early-onset scoliosis: a review of history, current ... · pediatrics volume 137 , number 1 ,...
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Early-Onset Scoliosis: A Review of History, Current Treatment, and Future DirectionsScott Yang, MD,a,b Lindsay M Andras, MD,a Gregory J Redding, MD,c David L Skaggs, MD, MMMa
aChildren’s Orthopaedic Center, Children’s Hospital
Los Angeles, Los Angeles, California; bDepartment of
Orthopaedic Surgery, University of Virginia Health System,
Charlottesville, Virginia; and cDepartment of Pediatrics,
Division of Pulmonary and Sleep Medicine, Seattle
Children’s Hospital, Seattle, Washington
Dr Yang drafted the initial manuscript and edited
the fi nal manuscript; Drs Andras and Redding
provided critical revisions to the manuscript; Dr
Skaggs provided overall supervision and critical
revisions to the manuscript; and all authors
approved the fi nal manuscript as submitted.
The treatment of early-onset scoliosis
(EOS) remains a challenging and
rapidly evolving area of pediatric
orthopedics. EOS is defined as
a curvature of the spine ≥10°
in the frontal plane with onset
before 10 years of age (Fig 1).1,2
The management of EOS requires
consideration of the interrelated
growth of the spine and thorax and
their impact on lung development.
In addition, EOS is often associated
with other comorbid conditions that
increase the complexity of managing
the spinal deformity.
EOS includes an inhomogeneous
grouping of patients, because the
etiology of the spinal deformity
may be idiopathic, associated with
underlying systemic syndromes,
secondary to a neuromuscular
condition, or caused by a structural
congenital spinal deformity (Table
1).3 The true prevalence of EOS is
unknown, although idiopathic EOS
accounts for <1% of all scoliosis
cases.4 Congenital scoliosis results
from abnormalities of vertebral
development in utero and may include
single or multiple hemivertebrae or
segmentation defects with or without
associated rib fusion. Congenital
scoliosis is often progressive and may
necessitate early, more aggressive
treatment. Idiopathic EOS in infants
abstractEarly-onset scoliosis (EOS) is defined as curvature of the spine in children
>10° with onset before age 10 years. Young children with EOS are at risk
for impaired pulmonary function because of the high risk of progressive
spinal deformity and thoracic constraints during a critical time of lung
development. The treatment of EOS is very challenging because the
population is inhomogeneous, often medically complex, and often needs
multiple surgeries. In the past, early spinal fusion was performed in
children with severe progressive EOS, which corrected scoliosis but limited
spine and thoracic growth and resulted in poor pulmonary outcomes.
The current goal in treatment of EOS is to maximize growth of the spine
and thorax by controlling the spinal deformity, with the aim of promoting
normal lung development and pulmonary function. Bracing and casting
may improve on the natural history of progression of spinal deformity
and are often used to delay surgical intervention or in some cases obviate
surgery. Recent advances in surgical implants and techniques have led to
the development of growth-friendly implants, which have replaced early
spine fusion as the surgical treatment of choice. Treatment with growth-
friendly implants usually requires multiple surgeries and is associated with
frequent complications. However, growth-friendly spine surgery has been
shown to correct spinal deformity while allowing growth of the spine and
subsequently lung growth.
STATE-OF-THE-ART REVIEW ARTICLEPEDIATRICS Volume 137 , number 1 , January 2016 :e 20150709
To cite: Yang S, Andras LM, Redding GJ, et al.
Early-Onset Scoliosis: A Review of History, Current
Treatment, and Future Directions. Pediatrics.
2016;137(1):e20150709
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YANG et al
occurs in children ≤3 years of age
and has a variable course over time.
A unique feature of idiopathic EOS
in infants is that it often improves
spontaneously.5,6 Idiopathic EOS in
juveniles occurs in children aged 4
to 10 years. Among children with
neuromuscular disorders, scoliosis
is common and compounds the
restrictive lung disease produced
by respiratory muscle weakness.
Treatment strategies and duration
differ significantly based on
both etiology and the amount of
anticipated growth remaining. The
younger the child, the greater the
risk that the spinal deformity will
affect pulmonary development and
function.
GROWTH OF THE SPINE AND LUNG DEVELOPMENT
The spine grows most rapidly in
the first 5 years, with an average
T1 to S1 segment length increase
of 10 cm during this time (2 cm/
year). After the first 5 years, there
is a slower T1 to S1 growth from
age 5 to 10 years of ~5 cm until
adolescence (1 cm/year). From
age 10 years to adulthood, T1 to
S1 grows an additional 10 cm; this
includes the adolescent growth spurt
(2 cm/year).7–9 Because growth
can promote the progression of the
deformity, patients with EOS are at
greatest risk for progression of spinal
deformity in the first few years of life
and during the adolescent growth
spurt.
In EOS, the progressive spinal
deformity occurs during a critical
time of lung development. The
number of alveoli and lung volume
increase most rapidly in the first
several years and continue to
increase at a lower rate during
adolescence and adulthood (Fig
2).10–12 Animal models of EOS
produced early in life demonstrate
alveolar simplification and reduced
number, producing an example of
postnatal hypoplasia.13 Autopsies of
children dying of EOS report similar
alveolar features and pulmonary
vascular remodeling associated with
pulmonary hypertension.14 Lung
function studies of children with EOS
demonstrate a variable severity of
restrictive lung disease caused by
small lung volumes, reduced chest
wall compliance, and respiratory
muscle dysfunction.15 The concept
of thoracic insufficiency syndrome
(TIS), popularized by Campbell et
al,16 is defined as the inability of the
thorax to support normal respiratory
function and lung development in
growing children. Because of scoliosis
progression early in life, patients
with severe EOS can potentially
develop TIS. TIS has been associated
with poorer quality of life scores than
those of childhood epilepsy, heart
disease, and cancer.17
The natural history of untreated
EOS is associated with significant
morbidity and often profound
cardiopulmonary compromise,
including respiratory failure and
cor pulmonale. A Swedish study
comparing expected population
death rates demonstrated more than
twice the mortality rate by age 40
in patients with EOS compared with
that of the general population.18
Consequently, the fundamental
principle of treating EOS is to foster
normal respiratory development
and maximize spinal growth while
preventing additional deformity that
can lead to TIS.
