Respiratory function in neuromuscular disorders

This Update looks at the different ways respiratory failure can be managed in children with neuromuscular disorders. It is by Professor Dominic Fitzgerald, MBBS, PhD, FRACP.

Professor Dominic Fitzgerald, MBBS, PhD, FRACP
Paediatric respiratory and sleep physician at the Children’s Hospital at Westmead, NSW.

INTRODUCTION
THE diagnosis of neuromuscular weakness can be challenging for clinicians, and one that involves a detailed physical examination and specialist investigations.

There can be a heterogeneous phenotype for some conditions, but some of the more common ones, like Duchenne muscular dystrophy (DMD), can be suspected on screening tests, such as a markedly  (tenfold) elevated serum creatine kinase. Definitive diagnoses can now be provided by gene testing, which has moved from the research domain firmly into the clinical domain in the past decade.

Once the diagnosis is made, there are common problems with respiratory function that need acute intervention, as well as others that need longitudinal monitoring.

Importantly, issues of respiratory wellbeing may be very relevant in infants and young children. These include acute episodes of respiratory failure (e.g. bronchiolitis and pneumonia), pulmonary function testing for the progression of restrictive lung disease, scoliosis and nocturnal hypoventilation, which precedes awake respiratory failure.

DIAGNOSING THE NEUROMUSCULAR CONDITION
Some children will present with respiratory failure in infancy due to an underlying neuromuscular condition. Myotonic dystrophy or spinal muscular atrophy are examples of this.

The key to defining the type of weakness that a child has begins with a thorough history.

This starts with the pregnancy and birth. Are the parents consanguineous or is there a family history of neuromuscular disorders? How many people in the family are affected? During the pregnancy, were there decreased fetal movements suggesting weakness? Was polyhydramnios present, suggesting decreased swallowing of amniotic fluid, which is seen in some myopathies? Was the baby delivered from a breech position? Was there a history of congenital hip dysplasia or joint contractures?

The newborn may have respiratory difficulties that are apparent soon after birth, or poor feeding necessitating nasogastric feeds, and a floppy ‘frog-like’ position noted when lying supine.

The lesion may be located from the motor cortex to the muscle fibre and anywhere in between. This incorporates problems with myelination and structural abnormalities of the central nervous system (including the brain stem and spinal cord), space-occupying lesions, anterior horn cell lesions, peripheral nerves, neuromuscular junction and muscle fibres themselves.

Upper motor neuron lesions will manifest with hypertonia, hyper-reflexia, clonus of the ankle joints (typically) and an up-going toe on stimulation of the sole of the foot (positive Babinski sign).

In contrast, lower motor neuron lesions will present with reduced or absent reflexes and hypotonia.

An objective test of muscle weakness is the Gowers sign, in which the child is asked to lie on their back and then stand up. If present, the child will roll on to their stomach, push themselves up onto all fours and ‘climb up’ their thighs to stand upright.

A useful clinical sign to elicit is that of tongue fasciculations, described as the tongue looking like ‘a bag of worms’, which is seen in spinal muscular atrophy and other anterior horn cell lesions.

WHICH CHILDREN ARE AT RISK OF RESPIRATORY FAILURE?
Whatever the cause of moderate to severe neuromuscular weakness, there remains the common pathway of impaired clearance of mucus, recurrent chest infections and respiratory failure.

Part of the routine assessment of any child with neuromuscular weakness involves consideration of respiratory compromise. This may be contributed to by many factors, including impaired swallowing and pulmonary aspiration of food or saliva, intercurrent infections (e.g. bronchiolitis in a baby), impaired cough and clearance of airway secretions, poor lung expansion with restrictive lung disease and scoliosis, pulmonary atelectasis, cardiac failure from a cardiomyopathy or arrhythmia, and sleep-disordered breathing.

Any child’s nutritional state is a reasonable proxy for health and wellbeing. How a child with neuromuscular weakness feeds is important.

Progressive conditions such as DMD will inevitably be associated with difficulty swallowing, which is suggested by coughing and choking when feeding or an increasing frequency of chest infections.

A child who has progressed to gastrostomy feeding may have episodes of vomiting and reflux of intragastric feeds with intercurrent upper respiratory tract infections.

Any child with reduced lung function will have reduced lung volumes and therefore reduced pulmonary reserve to deal with increased mucus production with respiratory infections; they may rapidly deteriorate with the inability to clear airway secretions. This is exacerbated by a weak cough, the body’s best defence against chest infections.

These children will need assistance to clear airway secretions, which will come from physiotherapy techniques such as huffing, positive expiratory pressure masks, nebulised hypertonic saline and cough-assist devices. Some of these techniques and treatments have been used with good effect in children with more significant neurocognitive problems such as cerebral palsy.

CHEST PHYSIOTHERAPY TECHNIQUES
The goal of chest physiotherapy is to help the child clear mucus from their chest. This is facilitated by a deep breath, which opens the airway, loosens secretions and allows air to pass around mucus. When the child coughs and exhales from a high lung volume, they can force the secretions proximally and expel them from the airways.

