Topic 6.2. Breathing related sleep disturbance and nocturnal hypoventilation

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This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.

Topic Contents

6.2 Breathing related sleep disturbance and nocturnal hypoventilation
6.2.1 The effects of Friedreich ataxia on sleep disordered breathing
6.2.2 Monitoring sleep disordered breathing
6.2.3 Management of sleep disordered breathing

Disclaimer / Intended Use / Funding

Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.

These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.

Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.

The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.

Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.

These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.

Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.


6.2 Breathing related sleep disturbance and nocturnal hypoventilation

Sub Subramony, Barbara Smith, Katherine Mathews and Louise Corben

6.2.1 The effects of Friedreich ataxia on sleep disordered breathing

Sleep disordered breathing (SDB) has not been extensively documented in Friedreich ataxia (FRDA). There is a single case report documenting a patient with severe FRDA and “arduous” breathing and oxygen desaturation, together with SDB at night (9). Manni et al (10) reported polysomnography on nine persons with various hereditary ataxias and reported SDB in three people with FRDA. In a study from Australia, Corben et al (11) administered the Epworth Sleepiness Scale to 82 individuals with FRDA and found abnormal values in 21. Polysomnography in these selected individuals documented obstructive sleep apnea (OSA) in 17 of the 21. The risk of OSA in FRDA was estimated to be over 5 times that in the general population. In a web-based survey of FRDA individuals in the FARA registry (12), 16.4% reported a diagnosis of sleep apnea. Sleep apnea is associated with older age and/or longer duration of disease (11, 12).

SDB in neuromuscular disorders such as FRDA can result from different problems. Reduced muscle tone in the upper airway leads to OSA. Reduced respiratory muscle strength leading to reduced respiratory volumes and lessening chest wall compliance causing atelectasis and subsequent ventilation-perfusion mismatch can lead to nocturnal hypoventilation, even without sleep apnea, though this was not seen in the study from Australia (11). Both sleep apnea and nocturnal hypoventilation can lead to daytime symptoms that include excessive sleepiness, fatigue, poor concentration, morning headache, dyspnea and orthopnea.

6.2.2 Monitoring sleep disordered breathing

Monitoring for SDB should be done at least annually in individuals with FRDA with advanced disease (i.e., non-ambulatory; or earlier if symptoms of SDB are elicited) during clinic visits.

Monitoring at clinic visits should include:

● Administer a neuro-respiratory checklist including questions about orthopnea, dyspnea during ordinary daytime activities, apnea during the night, poor sleep quality during the night, morning headache, decreased attention and concentration during the daytime, excess daytime sleepiness, excessive fatigue and repeated chest infections (5)

● Administer a sleepiness questionnaire (e.g., Epworth sleepiness scale) and a fatigue scale

● Assess respiratory excursions and cough strength during physical examination

● Perform pulmonary function tests (PFT) to include forced vital capacity, maximal inspiratory and expiratory pressures and peak expiratory cough flow

● Polysomnography with capnography if obstructive sleep apnea or nocturnal hypoventilation is suspected based on above clinic based assessments.

6.2.3 Management of sleep disordered breathing

● SDB primarily diagnosed as OSA can be managed with continuous positive airway pressure (CPAP) at night

● While CPAP is the primary treatment of OSA, alternative therapies may be used in certain situations. For a clear nasopharyngeal obstruction, nasal steroids or removal of obstruction may be indicated. Individuals with mild OSA may be prescribed a customized oral appliance to support the position of the mandible and promote airway patency during sleep.