HISTORY OF TREATMENT STRATEGIES: WHAT WE HAVE LEARNED
Before the introduction of spinal
implants, the historical treatment of
EOS consisted of casting or bracing
the spine and thorax. Although
casting for scoliosis has been
performed for centuries, it fell out
of favor as the primary treatment
of scoliosis because of concerns
that casting deformed the ribs. Paul
Harrington introduced a spinal
implant for scoliosis in the 1960s
that provided a surgical alternative.
In these cases, the rod was used to
2
FIGURE 1Posteroanterior (A) and lateral (B) radiographs of a 4-year-old boy whose untreated scoliosis had rapidly progressed to 110° and who developed severe kyphosis. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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PEDIATRICS Volume 137 , number 1 , January 2016
surgically correct scoliosis without
fusion by applying distraction
across the concavity of the curve.19
Harrington rods improved curves
in a 2-dimensional plane, although
this technique often led to a flat
back deformity. Implant failure and
dislodgment with this method were
high, and its use was limited.
Early spinal fusion to halt deformity
in EOS then became the preferred
treatment, because a short and
straight spine was thought to
be superior to a progressively
crooked spine. Subsequent studies
demonstrated that early spinal
fusion, which prevents continued
spinal growth of the fused region,
limits intrathoracic volume and
hence lung volume. As a result,
children developed severe restrictive
lung disease with continued growth.
Patients with idiopathic EOS who
underwent spinal fusion at a mean
age of 4.1 years demonstrated mean
forced vital capacity (FVC) of 41% of
normal when evaluated at skeletal
maturity, whereas patients who
underwent fusion at a mean age of
12.9 years demonstrated mean FVC
of 68% of normal.20 In 1 study, the
reduction in FVC ≥5 years after spine
fusion directly correlated with the
number of thoracic spinal segments
fused.21 Early posterior spinal fusion
techniques have often led to the
crankshaft phenomenon, in which
the anterior column of the immature
spine continues to grow, leading to
progressive deformity. Consequently,
new treatment strategies have been
developed that allow or promote
spinal growth, usually referred to
as growth-friendly techniques.22
At worst these techniques may be
thought of as delaying the need
for a spine fusion to allow spinal
growth, and at best they may cure
the scoliosis or avoid the need for a
spinal fusion.
One exception to avoiding early
spinal fusion is congenital scoliosis in
which the spine deformity is limited
to a small number of vertebrae.
The classic example of congenital
scoliosis that requires early fusion is
the case of a hemivertebra causing
progressive scoliosis (Fig 3). In such
cases early fusion (with or without
excision of the hemivertebrae)
can often correct the scoliosis in
1 surgery, with a fusion of only
2 vertebrae. This procedure is
generally performed around the age
of 3 to 6 years.
CURRENT TREATMENT STRATEGIES: NONOPERATIVE
Nonoperative treatment of EOS
consists of bracing or casting.
Bracing can be considered for mild
progressive curves, although its
efficacy remains unproven in EOS,23
and ensuring compliance with brace
wear can be difficult in young children.
Commonly used braces are variants of
a custom-molded thoracolumbosacral
orthosis. Braces are often used to
maintain correction obtained from
serial casting or delay surgical
intervention. Several case series have
shown that 74% to 92% of idiopathic
EOS in infants spontaneously
resolves.6,24 For idiopathic EOS in
3
TABLE 1 Summary of the Different Types of EOS and Their Unique Features
Types of EOS Characteristics Associated Diagnoses Treatment Considerations
Congenital Structural abnormality of
the spine or thorax present
at birth.
Cardiac, renal
abnormalities
Hemivertebrae excision.
Short-segment early
spinal fusion in select
cases in this group
may be the exception to
growth-friendly spine
surgery.
Failure of formation (eg,
hemivertebra).
Other musculoskeletal
abnormalities (upper
limb, club foot)
Failure of segmentation (eg,
fused vertebra or ribs).
Associated with VATER/
VACTERL syndromes
Intraspinal abnormalities
(ie, diastematomyelia,
tethered cord)
Neuromuscular Abnormalities in muscular
tone lead to scoliosis.
Examples: Cerebral palsy,
muscular dystrophies,
myopathies, spinal cord
injuries
Generally higher-risk
surgical patients with
medical comorbidities
(eg, respiratory,
gastrointestinal).
Often a long, sweeping
scoliosis curve.
Syndromic Includes any other syndrome
associated scoliosis
(excluding neuromuscular
or congenital scoliosis
syndromes).
Examples: Connective
tissue disorders,
Marfan syndrome,
neurofi bromatosis,
skeletal dysplasias,
Prader–Willi syndrome
Each syndrome has
unique considerations
(eg, neurofi bromatosis
may have dural ectasia,
making spinal implants
more challenging to
place.
Idiopathic Scoliosis without a known
attributable cause.
Higher incidence
of Arnold–Chiari
malformation and
syringomyelia compared
with adolescent idiopathic
scoliosis
Generally healthier
children.
Infantile (diagnosed <3 y):
Many milder curves will
resolve but need observation.
Casting shown to resolve
some infantile curves.
Juvenile (diagnosed 4–10 y):
Often left sided curves. Slight
male predominance.
Surgery often needed
despite often long-term
casting or brace wear.
Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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infants with unresolved progressive
curves, Mehta25 demonstrated that
casting may be effective in completely
resolving some curves, especially
those of lower magnitude. Because
casting has proven to be a safe method
to manage idiopathic EOS, there
has been a resurgence of interest in
expanding traditional cast methods
to treat multiple subtypes of EOS to
avoid the risks of surgery and early
spine fusion (Fig 4). The cast is applied
to the torso under anesthesia while
the child is in traction, elongating
the spine. The cast is molded while
the child’s torso is derotated and
flexed away from the concavity of the
curve. Casts are changed every 8 to
12 weeks. For curves that resolved
or stabilized in a cast, bracing is often
used to help maintain the correction
through skeletal maturity. If there
is progression despite bracing,
additional casting may be used to
attempt to regain the correction.
In other cases, growth-friendly
implants or fusion may be the most
appropriate step depending on the
patient’s age and curve severity.
Serial casting applied to young
children with nonidiopathic EOS has
been shown to be an effective way
to delay surgical treatment.26–28 In 1
study, curve resolution was rare with
serial casting in the nonidiopathic
EOS, but progression of the curve
was controlled sufficiently to delay
spine surgery for at least 2 years.
Normal longitudinal growth of
the spine was observed while the
patient was in the cast.28 Based on
current evidence, a trial of casting in
EOS regardless of curve etiology is
considered a treatment option. The
specific indications for the threshold
to institute cast treatment continue
to vary between institutions but are
generally considered for EOS curves
>25°, with >10° of documented
progression.
CURRENT TREATMENT STRATEGIES: SURGICAL
The surgical treatment strategy for
EOS has evolved significantly over
the past decade with the use of
modern growth-friendly implants.
These implants attempt to maximize
the growth of the spine and thorax
while controlling curve progression
to preserve normal lung volume.
Growth-friendly implants can be
classified into 3 distinct subtypes:
distraction-based, guided growth,
and compression-based strategies.22
Distraction-Based Implants
Distraction-based implants are the
most common devices used in EOS.
They apply traction to the spinal
column between proximal and
distal anchors joined by expandable
rods. The rods are periodically
lengthened as the child grows to
maintain spine curve correction.
Four types of implants have been
used: the traditional growing rod
(TGR), vertical expandable prosthetic
titanium rib (VEPTR) device, hybrid
systems, and magnetically controlled
growing rod (MCGR).
Growing Rod
The TGR incorporates proximal and
distal hook or screw anchors on the
spine, joined by rods with connectors
that allow serial distractions between
the rods (Fig 5). Limited fusion is
performed at the proximal and distal
anchor sites on the spine to provide
4
FIGURE 2Composite plots of total alveolar number, T1–S1 segment growth from birth, and mean lung volume with age. The number of alveoli, mean lung volume, and spinal growth increase rapidly in the fi rst few years of life. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
FIGURE 3Preoperative radiograph (A) and CT scan (B) of a patient with a hemivertebrae (red arrow). Intraoperative images demonstrating correction of the deformity with a hemivertebrectomy (C). Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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solid sites for spine distraction.
The area between the anchors is
intentionally not fused, allowing
motion and growth through this
region. Lengthenings are typically
performed at ~6-month intervals.
Akbarnia et al29 reported on the
use of TGRs for EOS in 24 patients,
resulting in improvement of coronal
plane major curves from 82° to
36°, with 1.2 cm growth in T1 to
S1 length per year at mean 4-year
follow-up. Akbarnia et al30 also
demonstrated that patients whose
spines were lengthened at ≤6-month
intervals had significantly higher
annual T1 to S1 growth rate of 1.8
cm/year, compared with 1.0 cm/
year in patients whose spines were
lengthened less frequently. This
finding has led many to believe that
distraction may actually promote
vertebral growth.
VEPTR
Developed by Bob Campbell, VEPTRs
use ribs as anchors, and sometimes
the spine and pelvis as well. VEPTRs
are generally thought of as primarily
providing thoracic expansion,
compared with growing rods,
which primarily provide control
of scoliosis. In reality, thoracic and
spinal deformities are closely linked.
Similar to other distraction-based
systems, these constructs undergo
recurrent surgical expansion (Fig 6).
Original descriptions of the VEPTR
technique recommended incising
between ribs to maximize thoracic
expansion, but concerns of scarring
and stiffening of the chest wall
led most surgeons to cut between
the ribs only in cases of multiple
fused ribs. VEPTR treatment has
demonstrated continued spinal
growth with serial expansions (mean
71 mm over 4 lengthenings) while
improving the coronal curve.31,32
Hybrid
A hybrid distraction-based strategy
incorporates the VEPTR concept of
using ribs as anchor sites but also
uses traditional spinal implants,
as in the TGR system. Traditional
spinal hooks are placed proximally
along the ribs (Fig 7). As in the
TGR strategy, the distal anchor
site is incorporated by a fusion,
5
FIGURE 4A, Radiograph of a 29-month-old girl with idiopathic EOS and a curve of 47°. B, In-cast radiograph shows curve corrected to 18° with the initial cast. C, Like many children she continued to be quite active despite the cast. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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and lengthening is performed at a
connector between the rods. The
advantage of this technique is that
it avoids fusion of the proximal
anchor site of the thoracic spine,
potentially allowing more total
growth of the thorax. Furthermore,
rib anchors without traditional rigid
fusion at the proximal anchor site
allow some motion of the spinal
implant construct. This feature may
reduce the stress and rigidity of the
distraction system across an unfused
mobile spine. Consequently, use of
a hybrid system with proximal rib
anchors has been associated with
a decrease in the incidence of rod
breakage.33
MCGR
Recently the US Food and Drug
Administration cleared the use
of MCGRs, which can lengthen
nonsurgically without anesthesia
after the initial implantation.34,35
This implant is similar to other
growing rod constructs with distal
spine anchors and proximal rib or
spine anchors that are connected by
telescoping rods. This telescoping
portion contains an internal magnet
that can be lengthened from an
external remote control (Fig 8).
Because of the noninvasive nature
of lengthening, it is also possible
to distract at shorter intervals.
