Sleep Disorders in Different Diseases Sleep Disorders in Different Diseases

Indra Narang Director, Sleep MedicineDirector, Sleep Medicine

Hospital For Sick Children, Toronto

Assistant Professor, University of Toronto

Overview

Obesity Down syndrome Sickle cell disease Prader-Willi Syndrome Cardiac disease Craniofacial disorders Central apnea/hypoventilation disorders

Sleep and Down syndrome

Sleep disordered breathing (SDB) in DS constitutes 15% of all referrals at SickKids

OSA is between 30-60% 1

Central apnea/hypoventilation disorders- prevalence unclear

Non- respiratory related sleep problems in > 50% 2

Bedtime resistance Night wakenings Parasomnias Daytime sleepiness

1. Marcus CL. Paediatrics 1991, 2. Carter M. Arch Dis Childhood 2009

Sleep and Down syndrome

Parents unable to predict OSAS in DS: Prospective cohort study 2

56 subjects had a PSG and questionnaires Mean age: 42 months (range=4-63 ) 57% met criteria for OSA 69% parents who DID NOT report sleep problems:

54% had an abnormal PSG Parents who did report sleep problems:

36% had an abnormal PSG

1. Marcus CL, Paediatrics 19912.. Shott S, 2006, Arch Oto Head & Neck Surg

Marcus CL 1991 Paediatrics

Risk factors for OSA in DS1

Variable No OSA Mild-mod OSA Severe OSA

No. children 19 21 16

Age 5.7 7.4 10.5

BMI 18.7 21.0 23.4

Snoring History 12 ( 63%) 15 (71%) 14 ( 88%)

OAHI 0.8 5.4 37.4

Previous AT 5 ( 26%) 6 (29%) 7 (44%)

Pulmonary HT 4 (21%) 6 (29%) 5 (31%)

Snoring, previous adenotonsillectomy and history of PHT could not predict OSARisk factors for OSAS were age and BMI

1. Riekstins A. ERS 2009 (abstract)

Pathophysiology of SDB in DS

Obstruction

Adenoidal hypertrophy Tonsillar hypertrophy Facial anatomy Obesity Deviated nasal septum Chronic rhinitis

Airway collapse

Circumferential pharyngeal Lateral pharyngeal Laryngeal Tongue base

Treatment for SDB in DS

30-50% have persistent OSA following adenotonsillectomy 27 patients with DS post AT with persistent OSA evaluated1

Cine MR studies performed, mean age = 9.9 years Glossoptosis in 17/27 (63%) Hypopharyngeal collapse 6/27 (22%) Enlarged lingular tonsils 8/28 (30%) Macroglossia 20/27 ( 74%) Adenoidal regrowth

Images utilised to plan surgical interventions Outcomes of further surgical intervention not known and

many DS children require NIPPV

1. Donnelly AJR Am J Roentgenol. 2004

Down Syndrome and SDB: Summary

Difficult to predict OSA in DS Traditional surgery does not cure OSA in DS Advanced imaging and surgical techniques may change the

future management Many children with DS will require NIPPV- challenging!

All DS children should have sleep surveillance Baseline PSG in all 3-4 year old children even if no history

suggestive of SDB 1, 2

1. Weijerman M, Eur J Paed 2. Shott S, 2006, Arch Oto Head & Neck Surg

Sickle Cell Disease (SCD)

Inherited hemoglobinopathies associated with vasoocclusive disease, cardiovascular and neurovascular complications

Sleep Problems: OSA - Prevalence reported to be as high as 70% 1

More severe nocturnal oxygen desaturations and higher CO2 in those with SCD and OSA compared with no-SCD OSA groups 1

Periodic leg movements reported to be 29%- more prevalent in SCD group with NO OSA 2

1. Rogers et al, J Clin Sleep Med 2010 2. Kaleyias J, J Paediatrc Hematol Oncol 2008

Sickle Cell Disease and SDB

Sick Kids data 1

41 patients (24 females) were referred with history of snoring median age 6.4 yrs 44% patients had OSA mean OAHI 18.4 History of snoring or BMI could not predict OSA But OSA was significantly associated with age < 7 years ??? Unclear if an association between OSA and VOC

F/U SCD patients had resolution of OSA with with AT

1. Al-Saleh Sleep 2009 (abstract)

Pathophysiology for OSA in SCD

Anatomical changes 2O bone marrow hyperplasia Compensatory adenotonsillar hypertrophy after splenic

infarction Racial differences in upper airway More severe oxygen desaturations and hypercapnia:

Anaemia V/Q mismatch Lung disease/abnormal lung function

Unclear as to the reason for high PLMs

Cardiac disease and SDB

Adult data suggests that SDB in the context of heart failure associated with increased morbidity and mortality

Prospective study: Cardiomyopathy patients without other morbidity known to

contribute to SDB eg DMD PSG, Echocardiogram and ENT assessment –all within 24

hours of PSG

SDB and Cardiomyopathy

Variable (21 patients) ResultsAge, years 11.6 (0.5 – 15.7)Male: Female 17:4BMI z score 0.87 (-2.0 – 2.6) History of snoring, no (%) 12 (57%)LVEF % HCMP/DCMP 72/33OAHI/hour 0.8 (0.0 – 20.7)CAI/hour 0.4 (0.0 – 3.1) Total no (%) with SDB 7/21 (33%)Mild SDB 4/7Severe SDB 3/7

