Post on 21-Feb-2020
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
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
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
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
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
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
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