Preliminary studies of MCGRs
have been met with optimism
with respect to achieving the same
results of TGRs.34–36 Dannawi et
al34 demonstrated that the mean
coronal Cobb angle improved from
69° to 41° after MCGRs with a mean
of 4.8 distractions per patient were
used over 15 months. The T1 to S1
length increased a mean of 3.5 cm
during this time period. A study
comparing 12 MCGR- and TGR-
treated patients demonstrated no
significant difference in spine length
gains, but there were 57 fewer
surgical procedures in the MCGR
group.37 Although MCGR avoids the
need for repeat surgical intervention
for routine lengthenings, long-term
data are not yet available for this
technique. Similar to growth-friendly
implants, the complication rate is
high: 33% of patients treated with
MCGR within 2 years of follow-up.37
6
FIGURE 5Preoperative (A) and postoperative (B) radiographs of patient with traditional spine-to-spine growing rods. Radiographs obtained 5 years after the initial placement of growing rods (C) show that the scoliosis continues to be well controlled. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
FIGURE 6Postoperative radiograph of an 8-year-old boy with VATER syndrome with congenital scoliosis, multiple rib fusions, and thoracic insuffi ciency syndrome that was treated with a VEPTR construct. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
FIGURE 7A, Preoperative posteroanterior and lateral radiograph of a 4-year-old boy with severe progressive scoliosis and an 85° curve. He was not a casting candidate because of his restrictive lung disease. B, Postoperative radiograph showing a hybrid growing rod construct (rib to spine) with improvement to 37°. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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Complications of Distraction-Based Implants
Regardless of the implant used for
distraction-based treatment of the
growing spine, all strategies are
associated with a high complication
rate.29,30,38–43 Implant complications
such as anchor malfunction (pullout
from the spine, erosion through the
rib) and rod breakage are common
(Fig 9). Distraction-based posterior
implants often produce kyphosis,
which may result in an unfavorable
overall sagittal plane balance. Wound
complications are also common
because of the prominence of
implants under the skin and poor
healing potential in small, thin, and
often chronically malnourished
patients with EOS (Fig 10). At least 1
complication of treatment has been
reported to occur in 58% to 86%
of patients undergoing distraction-
based treatment, leading to multiple
unplanned surgical procedures.38,43,44
Among patients with complications,
1 study demonstrated a mean of
2.2 complications per patient.38
Application of stiff implants on an
unfused spine that continues to have
motion ultimately leads to fatigue
failure of the implants. Risk factors
for implant failures include severe
thoracic kyphosis that produces
proximal anchor pullout and
increased number of lengthening
procedures.40 Implantation
strategies are being critically
evaluated to decrease the incidence
of implant-related complications. A
comparison study of complications
in TGRs, hybrid proximal rib anchor
systems, and VEPTR treatments
in EOS demonstrated a trend
toward decreased implant-related
complications in the hybrid system.43
Hooks are not as rigidly fixed to
the spine compared with screws,
theoretically allowing some motion
and dispersion of stress, decreasing
fatigue-related implant failures.
Yamaguchi et al33 demonstrated
6% rod breakage in proximal rib-
anchored growing rods, compared
with 29% in proximal spine-
anchored growing rods at a mean
56-month follow-up.
The multiple surgeries needed for
treatment with distraction-based
implants are associated with adverse
outcomes. Each lengthening surgery
has been shown to increase the
risk of deep infection 3.3 times in
EOS.41 The length gained from serial
lengthening has also been shown to
follow a law of diminishing returns,
with decreased spinal length gained
after each lengthening because of
increased stiffness of the spine.45,46
Autofusion of the spine has been
also described after repeated
lengthenings.47 Ultimately, the utility
of lengthening may be minimal after
the sixth or seventh lengthening
procedure, limiting the potential
spinal growth to 4 to 5 years after
initial surgery.
In addition to the physical effects
on the spine, there are significant
psychological effects from
distraction-based treatment. Patients
with repeated surgery in EOS
demonstrate abnormal psychosocial
scores, with a positive correlation
between behavioral problems and
the number of repetitive surgeries.42
Repeated general anesthesia in
children may cause detrimental
neurocognitive effects, based on
animal and preclinical studies,
although this remains an area of
controversy.48–50 New technologies,
such as MCGRs that obviate surgical
lengthenings, will probably help
minimize the total number of
exposures to anesthesia in EOS.
Guided Growth Implants
In guided growth techniques, the
spine is straightened with spinal
implants that allow the vertebrae
to grow along the path of the spinal
implants. The original guided growth
system used Luque wires wrapped
around the lamina of each vertebrae,
which were wrapped around straight
rods that corrected scoliosis and then
permitted guided growth as the wires
slid along the rods. This technique
was found to lead to spontaneous
fusion and limited spinal growth. A
more recent type of guided growth
implant, called the Shilla technique,
has been developed by Richard
McCarthy. In this technique, screws
are placed into vertebrae with
minimal dissection in the hopes of
avoiding spontaneous fusion and
allowing 3-dimensional correction of
7
FIGURE 8A, Preoperative anteroposterior radiograph of a 7-year-old girl with spinal muscular atrophy and 100° thoracolumbar curve. B, Postoperative posteroanterior radiograph demonstrating a construct including the MCGR device. C, Model demonstrating an MCGR device. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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the spinal deformity and permitting
growth along the rods (Fig 11).
The major advantage of guided
growth techniques over growing
rods is that children avoid multiple
surgical lengthenings. A recent study
comparing the Shilla technique
with growing rods demonstrated
that patients treated with the Shilla
technique had fewer surgeries (2.8)
compared with growing rods (7.4)
in >4-year mean follow-up. Shilla
resulted in less spinal growth and
less correction of scoliosis, with
similar complication rates to growing
rods.51
Compression-Based Implants
Compression-based implants involve
correcting scoliosis by stopping
the growth of the convex side of
the scoliosis without fusion while
allowing growth of the concave
side of the curve. This correction
is accomplished by placing staples,
tethers, or other devices across the
growth plates of the vertebrae from
an anterior approach on the convex
side of the scoliosis. Although there
is 1 device approved by the US Food
and Drug Administration, tethers
and staples are most commonly
used off label. Several case series on
compression-based implants have
demonstrated curve correction with
growth in patients who underwent
surgery at age <10 years.52,53 There
have been cases of overcorrection
with compression-based implants,
in which the curve corrects and then
develops in the opposite direction.
