Neuromuscular Disorders in Sleep

Luisa Bazan, MD

Henry Ford Sleep Disorders and Research Center

Henry Ford Health System

Conflict of Interest Disclosures for Speakers

1. I do not have any relationships with any entities producing, marketing, re-selling, or

distributing health care goods or services consumed by, or used on, patients, OR

2. I have the following relationships with entities producing, marketing, re-selling, or

distributing health care goods or services consumed by, or used on, patients:

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Grant/Research Support

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Speakers’ Bureaus

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3. The material presented in this lecture has no relationship with any of these potential conflicts, OR

4. This talk presents material that is related to one or more of these potential conflicts, and the following

objective references are provided as support for this lecture:

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Objectives

• Sleep-wake disturbances in patients with neuromuscular (NM) disease

• Sleep disorder breathing in NM disease – Pathophysiology

• Timing of NIPPV

• Benefits of NIPPV

• Role of Polysomnography

• Home Management

Sleep-wake disturbances in NM disease

• Periodic limb movements of sleep (PLMs) has been uncovered in patients with NM and spinal cord disorders via PSG

• Central hypersomnia (Myotonic dystrophy)

• Painful polyneuropathies and muscle pain in the setting of immobility often experience insomnia, sleep fragmentation, EDS, and symptoms of RLS

• Insufficient sleep can results in morning headaches, mood problems and impaired cognition

• Sleep disorder breathing • Sleep disturbances in NM diseases often caused by sleep-related ventilator

dysfunction • Damage to the anterior horn cell, motor root, peripheral nerve, NM junction

or the muscle fiber can result in thoracic, diaphragmatic, or oropharyngeal muscle weakness resulting in sleep dysfunction

• 33.1% of DM1 patients had EDS compared to 7.9% of controls

• Daytime sleepiness severity was related to the degree of muscular impairment

• 43 (29 women, mean age 49.7 yo) DM1 subjects agreed to undergo: • PSG for two consecutive nights with MSLT

• Questionnaires: sleep diary, ESS, respiratory function and narcolepsy symptoms

• 21/43 (50%) were found to have ESS ≥ 11

• 19/43 (44.2%) were found to have MSLT ≤ 8 min

• 30/43 (69.8%) were found to have either of the above

• 100 patients vs 100 controls matched for age and sex

• Night time complaints was collected using Pittsburg Sleep Quality Index (PSQI), and ESS

• Functional disability was assessed using the ALS Functional Ratin Scale-Revised (ALSFRS-R)

• Overnight PSG was done in 12 patients

Sleep Disorder Breathing in NMD

• SDB are common in NMD with a prevalence of 40%

• The prevalence increases as the disorder progresses

• NMDs shared common features which lead to various respiratory disorders during sleep:

• Diaphragmatic weakness

• Anatomic or neurologic propensity to OSA

• Potential cardiomyopathy

Sleep-Related Alveolar Hypercapnic Hypoventilation • Most common form of chronic SDB in patients with NMD

(neuromuscular disorders)

• Typically first develops during REM sleep

• NMD patient with significant diaphragmatic weakness depend on their intercostal and accessory muscles to breathe

Pathophysiology

• Restrictive lung disease • Decrease vital capacity (VC)

• Sitting-to-supine changes in VC > 25%

• Reduction in compliance can be present even in the absence of spinal deformities and is likely related to increased stiffness of the rib cage from a chronic reduction in its expansion range

Physiologic Respiratory Vulnerabilities during sleep

• Interactions between sleep and lung volumes • Sleep compounds the reduction in lung volumes imposed by NMD and the supine

position by reducing the functional residual capacity (FRC) by 6 to 15%

• Low lung volumes reduce the stability of the upper airway facilitating SDB events

• Reduction of TV by approximately 10% in N2 sleep contributes to the risk of hypoventilation

• Loss of muscle tone in REM sleep • Reduction on in the contribution of the intercostal muscles may reduce the tidal

volume and produce nocturnal hypoventilation

• Reduced chemosensitivity to hypercapnia and hypoxia, worse during REM sleep

• Reduced activity of pharyngeal dilators • Due to a decrease in the wakefulness drive to breathe

• Inspiratory laryngeal and expiratory pharyngeal nerves are suppressed during REM

Triggers for evaluation

• SOB bending over, lying supine or sleeping

• Sleep complaints: frequent nocturnal awakenings (>3/night), restlessness, vivid dreams, poor concentration, mood disturbance, sweating or difficulty awakening

• Headache upon awakening

• Daytime sleepiness, tiredness or generalized fatigue

• Apnea, gasps, snorts, tachypnea or cyanosis when sleeping

• Coughing during/after eating/drinking; problems with speech, swallowing, recurrent aspiration, frequent lower respiratory infections, weak cough, and reduced clearance of secretions

Criteria to initiate NIV

• Forced vital capacity less than 50% (predicted)

• Maximal inspiratory pressure greater than -60 cmH2O

• PaCO2 ≥ 45 mmHg

• Sleep oximetry demonstrates oxygen saturation ≤ 88% for at least 5 minutes

Potential benefits of NIPPV

• Survival: • Improves survival in rapidly progressive NMD such as ALS as well as more

slowly progressive disorders such as Duchenne muscular dystrophy

• Quality of sleep: • Improves subjective sleep quality and PSG measures in diverse NMD

• 39 ALS patients were treated with NIV

• Reason for treatment: orthopnea, new hypercapnia, or both

• Two groups: tolerant vs intolerant

• RR of death for intolerant patients was 3.1 times higher than tolerant patients

• Bulbar symptoms were more prevalent among intolerant patients

• 50 stable NM patients under long-term NIV were administered PSQI and underwent PSG

