Mientras dormimos somos todos iguales Proberbio espanol

Trastornos del sueño en Enfermedades Neuro-Musculares ENMs

Guillermo do Pico MD FCCP Professor Emeritus University of Wisconsin

Porque dormimos ?

No se sabe pero -teorias:

Adaptacion/proteccion

Conservacion de energia

Restoracion

Plasticidad cerebral Memoria/Aprender

Historia 1980s

Inicio de Polysomnografia “Miedo de dormir” Una vez dormido:

hypoxemia, Apneas, sleep fragmentation

CPAP ---dormir sin interrupcion

Cerebro alerta para evitar hipoventilacion ?

Transtornos del sueno en ENMs

Hypersomnolencia

Insomnia

Trastornos respiratorios del dormir (SDB)

Transtornos del ritmo circadiano

Movimientos periódicos de las extremidades durante el dormir (PLMS) w/ w/o

Parasomnias (transtorno de conducta en REM)

Narcolepsia (baja hipocretina en FCS)

Alteraciones del sueno en ENMs

Comprobados: Mala calidad del sueno……33-96%

SDB precede fallo respiratorio diurno VNI beneficia QOL & sobrevivencia Todavia debatible Cuando evaluar con polisomnografia ? Cuando iniciar VNI ?

Calidad dormir mala = fatiga somnolencia

Primaria- Disfuncion del mecanismo central de vigilia

Secondarias:

Dolor

Limitacion de movilidad en cama

Alteracion movilidad de secreciones

Anxiedad &/or Depresion

Fragmentacion por SDB

Hypersomnolence in myotonic dystrophy I

Hypersomnolence & fatigue in 80% !!

Due to SDB = 33-77% (several studies) OSA 50% italian study

Primary central hypersomnia Myotonic Dystrophy w/ hypotalamic lesion

Narcolepsy-like syndrome with low hypocretin-1 level in CSF

“WAKE

CENTER”

WAKE SYSTEMS Two Independent Ascending Via ponto- Encephalic Junction Ventral Dorsal Orexin/ Hypocretin Neurons- LatHypoTal

Saper et al Nature 2005

LDT

PPT

(cholinergic)

VPA gray

(dopamine)

PARKINSONS

Degeneration of

Dopaminergic &

Cholinergic neurons

Myotonic

Dystrophy 1

“WAKE

CENTER”

Narcolepsy

syndrome

due to

Parkinsons Hypersomnolence

Primary=Central

Secondary: • Insomnia

• PLMNS

• Fragmentation : tremor, stiffness, pain, depression

• Drugs

Respiratory Hypoventilation – rigidity chest wall muscles

Central Sleep Apneas -vent control

L-dopa respiratory dysfunction

Oromandibular dystonia

Upper airway dysfunction---OSA?

Transtornos respiratorios del sueno en enfermedades neuromusculares

Apneas/hipopneas

Hipoventilación

Sindrome resistencia vias aereas superiores con “arousals” relacionados a esfuerzo respiratorio

Prevalence SDB in NMDs what to expect

Pattern of SDB=Severity, duration, type

Neuromuscular clinic 46%

ALS 17-76% Hypoventilation = inevitable

OSA early w/ bulbar ALS

PostPolio Syndrome 31%

Duchene’s MD in children SDB 78% OSA, CSA or pseudoCSA, Hypoventilation inevitable

Myastenia gravis OSA 60% !?

ENF NEUROMUSCULARES Factores en comun

Compromiso musculos inspiratorios Fallo Respiratorio Hipercapnico Hipoxemia

Compromiso musculos expiratorios Tos disminuida Pneumonia/ atelectasias

Compromiso vias aereas superiores Apnea obstructiva del sueno Aspiracion

Respuestas neurales disminuida

Todos peor durante el sueno

Con la Perdida del estimulo de vigilia durante el sueno normal =

Reduccion de la ventilation

NoREM cambios son marginales Metabolismo reducido

Descargas neurales disminuidas-O2/CO2

Aumento de la Resistencia en las Vias aereas superiores actividad musculos dilatadores

REM Ventilation baja 40% ! Descarga Respiratoria central disminuida

Actividad musculos respiratorios disminuida

DEMANDA VS RESPUESTA

Adulto sano

Enfermedades Neuro-musculares

Respiracion durante el dormir

Aumento de la Demanda en ENMs

Aumento del trabajo respiratorio

Resistencia vías aereas superiores (carga resistente)

Disfuncion Faringo-laringo

Compliance pared torácica o pulmones Micro-atelectasia (volumen)

Fibrosis o Aspiracion

Rigidez de la caja torácica:

• Anquilosis, cifoscoliosis

• espasticidad intercostal (Parkinsons)

• Parálisis (Quadriplejia)

Obesidad

Respuesta reducida en ENMs

Debilidad muscular (pero fatiga inusual)

tasa de progresión

distribución

Reducida compensacion de carga o a estímulos (e.g. resistencia o químicos)

Alteración quimosensibilidad O2-CO2

Enfermedad pulmonar restrictiva

Alteracion control central del sueno…….