Therefore, this technique is generally
reserved for patients with limited
growth remaining, such as 9- to
10-year-olds. Additional concerns
include the potential pulmonary
impact of ≥1 transthoracic surgeries.
Serial measures of lung function in
older children with scoliosis treated
with transthoracic spine surgery
have shown greater loss of function
postoperatively when the thorax is
opened.54
PULMONARY OUTCOMES OF RECENT EOS TREATMENT
The study of pulmonary function in
this patient population is extremely
challenging, complicated by the fact
that many of these patients start
treatment of EOS before they are old
enough to undergo formal pulmonary
function tests (PFTs). Much of the
current literature evaluating the
pulmonary outcomes after growth-
friendly spine surgery has been
based on VEPTR in children >6
years old. PFTs have been measured
in both awake and anesthetized
patients. Computed tomography has
also been used to measure thoracic
volumes as a surrogate for PFTs.
Studies of lung function in EOS have
not compared treatment strategies
or different devices and are often
small, descriptive case series. In 1
such series, 10 children with EOS
(median age 4.3 years) demonstrated
increased mean annual absolute
FVC of 27% of predicted norms and
maintenance of FVC as a percentage
of normal after VEPTR treatment at
a mean 22 months of follow-up.55
With longer periods of follow-up
(mean 6 years) during and at the
completion of growing construct
surgery, FVC as a percentage of
normal declined by an average of
28%.56,57 There are no untreated
control groups to assess what loss of
lung function might have occurred in
the natural progression of the spine
deformities. The implication of these
studies is that lung function is not
normalized or predictably improved
after treatments for EOS but that
progressive loss of lung function may
be reduced with treatment.
Surrogate pulmonary outcomes
that do not require voluntary
effort by young children have also
been reported. Several studies
used weight gain as an indirect
marker of improved pulmonary
function and found that up to 50%
of patients with EOS demonstrated
a mean 24- to 26-percentage-
point improvement after VEPTR
or growing rod treatment.58,59
Overnight polysomnography in
children with EOS demonstrates an
increased Apnea–Hypopnea Index
8
FIGURE 9Radiograph demonstrating a broken rod with traditional spine-to-spine growing rods, identifi ed by the red arrow. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
FIGURE 10Clinical photo showing marked hardware prominence in a thin child with EOS. Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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and hypoxemia associated with
hypopneic events.60 Serial measures
of breathing during sleep before
and after treatment of EOS may also
prove useful as an indirect measure
of lung function.
Two-dimensional images of the
spine, such as the Cobb angle, do
not correlate with lung function
measures and do not reflect changes
in lung function after spine curvature
has been reduced.61 However,
an encouraging study recently
demonstrated that radiographic
T1 to T12 height and T1 ro S1
height modestly correlate with
improved pulmonary function in
EOS.62 New imaging modalities,
such as diaphragm and thoracic
excursion, measured by dynamic
MRI, hold some promise in improving
assessment of spine structure–
respiratory function relations.
Persistent barriers to a high-quality
literature on the topic include a
lack of control groups, because
untreated progressive EOS is known
to have a poor outcome, and a lack
of standardization and difficulty in
evaluating respiratory function in
young children.
CURRENT TREATMENT RECOMMENDATIONS
Management of EOS involves a
diverse patient population, variable
spinal and thoracic deformities, and
multiple treatment options (Table
2). Optimizing the treatment of each
child is a process in evolution. In
many cases, a trial of serial casting
can help control the scoliosis and
allow growth while delaying surgery.
In some idiopathic cases, these
curves may resolve with casting
alone. Many children may not be able
to tolerate casting or demonstrate
progression of the scoliosis despite
casting necessitating the initiation
of growth-friendly spinal surgery.
There is considerable variation
with regard to the optimal timing
and indication of surgery. A recent
survey of 14 pediatric spine surgeons
found that the majority considered
curves with recent progression and
a magnitude of ≥60° an indication
for distraction-based implants.63 The
indications for any of the distraction-
based implants are similar, although
VEPTR has potential advantages in
cases that require direct expansion
of the thorax, such as cases of
thoracic dystrophy. Compression-
based therapies need more data in
the treatment of EOS, although they
appear to be an option in children
9
FIGURE 11A, Preoperative posteroanterior radiograph of a 7-year-old boy with a 61° curve. B, Initial postoperative radiograph shows correction with a Shilla construct with a fusion at the apex (red arrows) and screws at the upper and lower anchors that can slide along the rod (yellow arrows). C, Images 2.5 years later show how the child’s growth has been guided by the rods, as demonstrated by the shorter distance beyond the anchors that the rods extend (blue arrow). Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
TABLE 2 Summary of Treatment Types for EOS and Some of Their Advantages and Disadvantages
Treatment Pros Cons
Bracing May help delay need for surgery in very
young patients.
Standard thoracolumbosacral orthosis
brace cannot control curves with apex
above midthoracic spine (around T7).
Helpful for idiopathic EOS curves in
juvenile patients near adolescent age.
Brace wear compliance may be diffi cult.
Not much literature about bracing in EOS.
Casting Maximizes spinal growth before surgery. Some children may not tolerate full-time
body cast well.
Some idiopathic curves may resolve. Is not a defi nitive treatment in most cases.
Distraction Effective method to correct curve and
lengthen the spine before fi nal spinal
fusion.
Requires multiple periodic lengthening
surgeries (exception: magnetically
controlled rods).
Holds the most clinical experience and
literature in the surgical treatment of
EOS.
High complication rates (eg, implant failure,
infection).
Guided growth Initial apical fusion procedure guides
subsequent spinal growth.