• ABG, FVC and respiratory muscular strength were measured

• 33/50 classified as poor sleepers with PSQI ≥ 5

• Only base excess (BE) and %N3 independently predicted global PSQI

• Conclusions: • Subjective sleep quality is often poor in NM patients under long-term NIV

• %N3 sleep and chronic hypoventilation resulting in increased BE are independent predictors of subjective sleep quality

• Since inadequate NIV setting or application can influence sleep structure and alveolar ventilation, great care should be paid to the setting and the correct application of NIV to ensure a better subjective sleep quality

• 24 ALS patients underwent 4 nights PSG in-hospital NIV titration with nocturnal capnography and readmitted after one month

• Questionnaires were used to assess QOL

• Results: • In the total group, N3 and REM sleep increased and arousals index improved • Nocturnal oxygen and CO2 levels improved in the total and non-bulbar group • Bulbar patients did not show improvement in respiratory function or sleep

structure

• Conclusions: • There is improvement of sleep architecture, CO2 and nocturnal O2 sat at the

end of NIV titration and after one month of NIV in ALS patients • More studies are needed to identify the appropriate time to start NIV in

bulbar patients • Accurate titration of NIV by PSG improves sleep quality

JCSM 2015;11(5):559-566

Role of Polysomnography

• American Academy of Sleep Medicine: • Diagnostic perspective:

• “for patients with neuromuscular disorders and sleep related symptoms, polysomnography is routinely indicated to evaluate symptoms of sleep disorders that are not adequately diagnosed by obtaining a sleep history, assessing sleep hygiene, and reviewing sleep diaries”

• Therapeutic perspective: • Best clinic practice report: “noninvasive positive pressure titration with attended

polysomnography is recommended method to determine an effective level of nocturnal ventilator support in patients with chronic alveolar hypoventilation” and “allows definitive identification of an adequate level of ventilator support for patients with neuromuscular disease in whom noninvasive positive pressure ventilation treatment is planned”

Role of Polysomnography

• Polysomnography plays a central role for the following: • The correct classification of respiratory events,

• The identification of events that may be triggered by noninvasive ventilation

• The implementation of an effective titration strategy

Goals of NIPPV titration for NM patients

• Different than for OSA patients

• Study is successful when: • RR is not too low, with a backup rate sufficient to eliminate central apnea

events

• Vt that is adequate so that oxygen saturation and carbon dioxide levels are within normal range

• The use of supplemental oxygen should not be necessary, oxygen supplementation should be the last resort

PSG Challenges on NMD Patients

• In clinical practice majority of patients are set empirically due to the following:

• Limitations concerning subject mobility: • Wheelchair accessibility

• Lifts or other transfer apparatus

• Adaptive call lights

• Space for caregivers

• Suction pumps

• Others

• Laboratory availability and capability (including availability of dedicated hypoventilation protocols rather than OSA protocols) and;

• Reimbursement

Empiric set up of NIPPV:

• Based on patient comfort

• Partly informed by other considerations: • BMI (heavier subjects may require a greater pressure support),

• Ideal body weight (particularly for self-adjusting devices),

• Previous information (known OSA or obstructive lung disease may require higher expiratory pressure settings or pressure support)

Type of Devices

• Options: • Volume controlled – less well tolerated

• GI side effects more common with this mode • Pressure controlled – most common (pressure support,

pressure control, bilevel positive airway pressure, volume-assured support)

Volume-assured pressure support (AVAPS,IVAPS)

• Target a preset minute ventilation or alveolar ventilation

• Comparable control of oxygenation and sleep quality in stable hypercapnic disorders, including NMD

• Advantages: • Automatic adjustments with disease progression and

improved adherence

• Disadvantages: • Associated with asynchronous events and increased

arousals

• Goal: to determine whether AutoEPAP was noninferior to FixedEPAP for the control of OSA during IVAPS treatment of chronic hypoventilation

• Randomized, double-blind, crossover study

• 25 adults (14 male) with chronic hypoventilation secondary to OHS (11), COPD (9) or NMD (5) on established home NIV therapy were included

• Average age 57 and on NIV for 3 months or more and AHI > 5/hour

• AutoEPAP was noninferior to Fixed EPAP for the control of OSA (AHI 2.7 vs 2.4)

• Both were equivalent in PSG sleep breathing and sleep quality, self reported sleep quality, device comfort, and patient preference

• Mean EPAP with the auto and fixed modes was 10.8 +/- 2 vs 11.8 +/- 3,9, no significantly different

Results

Home management of NIPPV

• Nocturnal oximetry every 3 months has shown in ALS patients improved outcomes if normal

• Normal was defined as less than 5% of nocturnal monitoring period with a saturation less than 90%

• Survival at 1 year in those with normal pulse oximetry was 75% as compared with 57% for those who did not maintain adequate saturation

Amyotroph Lateral Scler Frontotemporal Degener. 2013 Sep;14(5-6):373-9

Conclusions

• Sleep disturbances in NMD are secondary to weakness in respiratory and oropharyngeal muscles, phrenic and intercostal neuropathy and NM junction dysfunction, and abnormalities in the central respiratory drive

• Central hypersomnias have been described (myotonic dystrophy, and GBS)

• SDB is the most common sleep disorder

• PSG can identify and quantify SDB, nocturnal hypoventilation, and hypoxemia, and can uncover other sleep alterations. MSLT might be indicated in certain cases

• Treatment of sleep disorders can improve QOL

• NIPPV improves QOL and mortality in NMD such as ALS

• High index of suspicion for potential sleep disorders is needed in patients with NMD because these are treatable complications in an otherwise progressive disease process

• More studies are required to determine what NMD patients will benefit from PSG vs empiric titration based on the advances in technology

Thank you

• Questions