Cardiac disease and SDB: Summary

Higher prevalence of SDB than expected in CM But…...not related to snoring No individual had an adenotonsillectomy One patient had a heart transplant

Resolution of SDB on PSG post transplant

Mechanisms Rostral fluid shift Altered respiratory control due to increased fluid in

pulmonary bed Increased upper airway resistance

Prader Willi Syndrome and SDB

Recognised SDB in PWS:

Increased prevalence of OSA, as high as 100% 3

Central sleep apnea/hypoventilation syndrome 4

Increased sleepiness

1. Lindgren A, 1998, Acta Ped. 2. Myers S, J Paediatr 20002. O’Donoghue FJ, J Paediatr 2005. 4. Festen D. J Clin Endocrinol Metab 2006

PWS and Sleepiness

37 PWS children with PWS1

20/37 had MSLT 5/20 had MSLT s consistent with narcolepsy

None had cataplexy But no association between obstructive AHI and MSLT

findings

1. Williams K, J Clin Sleep Med

Pathophysiology of SDB in PWS

Obesity Adenotonsillar hypertrophy Hypotonia Blunted arousal responses to hypoxia and hypercapnia Decreased Hypocretin in CSF

hypocretin synthesised in hypothalamus and promotes wakefullness and supresses REM sleep

? GH therapy

PWS, SDB and GH Therapy

Several case reports that GH related to sudden death ? Linked to co-existing URTI

6 months after GH, ? decrease in apneic events 1

Increased ventilatory response to CO2 2

Worse AHI after 6 weeks GH 3

No change in apneas/AHI after 6 months of GH 4

1. Haqq A. J Clin Endocrinol Metab 2003. 2. Lindgren A. Eur J Paediatr 19993. Miller J. J Clin Endocrinol Metab 2005. 4. Festen D. J Clin Endocrinol Metab 2006

Treatment of SDB in PWS

Adenotonsillectomy Weight loss (faciliated by GH) NIPPV Oxygen Modafinil for excessive daytime sleepiness ? Growth hormone therapy

Hypnogram: 7 month old PWS child

PSG: 2 minute screen

Oxygen - PSG: 2 minute screen

Craniofacial Malformations

Craniofacial Malformations

High prevalence of OSA due to anatomical variations High prevalence (74%) of moderate to severe OSA in children

with craniosynostosis Complete resolution of OSA not observed in the majority

following cranial, palate or adenotonsillectomy surgeries 1

Many children will require NIPPV

1. Al-Saleh S. J Craniomaxillofac Surg. 2011

Central sleep apnea/hypoventilation (CSAH)

CSAH DISORDERSDISCRETE CENTRAL APNEAS

NOCTURNAL CENTRAL

HYPOVENTILATION

Primary CSAH Disorders

Congenital central hypoventilation syndrome (CCHS) Late onset CCHS

Congenital form of severe hypoventilation Mutation in PHOX2B gene identified in 2003

Intact voluntary but not automatic control of ventilation Impaired ventilatory responses to hypoxia and hypercarbia

During sleep and even wakefulness, CCHS patients will have significant hypoventilation requiring ventilation

Official ATS Statement on CCHS Weese-Mayer DE et al, Am J Respir Crit Care Med 2010

Secondary CSAH Disorders

Management of 20 CSAH

Case KR

6 year old boy, no current known health problems

Referral: Non-urgent Snoring’ Tired, irritable and sleepy during the day,

developmentally normal

Please assess

Case KR

Night-time

Bath, book, bed Falls asleep easily in his own room and bed at 8 pm Snoring, pauses in breathing, gasping Not restless at night, does not wake up Father sleeps in his son’s room and describes many pauses

during the night

Case KR

Daytime

Tired and difficult to wake up in the morning Tired and sleepy during the day Irritable and poor concentration at school Increasing developmental concerns over the last year

Physical Examination CVS, RS, AS and CNS examination normal Tonsillar size 2+

Case KR: PSG (3 minutes)

Case KR: PSG Summary

Central apnea index 55/hour Central apneas, average duration 16 seconds associated with mild

oxygen desaturations to 85% Respiratory rate 4 – 12/minute OAHI 4.3/hour Sleep efficiency 90%, baseline SaO2 was 95% Sleep reasonably well consolidated Arousal index 20.6 Normal CO2 during night

Case KR: Investigations

Blood work – all normal Capillary blood gas – normal EKG – normal, Echo – normal PHOX 2B – no evidence for CCHS Neurology opinion – no abnormal findings Urgent referral for MRI brain

Arnold Chiari malformation Decompression surgery performed 2 days later

Case KR: PSG 6 months later

SDB and Morbidity

Sleep disordered breathing associated with Increased risk of cardiovascular disease Increased risk of glucose intolerance/diabetes Increased risk for neurcognitive deficits/behaviourial

problems Poorer quality of life

Risk magnified in the context of underlying disease

Summary

Very limited data exist for these specific high risk groups

Clinically, maintain a high index of suspicion for identifying those at risk of SDB even in absence of reported symptoms

High risk children should NOT be treated with the same paradigm as otherwise healthy children

High risk children should be evaluated pre and post intervention

When is PSG indicated in high risk groups?

Wise MS et al. SLEEP 2011;34(3):389-398

Aurora RN, et al. Sleep 2011; 34(3):379-388