Requires larger anatomy to allow
instrumentation of apex (avoid in very small
children).
No scheduled repeated lengthening
procedures.
Compression Fusionless procedure. Limited data for use in EOS.
Requires a thoracic approach (potentially
detrimental to pulmonary function).
Risk of overcorrection when used for young
children.
Reproduced with permission of Children’s Orthopedic Center, Los Angeles, California.
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REFERENCES
1. Akbarnia BA, El-Hawary R. Letter
to the editor, early onset scoliosis:
time for consensus. Spine Deform.
2015;3(2):105–106
2. Skaggs DL, Guillaume T, El-Hawary
R, et al. Early onset scoliosis
consensus statement, SRS Growing
Spine Committee. Spine Deform.
2015;3(2):107
3. Williams BA, Matsumoto H, McCalla DJ,
et al. Development and initial validation
of the classifi cation of early-onset
scoliosis (C-EOS). J Bone Joint Surg
Am. 2014;96(16):1359–1367
4. Riseborough EJ, Wynne-Davies R. A
genetic survey of idiopathic scoliosis
in Boston, Massachusetts. J Bone Joint
Surg Am. 1973;55(5):974–982
5. Lloyd-Roberts GC, Pilcher MF.
Structural idiopathic scoliosis in
infancy: a study of the natural history
YANG et al
nearing adolescence, with less total
growth remaining. After achieving
maximal correction and growth with
growth-friendly spinal implants,
children can have their spine
definitively fused at a later age if
significant deformity remains.
FUTURE DIRECTIONS IN EARLY-ONSET SCOLIOSIS
The basic unanswered question is
how much early and late treatment
strategies for EOS maximize
respiratory function when children
reach maturity. This question
remains difficult to study because
it is unethical to have an untreated
natural history comparison group
in which the scoliosis is allowed to
progress relentlessly. Collaboration
between pediatric pulmonologists
and orthopaedists is essential to
standardize how pulmonary function
evaluations are being performed for
children who are not able to comply
with traditional PFTs.
A better understanding of the
3-dimensional natural growth of
the thorax and how it is affected by
surgical treatment in EOS is crucial.
Distraction-based implants help
decrease the scoliosis, although
how this result correlates with
improved pulmonary function has
not been established. Radiographic
measurements in the 2-dimensional
plane, such as Cobb angles, are
not reliable predictors of severity
of pulmonary disease. Three-
dimensional understanding and
functional imaging of the thorax
warrant additional study to improve
characterization of how the structure
of the thorax relates to function to
predict severity of pulmonary disease
in EOS.
EOS incorporates a multitude of
etiologies and associated diagnoses,
and greater subclassification can
help develop a framework for future
study. Each etiology carries different
implications, because congenital and
idiopathic EOS may behave much
differently with regard to the rate
of curve progression. Williams et
al3 developed a new classification
scheme in EOS that may help
establish the optimal treatment of
each subtype of EOS. Multicenter
groups such as the Growing Spine
Study Group and the Chest Wall
and Spine Deformity Study Group
have been developed to collaborate
in the study of this heterogeneous
population of children.
10
ABBREVIATIONS
EOS: early-onset scoliosis
FVC: forced vital capacity
MCGR: magnetically controlled
growing rod
PFT: pulmonary function test
TGR: traditional growing rod
TIS: thoracic insufficiency
syndrome
VEPTR: vertical expandable
prosthetic titanium rib
DOI: 10.1542/peds.2015-0709
Accepted for publication Jul 28, 2015
Address correspondence to David L. Skaggs, MD, MMM, Children’s Orthopaedic Center, Children’s Hospital Los Angeles, 4650 Sunset Blvd, MS#69, Los Angeles, CA
90027. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: Dr Andras owns stock in Eli Lily, receives publishing royalties from Orthobullets, and is a board or committee member of
the Pediatric Orthopaedic Society of North America and the Scoliosis Research Society. Dr Skaggs has received grants from the Pediatric Orthopaedic Society
of North America & Scoliosis Research Society, paid to Columbia University; has received consulting fees or honoraria from Biomet, Medtronic, Zipline Medical,
Inc, and Orthobullets; is a board member of the Growing Spine Study Group, Scoliosis Research Society, and Growing Spine Foundation; has received payment
for lectures including service on speakers’ bureaus from Biomet, Medtronic, and Johnson & Johnson; is a patent holder for Medtronic and Biomet; has
received royalties from Wolters Kluwer Health–Lippincott Williams & Wilkins and Biomet Spine; and has received payment for the development of educational
presentations from Stryker, Biomet, Medtronic, and Johnson & Johnson. Drs Yang and Redding have indicated they have no potential confl icts of interest to
disclose.
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PEDIATRICS Volume 137 , number 1 , January 2016 11
of 100 patients. J Bone Joint Surg Br.
1965;47:520–523
6. Ceballos T, Ferrer-Torrelles M, Castillo
F, Fernandez-Paredes E. Prognosis in
infantile idiopathic scoliosis. J Bone
Joint Surg Am. 1980;62(6):863–875
7. Canavese F, Dimeglio A. Normal
and abnormal spine and thoracic
cage development. World J Orthop.
2013;4(4):167–174
8. Dimeglio A. Growth of the spine before
age 5 years. J Pediatr Orthop B.
1992;1(2):102–107
9. Dimeglio A, Canavese F. The growing
spine: how spinal deformities
infl uence normal spine and
thoracic cage growth. Eur Spine J.
2012;21(1):64–70
10. Dunnill MS. Postnatal growth of the
lung. Thorax. 1962;17(4):329–333
11. Herring MJ, Putney LF, Wyatt G,
Finkbeiner WE, Hyde DM. Growth of
alveoli during postnatal development
in humans based on stereological
estimation. Am J Physiol Lung Cell Mol
Physiol. 2014;307(4):L338–L344
12. Thurlbeck WM. Postnatal human
lung growth. Thorax. 1982;37(8):
564–571
13. Olson JC, Kurek KC, Mehta HP,
Warman ML, Snyder BD. Expansion
thoracoplasty affects lung growth
and morphology in a rabbit model:
a pilot study. Clin Orthop Relat Res.