● Nocturnal hypoventilation is managed by non-invasive ventilation using bi-level positive airway pressure (biPAP) or average volume assured pressure support (AVAPS) (see section 6.1: Management of reduced pulmonary function)

● General health measures, such as maintaining ideal weight, sleep hygiene and avoidance of alcohol, should be recommended

To inform clinical practice, more data are needed on the prevalence of SDB in FRDA, the risk factors associated with it and the effects of interventions on symptom reduction, quality of life and on progression of cardiac and neurological manifestations of FRDA

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Please note: Recommendations are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group. Best Practice Statements are commonly accepted practices, as such formal rating of the quality of evidence by the GRADE process is not indicated. In addition if recommendations from the 2014 guidelines were deemed still relevant, although unable to undergo the scrutiny from a GRADE framework, they were also included as best practice statements.
Monitoring

QUESTION: Should monitoring for restrictive lung disease/sleep disordered breathing/sleep apnea versus no monitoring be used for people with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION:
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯

RECOMMENDATION: We conditionally recommend that individuals with advanced Friedreich ataxia be monitored* at least annually for restrictive lung disease and sleep disordered breathing (SDB).
*Monitoring should include a respiratory symptom check list (dyspnea, orthopnea, episodes of apnea during night, poor sleep, morning headache, decreased concentration and attention, fatigue, treated chest infection within the past few months), a sleepiness questionnaire and a fatigue scale. Annual (or more frequent) pulmonary function testing should be performed to include forced vital capacity (FVC), maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), peak expiratory cough flow (PECF), SpO2 and partial pressure of end tidal CO2 (PetCO2).

JUSTIFICATION:There are no published data. Expert opinion and limited unpublished data suggest that restrictive lung disease and SDB can occur in advanced Friedreich ataxia. Monitoring will be of benefit. Methods for monitoring include using a respiratory symptom check list (5), sleepiness and fatigue scales and pulmonary function tests.

Restrictive lung disease and SDB can lead to abnormal blood gases and symptoms that impair quality of life. Detecting these and providing appropriate intervention will be of benefit.

SUBGROUP CONSIDERATION: Monitoring is recommended for individuals with Friedreich ataxia with advanced disease.

Evidence to Recommendation Table PDF
Monitoring at diagnosis

QUESTION: Should monitoring for restrictive lung disease/sleep disordered breathing/sleep apnea at diagnosis versus monitoring at later stages be used for people with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION:
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯

RECOMMENDATION: We conditionally recommend against monitoring for restrictive lung disease and sleep disordered breathing at diagnosis of Friedreich ataxia rather than at later stages of the disease, as there is no evidence that this would be of benefit.

JUSTIFICATION: There are no published data on prevalence of abnormal respiratory muscle function in Friedreich ataxia. Unpublished data indicates that restrictive lung disease and impaired cough can occur in later stages of the disease. There is no clear evidence of the effect of monitoring for restrictive lung disease/SDB/sleep apnea at diagnosis compared to later in the disease, on abnormal lung volumes; impaired airway clearance; excessive daytime sleepiness, or fatigue in individuals with Friedreich ataxia. Monitoring could be done in later stages of Friedreich ataxia.

SUBGROUP CONSIDERATION: Individuals who are later in the progression of Friedreich ataxia are more likely to experience restrictive lung disease.

Evidence to Recommendation Table PDF
Non-invasive ventilation

QUESTION: Should non-invasive ventilation versus no intervention be used for sleep disordered breathing (SDB)/sleep apnea and nocturnal hypoventilation in Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION:
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯

RECOMMENDATION: In individuals with Friedreich ataxia and sleep disordered breathing/sleep apnea and/or evidence of nocturnal hypoventilation, we suggest non-invasive ventilation be implemented to assist in fatigue; sleepiness; quality of night time sleep; blood gas parameters; and cardiac function.

JUSTIFICATION: Sleep apnea and nocturnal hypoventilation related to obstructive sleep apnea or restrictive lung disease cause abnormal blood gases and lead to symptoms with deleterious consequences. There are no published data in Friedreich ataxia on the use of non-invasive ventilation (NIV). Also, there are no recent publications on this in other neuromuscular disorders. A Cochrane review from 2014 (13) found low level evidence in favor of NIV for reducing mortality, reducing unexpected hospitalizations, and reducing symptoms of SDB and hypoventilation in other neuromuscular disorders (mostly ALS and DMD). Care recommendation guidelines in similar disorders include nocturnal assisted ventilation for SDB, sleep related hypoventilation and abnormal pulmonary function tests.