Evolution of Ventilatory failure in NMDs

Normal ventilation REM sleep disordered

breathing nonREM + REM SDB Daytime ventilatory

failure

ALS Kyphoscoliosis Musc Dystrophy PostPolio synd

RESPIRATORY MUSCLE WEAKNESS HYPOVENTILATION

Sleep hypercapnia

bicarbonate Reduced

chemosensitivity

Awake hypercapnia

Sleep deprivation

Contributing factors

Obesity

Hypothyroidism

Hypophosphatemia

Left Ventricular failure

Obstructive Sleep Apnea

Cheyne Stokes or periodic breathing

Como y cuando evaluar la respiracion durante el dormir en ENMs

Correlacion sintomas diurnos es baja

Sedentarismo =fallo resp oculto

Alto nivel de sospecha necesario

Pistas

Cuando evaluar desorden de la respiracion en ENMs

Hypersomnolencia diurna, fallas cognitivas

dolor de cabeza al despertar,

sueño inquieto

Dormir no restorativo

Ahogos, apnea observada

observaciones de companero-a de cama:

ronquidos,

pesadillas, enuresis

No sx pero corpulmonale o eritrocitosis o Cifoscoliosis

Pistas fisiológicos: PImáx < 50% CV 1-1.5 CV acostado

Factores contribuyentes

Como evaluar

Optimo test para screening ?

Oximetria

Somnografia limitada

Polisomnografia (paradox) EtCo2 or transcutaneous = usamos

Presion intraesofagica raramente

CV erecto y acostado,

Pimax,

sniff test

Alteraciones del sueno en ENMs Somnolencia

Primaria/central o Secundaria = Mala calidad del dormir

Trastornos respiratorios nocturno precede fallo respiratorio diurno = alto nivel de sospecha

VNI beneficia QOL & sobrevivencia Todavia debatible ? Pero depende de la enfermedad Cuando evaluar con polisomnografia ? Cuando iniciar VNI nocturno? e Impacto psico-social

Hay amores que matan !

The end Gracias!

Neuromuscular diseases

Increase

UARaw

Micro

atelectasis

Decr V/Q

Hypoxemic

Hypercapneic

Respiratory

Failure

SLEEP

APNEA Obstructive

Centrals

SLEEP DISRUPTION

Reduced sleep time

Incr fragmentation

DAYTIME

HYPERSOMNOLENCE

FATIGUE

Decr VA

Respiratory

Muscle

Weakness

Decr CL

Central

Wake/sleep

Control

NIV

NONINVASIVE POSITIVE PRESSURE VENTILATION

NEUROMUSCULAR DISEASES

Improves Symptoms Sleep Daytime function Hypercapnia, Hypoxemia

Delays Functional deterioration Need for tracheostomy

Long term NIV in restrictive dis

Sx fatigue, am headache, EDS, nightmares, enuresis, dyspnea etc

Daytime PaCO2 > 45 or

Nocturnal desat=SpO2<90 for 5 min or >10% total monitoring time

NIF < 60 cm H2O or VC < 50%

Consensus CHEST 1999 116:521-534

Medicare: only respiratory muscle weakness or thoracic deformities.

How NIV helps in NMDs

Unloading inspiratory muscle Gigliotti etal Chest 91

Reduced inspiratory work Avoidance of resp muscle fatigue Reduced RR…Increased tidal vol

Improved gas exchange, V/Q microatelectasis, Hoeppner et al ARRD 84

Improved Central Chemoreceptor sensitivity to CO2 in chronic hypercapneics Elliot etal Thorax92

Decreased nocturnal arousals in SDB assoc w/ Chronic Respiratory Failure Elliot et al ARRD 87

Clues-progressive failure

Impaired cough effectiveness MEP < 40 cm H2O VC < 30% Max Cough Flow < 300 ml/l

Impaired sigh-atelectasis VC <20%

Impaired ventilation NIF < 20 VC < 10% HI CO2

Consider admission to ICU VC < 35mg/kg

Consider intubation and mechanical vent VC < 15mg/kg or dropping

rapidly

NonICU measure VC frequently VC > 35mg/Kg

Consider NIPPV for CRF

Disease specifics

Parkinson’s

Hypersomnolence Central

Insomnia

PLMNS

Fragmentation:tremor, stiffness, pain, depression

Drugs

REM Behaviour Disorder

Hallucinations-drug related

PARKINSONS

Respiratory Hypoventilation-rigidity

CSA-vent control

L-dopa respiratory dysfunction • Respiratory muscle rigity-akinesia

• Altered central ventilatory control

• Pleuro-pulmonary fibrosis (ergo derived dopa agonists)

Oromandibular dystonia

Upper airway dysfunction---OSA?

