++
Primary disease of the muscle or nerve can have significant effects
on chest wall function. The two most common neuromuscular disorders
in children are Duchenne muscular dystrophy and spinal muscular
atrophy. Other pediatric neuromuscular disorders that can result
in weakness of the respiratory muscles and lead to secondary chest
wall disorders include spinal cord injury, Guillain-Barré syndrome,
and other muscular dystrophies (Becker, congenital, limb-gird muscular
dystrophy). Neuromuscular disorders that involve the respiratory
musculature lead to three kinds of complications: recurrent pneumonia
because ability to cough is lost; ventilatory failure during sleep
and eventually during awake time; and development of a restrictive
chest wall due to a combination of chest wall rigidity and scoliosis.
The combination of respiratory muscle weakness and chest wall rigidity
limits even mechanical support of breathing and coughing. Newer
approaches to managing respiratory muscle weakness in these disorders
have changed the natural history of these diseases and have improved
outcomes.
+++
Duchenne Muscular Dystrophy
++
Duchenne muscular dystrophy (see Chapter 572)
is caused by a mutation in the dystrophin gene and leads to a loss
of the protein dystrophin, which links the sarcolemmal cytoskeleton
to the extracellular matrix. This loss creates an increase in membrane fragility
and repetitive injury to the muscle cells, which causes scarring
and progressive weakness. Duchenne muscular dystrophy is X-linked
and occurs in approximately 1 in 3000 boys. Although the majority of
involvement is in the skeletal muscle, cardiac muscle involvement
is common. Although there is no cure, systemic corticosteroids have
been shown to slow the progression of the muscle disease. Loss of ambulation
tends to occur at the end of the first decade of life. After the
patient loses ambulation, the respiratory complications of this
disease begin. These complications include scoliosis, loss of effective cough,
obstructive apnea, and the development of ventilatory failure.
++
Scoliosis is less common in patients who are treated with systemic
corticosteroids. Bracing has been shown to be ineffective, and surgical
correction with rod placement is indicated once the Cobb angle reaches
30 degrees.
++
Obstructive sleep apnea has been reported prior to the development
of respiratory insufficiency during sleep; this is probably related
to a combination of obesity and upper airway muscular weakness.6
++
Lung function should be monitored, especially after loss of ambulation,
with spirometry, lung volumes, and respiratory muscle strength measurements.
The usual pattern is restrictive lung disease with increased residual
volume secondary to weaker muscles of expiration compared to inspiration.
These patients are unable to actively expire to lung volumes below
functional residual capacity.
++
When the vital capacity falls below 30% of predicted
value, there is a high incidence of respiratory failure in sleep.6 Elevation
of the end-tidal pCO2 level to 45 mm Hg and higher while
awake also predicts respiratory insufficiency in sleep.7 Eventually,
daytime respiratory failure occurs. Each of these stages in the
Duchenne patient can be effectively managed in a noninvasive manner.8 Mechanical
insufflation-exsufflation has been proven effective and safe in
this population to prevent pneumonia. Noninvasive positive-pressure
ventilation with a mask during sleep and a mouthpiece during the
day can be used to support ventilation, avoiding the need for a
tracheotomy.
+++
Spinal Muscular Atrophy
++
Spinal muscular atrophy (SMA) is a congenital disorder of the
anterior horn cell. Clinical features of SMA include hypotonia;
muscle weakness, including extensive involvement of the intercostal
muscles; muscle atrophy; and fasciculations. Muscle weakness is
symmetric, greater proximally, and typically more profound in the
legs than the arms (see Chapter 570).
++
SMA is classified into three types (SMA type I, type II, and
type III), which are best distinguished by the age of onset and
clinical course. SMA type I (Werdnig-Hoffmann disease or severe
infantile SMA) is the most severe disorder and generally presents
before 6 months of age with profound hypotonia and weakness, swallowing
dysfunction, and tongue fasciculations; the disease generally results
in respiratory insufficiency and death by 2 years of age unless
long-term mechanical ventilation is employed.
++
SMA type II (intermediate or chronic infantile SMA) has an estimated
incidence of 1:15,000 to 1:25,000 live births. Children with SMA
type II may initially achieve normal motor milestones, but these
are lost during the first 2 years of life. Median age of death is
12 years unless long-term mechanical ventilation is employed. Children
with SMA type II may not be able to sit independently. Weakness
may be static for long periods, with progression of weakness during
intercurrent illness or immobilization. Bulbar musculature is generally
intact. The onset of SMA type III (Kugelberg-Welander or mild SMA)
is usually between 2 and 17 years of age; these children are usually
able to stand and walk unaided.
++
Clinical examination, laboratory evaluation (including normal
serum creatine kinase), electromyogram, and muscle biopsy were used
in the diagnosis of SMA. The discovery of the gene in 1995 resulted
in diagnosis by gene mutation screening alone in 95% of
cases. Laboratory data demonstrate subtle differences in the SMA
types. Therefore, Dubowitz uses functional status to distinguish
the types (ie, in severe SMA, children are unable to sit; in intermediate
SMA, children are able to sit unsupported but cannot stand or walk
unaided; with mild SMA, children are able to stand and walk unaided).9
++
Unlike Duchenne muscular dystrophy, SMA I and II is characterized
by early and severe involvement of the intercostal muscles. As a
result, there is greater chest wall involvement in SMA patients.