SUBGROUP CONSIDERATION: This recommendation is for individuals with advanced Friedreich ataxia with documented sleep disordered breathing including nocturnal hypoventilation and/or abnormal pulmonary function tests.

Evidence to Recommendation Table PDF
Please note: Recommendations are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group. Best Practice Statements are commonly accepted practices, as such formal rating of the quality of evidence by the GRADE process is not indicated. In addition if recommendations from the 2014 guidelines were deemed still relevant, although unable to undergo the scrutiny from a GRADE framework, they were also included as best practice statements.
Individuals with advanced Friedreich ataxia should be monitored for sleep disordered breathing using clinical questionnaires and assessments. When obstructive sleep apnea is diagnosed, appropriate night-time ventilatory assistance or an appropriate alternative treatment should be offered.

Lay summary of clinical recommendations for breathing related sleep disturbance & nocturnal hypoventilation in Friedreich ataxia


Why these recommendations?
Limited research shows that sleep disruption due to sleep disordered breathing (SDB) happens in individuals with Friedreich ataxia, particularly those who are in the later stages of the disease. Experience from other neuromuscular disorders suggests that SDB can be related to problems with the muscles that control breathing and throat and upper airway muscles, as well as stiffening of the chest muscles and lungs. Sleep disruption can also be unrelated to breathing problems (such as disruption due to restless legs).

Disrupted sleep related to SDB includes sleep apnea (short periods when breathing stops during sleep), often from throat muscles closing off (obstructive sleep apnea), and nocturnal hypoventilation, where there is not enough movement of air into the lungs during sleep. Nocturnal hypoventilation results from weak respiratory muscles and can lead to high carbon dioxide and low oxygen levels in the blood. In other diseases, this often happens in those with shallow breath volumes, since the depth of breathing falls further during sleep. Sleep apnea and nocturnal hypoventilation must be considered in individuals with poor sleep quality and daytime fatigue and sleepiness, or in those with shallow breathing.

Monitoring for sleep disorders in individuals with Friedreich ataxia includes:
● asking about daytime sleepiness or fatigue, headache in the morning, snoring or shortness of breath
● a sleep study (polysomnography) for those reporting a history of snoring and poor sleep quality.
● Individuals who are no longer ambulatory are at increased risk for nocturnal hypoventilation and sleep apnea; it is recommended they undergo appropriate lung function tests at least yearly or if they experience concerning symptoms.
● Other tests might include measuring oxygen levels using a “pulse oximeter” attached to the finger, and carbon dioxide levels in air being expelled, usually done by placing a cannula in the nostrils. Tests of oxygen and carbon dioxide levels in the blood can provide an indication of hypoventilation, as can a sleep study.

Treatments for sleep disordered breathing are generally targeted at the underlying problem:
● If the problem is failure to maintain an open airway at the level of the throat, continuous positive airway pressure (CPAP) provided through a mask can be helpful.
● If the problem is nocturnal hypoventilation, then treatment is focused on increasing the volume of the breaths taken in sleep using bilevel positive airway pressure (biPAP; provides supported breaths) or average volume assured pressure support (AVAPS) during sleep.
● There are other interventions that target anatomical obstructions in selected individuals with obstructive sleep apnea.

What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
It may be important for you to discuss possible problems with sleep with your care providers and encourage good communication between members of your care team, including your neurologist, pulmonary or sleep specialist, physical therapist and primary care physician.

Who are these recommendations specifically for?
These recommendations are relevant for individuals with advanced Friedreich ataxia and those with documented sleep apnea or nocturnal hypoventilation.

Louise Corben, PhD
Principal Research Fellow, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Email: louise.corben@mcri.edu.au

Katherine Mathews, MD
Professor, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Email: katherine-mathews@uiowa.edu

Barbara Smith, PhD, PT
Assistant Professor, University of Florida, Gainesville, Florida, USA

Sub H. Subramony, MD
Professor of Neurology and Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA
Email: s.subramony@neurology.ufl.edu

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These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.

This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.

It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.