and p/e are poor predictors of disease

Question 54

Pathophysiology of OSA

Answer 54

Occurs when upper airway collapses during inspiration 1. When resistance to inspiratory flow increases or when activation of the pharyngeal dilator muscle decreases, negative inspiratory pressure can collapse the airways 2. T+A: lymphadenoid tissue will grow esp. large in children exposed to cigarette smoking, children w allergic rhinitis, asthma, recurrent viral URTIs 3. Exact pathophys remains poorly understood, but likely contribution of structural and neuromuscular variables within the upper airway

Question 55

Conditions associated with OSA

Answer 55

● Adenotonsillar hypertrophy ● Obesity ● African-American race ● Allergic rhinitis ● Asthma ● Micrognathia ● Down syndrome ● Craniofacial syndromes (Treacher Collins syndrome, midfacial hypoplasia, ● Crouzon’s syndrome, Apert’s syndrome, Pierre Robin sequence) ● Achondroplasia ● Mucopolysaccharidoses ● Macroglossia ● Sickle cell disease ● Myelomeningocele ● Cerebral palsy ● Neuromuscular disorders (Duchenne’s, SMA) ● Cleft palate repair and velopharyngeal flap ● Foreign body ● Structural anomalies, ie. Laryngotracheomalacia, subglottic stenosis

Question 56

Treatment of OSA

Answer 56

1. First line usually T+A ▪ Post-op PSG recommended for pts with additional risk factors (10-12 wks post-op) to ensure additional interventions not required 2. CPAP, BiPap 3. Other: - Dental procedures to increase width palate - Craniofacial reconstruction - Tongue wedge resection - Epiglottoplasty - Mandibular advancement - Lingual tonsillectomy - Intranasal steroid, singulair

Question 57

Why are children with OSA at risk post-op?

Answer 57

Children with OSA at risk for respiratory compromise post-op as a result of upper a/w edema, increased secretions, resp depression secondary to analgesic + anaesthetic agents, and post-op obstructive pulmonary edema High risk post-op: children <3 yrs, severe OSA, pts w additional medical conditions ie. Craniofacial syndromes Should be monitored at least 24 hrs post-op

Question 58

Short and Long Term Morbidity of OSA

Answer 58

OSA associated with a systemic inflammatory response, leading to excessive catecholaminergic release, indicative of increased sympathetic activity, promoting endothelial dysfunction Similar mechanisms induced by OSA (w concurrent obesity) promotes dyslipidemia, insulin resistance, hepatic injury Behavioural effects: restlessness, aggressive behaviour, excessive daytime sleepiness Neurocognitive deficits: decreased intellectual function, ADHD