These individuals tend to develop a bell-shaped chest wall, as the
action of the diaphragm, which tends to cause an indrawing of the
compliant chest wall of the infant during inspiration, is not balanced
by opposing action of the intercostal muscles. A pectus excavatum deformity
occurs simultaneously. Bach has shown that positive-pressure ventilation
has remodeled the chest wall and normalized the chest wall’s
shape.10
++
Management of children with SMA includes aggressive respiratory,
nutritional, and orthopedic management.11 Children with SMA
are at risk for nocturnal hypoventilation. Evaluation includes assessment
of lung function with spirometry, lung volumes, respiratory muscle
strength measurements, and pulse oximetry. Hypoventilation is best
evaluated by nocturnal polysomnography with multiple channel measurements,
including end-tidal CO2 and pulse oximetry. Hypoventilation
is managed using respiratory support such as noninvasive positive-pressure
ventilation while sleeping. During viral respiratory infections,
aggressive airway clearance of increased secretions is critical
to the child’s survival, using assisted coughing techniques
(mechanical insufflation-exsufflation).
++
Progressive scoliosis is managed initially with bracing to facilitate
sitting, although improper bracing can actually impair ventilation.
Scoliosis may require surgical correction. These interventions contribute significantly
to quality of life.
++
The option of noninvasive ventilation versus tracheostomy and
long-term mechanical ventilation should be discussed with patients
and family members well before the onset of respiratory failure.
+++
Guillain-Barré Syndrome
++
Guillain-Barré syndrome is an acute inflammatory ascending
demyelinating disease of the peripheral nervous system. The vast
majority of affected individuals have a history of recent nonspecific
illness, but the syndrome is also associated with cytomegalovirus
and Epstein-Barr virus infection. The ascending paralysis and weakness
progresses, typically over hours to several days. Involvement of
the diaphragm and intercostal muscles results in hypoventilation,
and tidal breathing may occur well below the patient’s
usual functional residual capacity. Progressive weakness involving
the cranial nerves may result in laryngeal and vocal cord dysfunction
with resulting upper airway obstruction. Respiratory support is
required when hypoventilation occurs or when the individual cannot
clear lower airway secretions. Approximately 15% of children
with Guillain-Barré syndrome will require mechanical ventilation
for respiratory failure. Serial monitoring of vital capacity and
respiratory muscle function is critical. Treatment includes intravenous
immunoglobulin, corticosteroids, and aggressive respiratory support.
Recovery ranges from days to months and is usually complete.12
+++
Diaphragmatic Paralysis
++
Unilateral and bilateral paralysis of the diaphragm is rare in
pediatric patients. However, it may be overlooked during the evaluation
of infants with unexplained hypoxemia, atelectasis, or tachypnea.
In the neonatal period, diaphragm paralysis is most frequently caused
by complications during delivery or following thoracic or neck surgery.
The phrenic nerve fibers arise from C3, C4, and C5. The superficial
location of the phrenic nerve in the neck and within the thorax
contributes to the risk of injury during delivery. During cardiovascular
surgery, the phrenic nerve may be injured by cooling, stretching,
or accidental direct injury. In addition, high-cervical-spine trauma
or tumors can result in diaphragm paralysis, and neuromuscular disease
may be complicated by diaphragm paralysis.
++
The neonate is at much greater risk of respiratory compromise
from diaphragm paralysis. Older children and adults tolerate unilateral
diaphragm paralysis well. Diaphragm paralysis should be considered
in any infant who has unexplained respiratory distress with tachypnea
and hypoxemia, especially after a difficult delivery, or in a child
following thoracotomy who fails to wean from mechanical ventilation. Chest
radiographs demonstrating an elevated hemidiaphragm or elevation
of both diaphragms are suspect for diaphragm paralysis. Diagnosis
is made by ultrasound or fluoroscopy, which shows very little movement
with breathing or shows paradoxic (upward) movement of the diaphragm
with inspiration. Transcervical nerve stimulation may be helpful
in determining whether the phrenic nerve is intact.
++
Following thoracic or neck surgery, recovery may occur in up
to 90% of patients over about 6 months if the phrenic nerve
is intact. Infants may require positive-pressure ventilation, either
invasively or noninvasively, until the diaphragm recovers. In individuals
with permanent unilateral diaphragm paralysis, diaphragm plication
may be helpful. Management options include respiratory support until
the diaphragm recovers and surgical plication if recovery is incomplete.
Indications for plication include persistent respiratory failure
and paradoxical cephalad movement of the affected diaphragm during
inspiration. This surgery can be performed via thoracotomy or video-assisted
thoracoscopic surgery.13 In individuals with irreversible
bilateral diaphragm paralysis (eg, spinal cord injury or neuromuscular
disease), respiratory support with mechanical ventilation will be
required. Older children and adult patients tolerate the diaphragm
limitation relatively well, and they may require only nocturnal
respiratory support.