Often the physiotherapy is preceded by inhaling medications to humidify or irritate the airways. One such method has been the use of nebulised hypertonic saline, which has been shown to be efficacious in clearing secretions in suppurative lung diseases such as cystic fibrosis.

In young children, the standard approach involves postural drainage and the manual techniques of percussion and vibrations. Chest wall percussion involves ‘chest clapping’ using the hand and may require the use of oral or nasopharyngeal suctioning. As the chest wall is highly compliant in young children, careful training is given to parents so as not to apply too much force.

The common purpose of augmenting cough can involve techniques to increase the inspiratory lung volume above that of a normal breath (spontaneous vital capacity). A patient takes a breath in and, if able, holds the breath with the glottis closed; another breath is then taken to further increase the lung volume. This may be possible if the child has the understanding and strength to do this, but it can also be facilitated using a bag-valve-mask system, a portable ventilator (bi-level non-invasive machine with a mask) or ‘frog breathing’, also known as glossopharyngeal breathing.

A manually assisted cough may also be useful where the chest wall or abdomen are compressed. If the abdomen is compressed when the patient coughs, the sudden increase in abdominal pressure will elevate the diaphragm, which will raise intrathoracic pressure and increase expiratory airflow.

In addition, there are ‘cough assist’ devices that can apply a positive pressure to the airway (‘insufflation’) and then rapidly shift to a negative pressure (‘exsufflation’), which results in a high expiratory flow rate, stimulating a natural cough.

MONITORING RESPIRATORY FUNCTION
There are no clinical findings, other than the presence of scoliosis, which accurately predict respiratory outcome for children with neuromuscular weakness. This emphasises the need to undertake regular monitoring of respiratory function and sleep breathing.

The goal, of course, is to optimise patient-important quality-of-life measures such as wakefulness, concentration, mood and participation in school and activities.

Nonetheless, our ability to improve patient-important outcomes rests upon engaging with the children and their families, encouraging compliance with treatments, and using medically objective measures such as vital capacity, tests of respiratory muscle strength, oximetry and measures of sleep-disordered breathing as part of important background information for assessing declining muscle strength and respiratory function.

Spirometry is readily undertaken and should be done on a twice-yearly basis. The vital capacity is a useful predictor of susceptibility to chest infections, the need for non-invasive respiratory support and survival for conditions such as DMD.

Additional tests are also undertaken to measure respiratory muscle strength (maximal inspiratory pressure, sniff nasal inspiratory pressure and maximal expiratory pressure), but, in reality, these tests offer little additional information than can be derived from the vital capacity.

Consequently, measurement of vital capacity should be undertaken unless cognitively the child is not capable of performing it.

SCOLIOSIS
The presence of scoliosis and its progression reflects the severity of the underlying neuromuscular weakness. It is universal in more severe cases of SMA types I and II, very common in DMD (70–90%), and uncommon in the milder Becker’s muscular dystrophy.

Scoliosis is associated with a lower pulmonary vital capacity (lung volume for gas exchange), a distorted centre of gravity, altered posture and discomfort.

The observation of scoliosis should prompt consideration of its effect on lung function. The earlier the appearance of scoliosis, especially in infancy and the preschool years, the more likely it will be associated with ipsilateral pulmonary hypoplasia.

If scoliosis does not appear until middle childhood and early adolescence, the likelihood is that the lungs have grown to a reasonable size and so pulmonary hypoplasia is less likely.

The progression of scoliosis during the teenage years is the most likely course, and this results from accelerated growth of the skeleton during adolescence, progression of the underlying neuromuscular weakness and more time in the seated position, which follows the loss of ambulation (typically in DMD).

The longer the standing position can be maintained, even for several hours per day, the better in terms of delaying the progression of the scoliosis.

Indeed, the use of systemic corticosteroids for the treatment of DMD has delayed the onset of boys becoming wheelchair-bound.

MANAGEMENT
The initial management of scoliosis is regular observation, followed in
some cases by the fitting of a brace to improve the rigidity of the thorax and posture.

Braces are uncomfortable, not well tolerated for lengthy periods of time (they need to be worn for about 23 hours daily) and are unable to be fitted to obese boys with DMD.

Bracing may slow the progress of scoliosis but does not affect its final severity.

The decision to operate on a child with progressive scoliosis is a clinical one supported by measurements of the degree of scoliosis (Cobb angle) derived from measurements undertaken on spinal radiographs.

Scoliosis surgery improves sitting comfort, appearance and quality of life.

It does not allow the patient to regain lost vital capacity (lung volume).

In order to achieve maximum vertical (thoracic) growth, surgery is optimally delayed beyond the age of 10 years.

By this age, 80% of thoracic height has been achieved, but only 50% of adult thoracic volume.

SLEEP-BREATHING ISSUES IN NEUROMUSCULAR WEAKNESS
The measurement of an arterial blood gas is a routine test in adults at risk of respiratory failure. This is less often undertaken in children, and thus either a capillary gas or a free-flowing venous gas may be used.