ALS

Median 3-5 y…30%alive in 5y10-20 10years

VC <50..SX <25% FAILURE

Awake ABG TOO late

Sniff test correlated w/ mortality better than VC but sensitivity hi 97 vs 58 but spec 79 vs 96

ALS

Sleep hypoventilation / hypoxemia

Frequent arousals

Decreased total sleep time

OSA in early disease (bulbar ALS)

Less OSA events with progression

Negative prognostic value: Diaphragmatic dysfunction

Severe REM sleep reduction

ALS………NIV

Improves quality of life

Prolongs life used >4hrs/d no bulbar

No data driven guidelines to initiate but……….(start “early” OK) Sleep SaO2 <88% > 5 min and Sxs

High PaCO2 awake or sleep ETCO2 rises

FVC <50%, Sniff<40cm,Pimax<60cm

Duchenne’s Muscular Dystrophy Recessive x-linked dystrophin deficiency

Respiratory muscle involvement inevitable

Sleep hypoventilation then daytime

Mostly OSA

Mostly Central Sleep apneas

Caution: “pseudo centrals” (less neg press)

Tonsillectomies ! In younger children

Muscular dystrophy

Inherited progressive myopathies mutations of distrophin gene

Guidelines Selfinflation in-exsuflator if VC <40%

Assisted cough techs VC<40% or 1.25L, peak cough flow<160 L/m or infection + PCF<270L/m

Nocturnal ventilation if Sx hypov VC<30% or SpO2<95% AHI >10/h, >4 episodes of SpO2 <92%, hypoxemia

Daytime vent inability to speak full sentence, abn deglution due to dyspena, CO2 etc

Postpolio syndrome

> 33% sleep disturbances

Hypoventilation

Apnea/hypopneas –obstructive/centrals

Sleep disruption

EDS

Caution: post anesthetics, sedatives

Myasthenia Gravis autoimmune postsynaptic –acetylcholine receptor ab

SDB is frequent even in the symptomatically well controlled

Mostly centrals in the past but

2006 prospective study nonREM OSA mostly

Risk factors : male sex, obesity, older age, corticosteroids

Peripheral Neuropathies e.g. Guillian-Barre, Charcot-Marie-Tooth, Diabetic etc)

Sleep fragmentation—pain =EDS

Bilateral phrenic neuropathies (GBS, CMT) Sleep fragmetation, Hypoventilation, hypoxemia, =EDS,

Reduced CSF hypocretin in GBS = EDS

Pharyngeal neuropathies =OSA (Charcot-Marie-Tooth)

SDB in Diabetic autonomic neuropathy Reduced chemoreceptor response to CO2

HISTORY- Congenital Kyphoscoliosis Accountant

8-1984 Age 45 FIO2 PaO2 PaCO2 FEV1 FVC

.5 41 82 .700 1020

10-1984 Tracheostomy 2. 82 49

+Home ventilator

7-1985 Return to work

tracheostomy pain

3-1987---BiPAP-- RA 67 53

1-1994 BiPAP 5.5 hrs RA 58 53 .600 .900

Working 4 hrs/ day 1 hr nap

2001 BiPAP at night O2 awake retired 5 yrs ago

El mecanismo del estado de vigilia funciona atraves del sistema de activacion reticular ascendente implica el tronco encefálico, proencefalo, talamo, hipotalamo que puede estar afectado en enf neurodegenerativas fig 1

Parkinsons degeneracion de neuronas dopaminergicas y colinergicas

English version

Chest sleep in america 2002

66% healthy adults vs 93% poor health Difficulty falling asleep

Walking up a lot or too early

Non restorative sleep

Snoring

unpleasant tingling in legs

pauses in breathing

Are nmd worse than healthy adults ?

NEUROMUSCULAR DISEASES 5

Onset of Respiratory failure is unpredictable Respiratory failure can be clinically occult due to sedentary existence Fatigue attributed to primary disorder Normal awake ABG does not exclude nocturnal hypoxemia/hypoventilation Noninvasive Nocturnal Ventilation is effective. When to start?

