New Therapies for Chest Wall and Spine Disorders in Children.
Gregory J. Redding MD
Professor of Pediatrics, University of Washington School of Medicine
Chief, Pulmonary and Sleep Medicine Division, Seattle Children's Hospital
Seattle, Washington, USA
Key words: scoliosis, thoracic insufficiency children
Mailing Address:
Pulmonary and Sleep Medicine Division, Office A-5937
Seattle Children's Hospital
4800 Sand Point Way N.E.
Seattle, Washington, USA
e-mail: gredding@u.washington.edu
Telephone: 206-987-2174
Fax: 206-987-2639
Traditionally chest wall or thoracic cage disorders were considered independently from spine
disorders. In many cases this is appropriate, such as with pectus deformities. However, there is
an increasing awareness that thoracic and pulmonary disorders can affect spine growth and
configuration and that spine deformities affect thoracic cage, diaphragm, and hence respiratory
growth and function. Recently, the term Thoracic Insufficiency Syndrome has been coined to
describe a variety of spine and thoracic cage disorders that produce “an inability to support
normal respiratory function and postnatal lung growth in children with skeletal immaturity.(1)
TIS results from structural abnormalities of bones in the spine and ribs, known as primary TIS or
it can occur as a result of scoliosis due to neuromuscular conditions producing weakness or
spasticity (secondary TIS). A third category of TIS are thoracic deformities that occur as a result
of surgical resection or congenital absence of ribs, producing a flail chest syndrome.
Changes in spine configuration that contribute to poor chest wall excursion and loss of thoracic
cage compliance include scoliosis, kyphosis, and lordosis of the thoracic region with or without a
cervical or lumbar component. The deformities can vary by site and length along the spine and
can be associated with primary rib anomalies, such as fused ribs. Congenital scoliosis includes
conditions that have structural anomalies of the vertebrae, such as hemi-vertebrae and
unsegmented or block vertebrae. Infantile idiopathic scoliosis can be equally severe but has
normal vertebral anatomy and rib anatomy. In both conditions, the spine can deform
progressively over time, producing progressive restrictive lung disease. Importantly, any one of
these structural features, including the often-used Cobb angle, correlates poorly with functional
respiratory measurements.(2, 3) Another type of thoracic cage deformity in primary TIS includes
disorders that produce a small chest wall. Jeune’s syndrome is the classic example of
circumferential thoracic hypoplasia with a loss of intrathroacic volume for the lung. There are
cases of Jeune’s syndrome that have survived after infancy, suggesting a continuum of severity
exists. A small thorax also occurs in spondylocostal dysplasia and spondylothoracic dysplasia,
previously known together as Jarcho-Levin syndrome. This is a disease of deformed and fewer
vertebrae and ribs, sometimes fused, and hence a shortened thoracic cage in the cephalad-caudad
dimension. Mortality is greater with spondylothoracic dysplasia which also produces a scoliosis.
The physiologic consequences of TIS include loss of vital capacity due to small intrathoracic
space and also loss of chest wall mobility. Lung functions performed under anesthesia have
documented severely reduced total pulmonary compliance (lungs and chest wall combined) with
TIS.(4) Scoliosis also produces a progressive rotational deformity of the spine with rotation of
the ribs producing a thoracic twist. This rotation leads to deformation of intrathoracic contents
with a “windswept” look on transverse images of computerized thoracic tomographic (CT)
scans. The result is development of asymmetry in right and left lung volumes and right and left
lung ventilation and perfusion, as documented by ventilation and perfusion scans.(2) In addition
to the reduced and asymmetric lung volumes, there is evidence of reduced diaphragmatic
excursion by dynamic Magnetic Resonance imaging (MRI) and reduced respiratory muscle force
generation due to abnormal configuration rather than primary muscle weakness per se.
Associated problems related to these functional limitations include poor weight gain, poor sleep
quality, and poor quality of life.(5) More than 50% of children with primary TIS have body
mass indices (using arm span instead of height) of <5%. Children with TIS are also predisposed
to sleep-related hypopneas (but not apneas) with recurrent hypoxemia during sleep and an
increased arousal index.(3) This may also contribute to poor weight gain. The quality of life of
children with TIS is worse than among children with asthma arthritis, and children awaiting heart
transplantation.(5) Physical disability and burden of family care are the domains of the quality
of life survey tools that are most affected by TIS. Late events can include pulmonary
hypertension and cor pulmonale. Approximately 10% of the 320 children who underwent
surgical therapy with the vertical expandible titanium prosthetic rib (VEPTR) were ventilatordependent when first assessed for surgical therapy.
Where once the outcome of these children was considered poor if the chest wall were small or
the spine deformity progressed, the advent of new surgical spine and thoracic devices has
transformed this population of children into a new group with chronic restrictive non-progressive
respiratory disease. There are few studies of natural history of TIS conditions reported in the
literature. The most quoted study is by Pehrsson et al using a national health database to
determine mortality in high risk subgroups of adults with scoliosis.(6) The data is complicated
by inclusion of neuromuscular weakness syndromes (including poliomyelitis) in addition to
primary spinal structural deformities. With this caveat, the authors found that mortality due to
early onset scoliosis (beginning at <8 years of age) increased beginning at 40 years of age and
worsened thereafter. The concept put forth is that lung growth never reached normal values
when postnatal growth of the lung and thorax were complete and that subsequent changes in lung
function due to aging then impacted these people with diminished pulmonary reserve due to
underlying restrictive pulmonary changes.