The presence of an elevated carbon dioxide level on a sample taken from an awake patient indicates respiratory failure. This means respiratory failure will be more marked during sleep.

However, there are considerable limitations with sampling for these measures in children (crying, screaming and lack of cooperation), which may lead one to sometimes question the validity of the result.

With the progression of neuromuscular weakness, hypoventilation in sleep will occur and manifest with periods of hypoxaemia and subsequently with hypercarbia. Hypoventilation begins in REM sleep when intercostals, upper airway and accessory muscle strength are most compromised, and then becomes apparent in all sleep stages.

The gold standard for assessing sleep breathing is the overnight polysomnogram, but there may be limited access to the studies. Consequently, other measures are used.

Overnight continuous oximetry will not reliably distinguish between obstructive sleep apnoea (where snoring is a predominant feature) and hypoventilation, but it is useful to inform the clinician of the presence of nocturnal hypoxia, which requires further assessment.

In general terms, indications for an overnight polysomnogram include the presence of a vital capacity lower than 60% predicted, the loss of ambulation with progressive weakness, persistent snoring, witnessed pauses in breathing during sleep, the presence of diaphragmatic breathing or increasing daytime somnolence and behavioural changes.

A polysomnogram is usually undertaken on an annual basis if an abnormality is seen that does not require intervention.

With intervention, perhaps with non-invasive support, as children grow and their weakness progresses they will need an annual polysomnogram.

Non-invasive support usually takes the form of bi-level mask ventilation with a preset inspiratory time and a backup rate if necessary. It is a more complex method of support than nasal continuous positive airway pressure (CPAP).

The settings can be adjusted with the goal of individualising settings based on studies in the sleep laboratory to optimise sleep breathing and normalise gas exchange. It will typically result in the child feeling more refreshed during the day and able to enjoy their waking activities.

This is offered to all patients with nocturnal respiratory failure, but the exact timing of when to introduce it (mild intermittent hypoxia verses hypoxia and CO₂ retention) may vary between centres and can only be established with the cooperation of the patient and their family. Some patients may try mask ventilation and choose not to continue with this therapy.

ADVANCED CARE AND PALLIATIVE CARE
As a young person suffers a progressive decline in mobility, respiratory function and quality of life, there comes a time when consideration of the intensity of therapy and the desired goals need to be well defined.

Clearly, what is needed and, at times, may be overlooked, is the development of a realistic management plan that is inclusive of the young person, their family, the GP, community services and the neuromuscular team.

A useful opportunity is when consideration of non-invasive respiratory support is being discussed. This may or may not be acceptable to the young person. If the non-invasive support is accepted and tolerated, then symptoms of daytime tiredness and fatigue will usually improve.

As weakness progresses, so will ventilatory requirements until a point is reached where hypoxia and hypercarbia cannot be reversed with nocturnal ventilation. Some centres will consider invasive ventilation via a tracheostomy, although this approach is by no means universally acceptable to patients, nor are there adequate facilities available for such provision in Australia.

There are wide-ranging views within the medical profession on whether invasive support should be offered to young people with progressive underlying neurodegenerative conditions.

In this situation, most people will die from a lower respiratory tract infection or from co-existing cardiac problems, including cardiomyopathy and arrhythmias.

Whether or not an active path with non-invasive support is chosen, supportive care is continued. This is discussed commonly in the teenage years. The discussion may be couched in broader terms about the future, and in more specific terms when difficult decisions are made.

It is important to have well-considered plans in advance because at times of acute medical crises, rational thought in all families is one of the first casualties.

Questions of whether to limit therapy to non-invasive support and not to progress to intubation and mechanical ventilation are best considered well ahead of time.

Written, but obviously non-binding, advanced-care directives are helpful in preparing for confronting and emotionally charged decision-making.                

KEY POINTS

• The diagnosis of neuromuscular disorders occurs in the first months and years of life and may involve a combination of a thorough history, detailed physical examination, genetic tests, neurological imaging and, in some cases, muscle or nerve biopsies.
• Regardless of the aetiology of the condition, there is a common pathway with respiratory problems, which manifest with difficulties with airway clearance of secretions, weakened cough, recurrent chest infections and, in more severe cases, respiratory failure.
• The presence of sleep-disordered breathing is common and may relate to obstructive sleep apnoea or hypoventilation.
• The use of non-invasive respiratory support (mask ventilation) may make a considerable difference to the clinical course and quality of life of children with more severe conditions such as spinal muscular atrophy and Duchenne muscular dystrophy.

FURTHER READING
Menezes MP, North KN. Inherited neuromuscular disorders: Pathway to diagnosis. J Paediatr Child Health 2011 doi:10.1111/j.1440-1754.2011.02210.x

Young HK, et al. Outcome of non-invasive ventilation in children with neuromuscular disease. Neurology 2007;68:198-201.

Fitzgerald DA, Follett J, Van Asperen PP. Assessing and managing lung disease and sleep disordered breathing in children with cerebral palsy. Paediatr Respir Rev 2009;10:18-24.