NEUROMUSCULAR DISEASES

Severe Kyphoscoliosis Post polio syndrome Amyotrophic Lateral Sclerosis Muscular Dystrophy Quadriplegia Acid Maltase Deficiency Idiopathic diaphragmatic weakness

Sleep related dysfunction in nmd

Proven: Poor sleep quality……33-96%……….why? SDB precedes diurnal resp failure why NIV benefits QOL & survival Still debatable Timing for NPSG or ? clues When to initiate NIV

Repeat at end

Healthy Sleep vs Wakefulness

Ventilation in all sleep stages

NREM marginal Metabolic Rate 7%

Ventilatory drives O2 / CO2 (men)

Upper Airways Resistance (load compensation)

REM 40% lower ventilation ! Decreased Central Respiratory Output

DEMAND VS RESPONSE

Healthy person

Neuro-muscular Diseases

Increased Demand ?

Increased Work of Breathing upper airway resistance (resistive load)

• Pharyngo-laryngo dysfunction

compliance chest wall and/or lungs • Micro-atelectasis

• Fibrosis……aspiration?

• Rib cage stiffness: ankylosis, intercostal spasticity or paralysis

• Obesity

Additional factors in N MD

Muscle weakness (but fatigue unusual)

Rate of progression

Distribution

Impaired response to demand/stimuli (e.g. resistance or chemical)

Impaired chemosensitivity

Restrictive lung disease

Altered central control of sleep…….

expand

Factores adicionales en ENMs

Debilidad muscular (pero fatiga inusual) expand

tasa de progresión

distribución

Reducida respuesta a la demanda / estímulos (e.g. resistencia o químicas)

Alteración chemosensitivity

Enfermedad pulmonar restrictiva

Alterado control central del sueno…….

Reduced Response

Muscle weakness (but fatigue unusual)

Rate of progression

Distribution

Impaired response to demand/stimuli (e.g. resistance or chemical)

Impaired chemosensitivity O2-CO2

Altered central control of sleep…….

Impact of sleep in nmd ?????

Chest/lung compliance + Muscle weakness

Upper airway resistance + chemosensitivity

load compensation

central drive

Diaphragm burden (REM intercostal/accessory hypotonia)

Ventilation

PaCO2 PaO2

How to and when to assess for SDB in NMDs

EDS, am headache, restless sleep

Nonrestorative sleep

Chocking at night

Bedpartner observations: snoring, apneas

Nightmares , enuresis

No sx but corpulmonale or erithocytosis or lo VC

Kyphoscoliosis

Physiological clues: Pimax <50% VC 1-1.5L

Contributing factors

What test to use

Optimal test for screening nmds has not been established

Oximetry

Limited study

Polysomnography (paradox)

EtCo2 we use

Esoph press

VC, Pimax, sniff test

Myotonic dystrophy (multisystem !) (autosomal dominant)

Daytime sleepiness & fatigue 80% !!

SDB 16-75% or

Altered Central sleep regulation

Abnormal sleep architecture: Sleep onset REM

Reduced CSF hypocretin 1 levels

No correlation severity to CTG repeats

Myotonic dystrophy type I

Italian study sleep disordered breathing 22/40 OSA,

5/40 periodic breathing

4/40 hypoventilation,

No correlation clinico-neuro features

Conclusion :Do polysomnography periodically

Expansion of CTG repeat in the DMPK gene

Other myopathies non-DMD, congenital, metabolic myopathies

Hypoventilation 52% in congenital myopathies

Acid-maltase deficiency hi % SDB due to disproportionate resp musle involvement

Risk factors---predispose to SDB to discuss when who to study?

Longer REM sleep Diaphragmatic weakness-Supine position Increased upper airway resistance

Bulbar involvement: pharyngeal hypotonia, retrgnacia, macroglosia, craniofacial dysmorphia URI-tonsils

Restrictive lung function Obesity (DMD & MG Rx w/ pred) Kyphoscoliosis

CNS involvement Impaired respiratory chemo sensitivity

Diabetic neuropathies Chronic hypercapnia Myopathies

Trastornos del sueño en Enfermedades Neuro-Musculares ENMs

Guillermo do Pico MD FCCP

Professor Emeritus

University of Wisconsin

Mientras dormimos somos todos iguales Proberbio espanol

RESPIRATORY MUSCLES

“

The end

Gracias !

Hypocretin …..

Activity respiratory muscles during sleep……

Intercostal and

accessory muscle

Diaphragm

Cerebral blood flow +/-

NonREM REM

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