The traditional method to intervene in early onset progressive scoliosis was to fuse the spine to
halt progression of the deformity. The consequences of this approach depended on the age at
which the spine was fused. Several authors who conducted long-term follow up studies of these
‘treated” patients with fusions have reported severe restrictive lung functions due to reduced
postnatal thoracic vertebral growth due to fusion, and hence reduced thoracic height.(7, 8)
Reduced thoracic height reduces intra-thoracic volume and hence lung volume. Of more
interest, Goldberg reported in a limited series of patients with infantile idiopathic scoliosis that
lung-volume corrected carbon monoxide diffusion capacity was reduced when children required
surgical fusion before the age of 10 years because of progressive scoliotic spine deformity.(8).
This suggests that post-natal alveolar capillary development may be compromised early in life
due to restrictive spine and thoracic cage disease that leads to reduced alveolar-capillary surface
area.
The advent of “growth-sparing” titanium devices that reduce and in part correct spine
deformities due to scoliosis in very young growing children and avoid extensive spine fusion
have revolutionized the surgical approach to children with TIS. There are several types of
growth sparing devices in use currently. They range from the VEPTR device to paraspinal
“growing rods,” and growth guidance systems being developed. The latter approach tethers the
spine to a set of rods that are anchored in the mid-thorax and retard growth of the spine away
from midline over time. The VEPTR and growing rod approaches are currently most widely
used throughout the world. However, the VEPTR device is the only approach were lung
function after surgical implantation and successive expansions have been studied. Importantly,
both the VEPTR and growing rods both require periodic expansion to keep up with somatic
growth of the child and prevent progressive spine deformity. Expansions are currently
performed every 6 months with evidence that regular adjustments produce more vertebral spine
growth during childhood than does adjustment on a as needed basis.(9) These procedures can be
initiated as early as a year of age and require multiple expansions and occasionally replacements
of the devices until early adolescence. There is active research under way to expand these
devices in a non-invasive manner, which would be a tremendous advance and reduce perioperative complications by avoiding recurrent surgical expansions.
The consequences of these new procedures has been to accelerate growth of the vertebral bodies,
and hence thoracic height.(10) Serial assessments of lung function following VEPTR placement
have shown that vital capacity is maintained and continues to increase in absolute terms over 3-4
years.(4) However, the increase in vital capacity, when portrayed as a percentage of predicted
norms, remains the same or diminishes slightly over time. Increase in vital capacity with
repeated rod expansions therefore almost keeps up with postnatal somatic growth. In contrast,
asymmetry in lung function does not predictably change. Serial assessments of respiratory
muscle force generation have not been reported nor has breathing during sleep after surgical
therapy been described. Importantly, these results also demonstrate that further loss of lung
function due to progressive scoliosis is prevented. There is no evidence that ‘catch-up” in lung
function occurs with current spine surgical growth sparing approaches.
The implications to date are that early surgical intervention to prevent loss of lung function may
preserve vital capacity better than late intervention. The consequence of these new therapies is
that children are now living much longer but with chronic pulmonary limitations. The natural
course of TIS has been changed for the better but a new population of children with chronic lung,
spine, and thoracic disease has been created that will require long-term pulmonary care.
1.
Campbell R, Smith MD. Thoracic insufficiency syndrome and exotic scoliosis. J Bone
Joint Surg Am 2007; 89:108-22.
2.
Redding G, Song K, Inscore S, Effmann EL, Campbell R. Lung function asymmetry in
children with congenital and infantile scoliosis. Spine 2007; 8:639-44.
3.
Striegl A, Chen M, Kifle Y, Song K. Sleep-related breathing disorders in children with
thoracic insufficiency syndrome: Impact of neuromuscular disease. Pediatr Pulmonol (Accepted)
2010; 00:0-.
4.
Motoyama EK, Yang CI, Deeney VF. Thoracic malformation with early-onset scoliosis:
Effect of serial VEPTR expansion thoracoplasty on lung growth and function in children.
Paediatr Respir Rev 2009; 10:12-7.
5.
Vitale MG, Matsumoto H, Roye DP, Gomez JA, Betz RR, Emans JB, et al. Health-
related quality of life in children with thoracic insufficiency syndrome. J Pediatr Orthop 2008;
28:239-43.
6.
Pehrsson K, Bake B, Larsson S, Nachemson A. Lung function in adult idiopathic
scoliosis: a 20 year follow up. Thorax 1991; 46:474-8.
7.
Karol LA, Johnston C, Mladenov K, Schochet P, Walters P, Browne RH. Pulmonary
function following early thoracic fusion in non-neuromuscular scoliosis. J Bone Joint Surg Am
2008; 90:1272-81.
8.
Goldberg CJ, Gillic I, Connaughton O, Moore DP, Fogarty EE, Canny GJ, et al.
Respiratory function and cosmesis at maturity in infantile-onset scoliosis. Spine 2003; 28:2397406.
9.
Thompson GH, Akbarnia BA, Campbell R. Growing rod techniques in early-onset
scoliosis. J Pediatr Orthop 2007; 27:354-61.
10.
Campbell RM, Hell-Vocke AK. Growth of the thoracic spine in congenital scoliosis after
expansion thoracoplasty. J Bone Joint Surg Am 2003; 85-A:409-20.