2011;469(5):1375–1382
14. Davies G, Reid L. Effect of scoliosis
on growth of alveoli and pulmonary
arteries and on right ventricle. Arch
Dis Child. 1971;46(249):623–632
15. Redding GJ. Primary thoraco-spinal
disorders of childhood. Paediatr
Respir Rev. 2015;16(1):25–29. Available
at: www. sciencedirect. com/ science/
article/ pii/ S1526054214001341
16. Campbell RM Jr, Smith MD, Mayes TC,
et al. The characteristics of thoracic
insuffi ciency syndrome associated
with fused ribs and congenital
scoliosis. J Bone Joint Surg Am.
2003;85-A(3):399–408
17. Vitale MG, Matsumoto H, Roye DP Jr,
et al. Health-related quality of life in
children with thoracic insuffi ciency
syndrome. J Pediatr Orthop.
2008;28(2):239–243
18. Pehrsson K, Larsson S, Oden A,
Nachemson A. Long-term follow-up
of patients with untreated scoliosis.
A study of mortality, causes of
death, and symptoms. Spine.
1992;17(9):1091–1096
19. Moe JH, Kharrat K, Winter RB, Cummine
JL. Harrington instrumentation without
fusion plus external orthotic support
for the treatment of diffi cult curvature
problems in young children. Clin
Orthop Relat Res. May 1984;185:35–45
20. Goldberg CJ, Gillic I, Connaughton O, et
al. Respiratory function and cosmesis
at maturity in infantile-onset scoliosis.
Spine. 2003;28(20):2397–2406
21. 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(6):1272–1281
22. Skaggs DL, Akbarnia BA, Flynn JM,
Myung KS, Sponseller PD, Vitale MG;
Chest Wall and Spine Deformity Study
Group; Growing Spine Study Group;
Pediatric Orthopaedic Society of North
America; Scoliosis Research Society
Growing Spine Study Committee.
A classifi cation of growth friendly
spine implants. J Pediatr Orthop.
2014;34(3):260–274
23. Smith JR, Samdani AF, Pahys J, et
al. The role of bracing, casting,
and vertical expandable prosthetic
titanium rib for the treatment of
infantile idiopathic scoliosis: a
single-institution experience with 31
consecutive patients. Clinical article. J
Neurosurg Spine. 2009;11(1):3–8
24. Thompson SK, Bentley G. Prognosis in
infantile idiopathic scoliosis. J Bone
Joint Surg Br. 1980;62-B(2):151–154
25. Mehta MH. Growth as a corrective
force in the early treatment of
progressive infantile scoliosis. J Bone
Joint Surg Br. 2005;87(9):1237–1247
26. Demirkiran HG, Bekmez S, Celilov
R, Ayvaz M, Dede O, Yazici M. Serial
derotational casting in congenital
scoliosis as a time-buying strategy. J
Pediatr Orthop. 2015;35(1)▪▪▪:43–49
27. Waldron SR, Poe-Kochert C, Son-Hing
JP, Thompson GH. Early onset scoliosis:
the value of serial Risser casts. J
Pediatr Orthop. 2013;33(8):775–780
28. Baulesh DM, Huh J, Judkins T, Garg
S, Miller NH, Erickson MA. The role
of serial casting in early-onset
scoliosis (EOS). J Pediatr Orthop.
2012;32(7):658–663
29. Akbarnia BA, Marks DS, Boachie-
Adjei O, Thompson AG, Asher MA.
Dual growing rod technique for
the treatment of progressive early-
onset scoliosis: a multicenter study.
Spine (Phila Pa 1976). 2005;30(17
suppl):S46–57
30. Akbarnia BA, Breakwell LM, Marks DS,
et al; Growing Spine Study Group. Dual
growing rod technique followed for
three to eleven years until fi nal fusion:
the effect of frequency of lengthening.
Spine. 2008;33(9):984–990
31. Schulz JF, Smith J, Cahill PJ, Fine A,
Samdani AF. The role of the vertical
expandable titanium rib in the
treatment of infantile idiopathic
scoliosis: early results from a
single institution. J Pediatr Orthop.
2010;30(7):659–663
32. Hasler CC, Mehrkens A, Hefti F. Effi cacy
and safety of VEPTR instrumentation
for progressive spine deformities in
young children without rib fusions. Eur
Spine J. 2010;19(3):400–408
33. Yamaguchi KT Jr, Skaggs DL, Mansour
S, et al. Are rib versus spine anchors
protective against breakage of
growing rods? Spine Deform.
2014;2(6):489–492
34. Dannawi Z, Altaf F, Harshavardhana NS,
El Sebaie H, Noordeen H. Early results
of a remotely-operated magnetic
growth rod in early-onset scoliosis.
Bone Joint J. 2013;95-B(1):75–80
35. Akbarnia BA, Cheung K, Noordeen H,
et al. Next generation of growth-
sparing techniques: preliminary
clinical results of a magnetically
controlled growing rod in 14 patients
with early-onset scoliosis. Spine.
2013;38(8):665–670
36. Hickey BA, Towriss C, Baxter G, et al.
Early experience of MAGEC magnetic
growing rods in the treatment of
early onset scoliosis. Eur Spine J.
2014;23(suppl 1):S61–S65
37. Akbarnia BA, Pawelek JB, Cheung KMC,
et al. Traditional growing rods versus
magnetically controlled growing
rods for the surgical treatment
by guest on January 1, 2020www.aappublications.org/newsDownloaded from
YANG et al 12
of early-onset scoliosis: a case-
matched 2-year study. Spine Deform.
2014;2(6):493–497
38. Bess S, Akbarnia BA, Thompson GH,
et al. Complications of growing-rod
treatment for early-onset scoliosis:
analysis of one hundred and forty
patients. J Bone Joint Surg Am.
2010;92(15):2533–2543
39. Flynn JM, Tomlinson LA, Pawelek J,
Thompson GH, McCarthy R, Akbarnia
BA; Growing Spine Study Group.
Growing-rod graduates: lessons
learned from ninety-nine patients who
completed lengthening. J Bone Joint
Surg Am. 2013;95(19):1745–1750
40. Watanabe K, Uno K, Suzuki T, et
al. Risk factors for complications
associated with growing-rod surgery
for early-onset scoliosis. Spine.
2013;38(8):e464–e468
41. Kabirian N, Akbarnia BA, Pawelek JB, et
al Deep surgical site infection following
2344 growing-rod procedures for
early-onset scoliosis: Risk factors and
clinical consequences. J Bone Joint
Surg Am. 2014;96(15):e128
42. Matsumoto H, Williams BA, Corona J,
et al. Psychosocial effects of repetitive
surgeries in children with early-onset
scoliosis: are we putting them at risk?
J Pediatr Orthop. 2014;34(2):172–178
43. Sankar WN, Acevedo DC, Skaggs DL.
Comparison of complications among
growing spinal implants. Spine.
2010;35(23):2091–2096
44. Smith JT, Johnston C, Skaggs D, Flynn J,
Vitale M. A new classifi cation system to
report complications in growing spine
surgery: a multicenter consensus
study [published online ahead of print
January 8, 2015]. J Pediatr Orthop.
10.1097/BPO.0000000000000386
45. Sankar WN, Skaggs DL, Yazici M, et al.
Lengthening of dual growing rods and
the law of diminishing returns. Spine.
2011;36(10):806–809
46. Noordeen HM, Shah SA, Elsebaie
HB, Garrido E, Farooq N, Al-Mukhtar
M. In vivo distraction force and
length measurements of growing
rods: which factors infl uence the
ability to lengthen? [published
correction appears in Spine (Phila
Pa 1976). 2012;37(5):432]. Spine.
2011;36(26):2299–2303
47. Cahill PJ, Marvil S, Cuddihy L, et al.
Autofusion in the immature spine
treated with growing rods. Spine.
2010;35(22):e1199–e1203
48. Loepke AW, Soriano SG. An assessment
of the effects of general anesthetics
on developing brain structure and
neurocognitive function. Anesth Analg.
2008;106(6):1681–1707
49. Lee JH, Zhang J, Wei L, Yu SP.
Neurodevelopmental implications of
the general anesthesia in neonate
and infants [published online ahead
of print April 8, 2015]. Exp Neurol.
10.1016/j.expneurol.2015.03.028
50. McCann ME, Soriano SG. General
anesthetics in pediatric anesthesia:
infl uences on the developing brain.
Curr Drug Targets. 2012;13(7):944–951
51. Andras LM, Joiner ER, McCarthy
RE, et al. Growing rods vs. Shilla
growth guidance: better Cobb angle
correction and T1–S1 length increase
but more surgeries. Spine Deform.
2015;3(3):246–252
52. Betz RR, Ranade A, Samdani AF, et al.
Vertebral body stapling: a fusionless
treatment option for a growing child
with moderate idiopathic scoliosis.
Spine. 2010;35(2):169–176
53. Crawford CH III, Lenke LG. Growth
modulation by means of anterior
tethering resulting in progressive
correction of juvenile idiopathic
scoliosis: a case report. J Bone Joint
Surg Am. 2010;92(1):202–209
54. Lonner BS, Auerbach JD, Estreicher
MB, et al. Pulmonary function changes
after various anterior approaches in
the treatment of adolescent idiopathic
scoliosis. J Spinal Disord Tech.
2009;22(8):551–558
55. Motoyama EK, Deeney VF, Fine GF,
et al. Effects on lung function of
multiple expansion thoracoplasty in
children with thoracic insuffi ciency
syndrome: a longitudinal study. Spine.
2006;31(3):284–290
56. Mayer OH, Redding G. Early changes
in pulmonary function after vertical
expandable prosthetic titanium rib
insertion in children with thoracic
insuffi ciency syndrome. J Pediatr
Orthop. 2009;29(1):35–38
57. Dede O, Motoyama EK, Yang CI, et al
Pulmonary and radiographic outcomes
of VEPTR (vertical expandable
prosthetic titanium rib) treatment in
early-onset scoliosis. J Bone Joint Surg
Am. 2014;96(15):1295–1302
58. Skaggs DL, Sankar WN, Albrektson
J, Wren TA, Campbell RM. Weight
gain following vertical expandable
prosthetic titanium ribs surgery
in children with thoracic
insuffi ciency syndrome. Spine.
2009;34(23):2530–2533
59. Myung KS, Skaggs DL, Thompson GH,
Emans JB, Akbarnia BA; Growing
Spine Study Group. Nutritional
improvement following growing
rod surgery in children with early
onset scoliosis. J Child Orthop.
2014;8(3):251–256
60. Striegl A, Chen ML, Kifl e Y, Song K,
Redding G. Sleep-disordered breathing
in children with thoracic insuffi ciency
syndrome. Pediatr Pulmonol.
2010;45(5):469–474
61. Redding GJ, Mayer OH. Structure-
respiration function relationships
before and after surgical treatment of
early-onset scoliosis. Clin Orthop Relat
Res. 2011;469(5):1330–1334
62. Glotzbecker M, Johnston C, Miller P,
et al. Is there a relationship between
thoracic dimensions and pulmonary
function in early-onset scoliosis?
Spine. 2014;39(19):1590–1595
63. Corona J, Miller DJ, Downs J, et
al. Evaluating the extent of clinical
uncertainty among treatment options
for patients with early-onset scoliosis.
J Bone Joint Surg Am. 2013;95(10):e67
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Early-Onset Scoliosis: A Review of History, Current Treatment, and Future
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