Recent advances in the treatment of scoliosis in children Focus On Genetics

Transcription

Recent advances in the treatment of scoliosis in children Focus On Genetics
Focus On
Recent advances in the
treatment of scoliosis in children
Genetics
Adolescent idiopathic scoliosis (AIS) has been shown in both
clinical and genetic studies to have a genetic component to its
aetiology,1-8 although the pattern of inheritance still remains elusive; X-linked dominant,3 autosomal dominant or multifactorial
patterns1,2,7 have all been suggested. Genealogy work with a
cohort of 145 patients with AIS demonstrated a 97% connectedness to other families with AIS, with differences in both expressivity and penetrance, suggesting that there is more than one
gene responsible for AIS.9 Work using genome-wide scanning
continues to support this hypothesis by identifying specific areas
on the human genome which are potentially significant in the
aetiology.7 Miller et al,6 in one study of 1198 individuals in 202
families, reported linkage to loci on chromosomes 6p, 6q, 9q,
16q, 17p and 17q. This followed work by Wise et al,10 who identified loci on chromosomes 6p, 10q and 18q in one polygeneration family and Chan et al,11 who reported loci on chromosomes
19p and 2q.
Predicting the risk of curve progression has also been the
focus of genome studies. Braun et al12 identified 12 DNA markers as having diagnostic utility in AIS. When compared with
standard radiological methods, these markers provided a superior assessment of risk of progression. Further development of
this work has led to the ‘Scoliscore AIS prognostic test’ becoming
available to spine specialists in the US in 2009.13 This salivabased genetic test uses 53 DNA markers which have been linked
to the progressive form of scoliosis. Validation work by the development company, Axial Biotech, quotes a 99% negative predictive value (95% confidence interval (CI) 96% to 100%) but
independent validation is awaited.
Bracing
The use of orthotics to treat AIS is a time-honoured tradition in
countries around the world.14 Despite bracing being the mainstay of conservative treatment, its efficacy has not been demonstrated definitively in prospective or randomised clinical
studies.15 It is possible to find support in the literature on the
effectiveness of braces in preventing curve progression.16-20
This support includes the Scoliosis Research Society brace
study, which is the only prospective, multicentre controlled
study so far reported, that compares bracing with observation
and concluded that bracing was more effective than observation alone21,22 but it must be noted that this study “was nonrandomised, non-blinded, the baseline differences between
the groups were not statistically adjusted for and the results
did not include the surgical rates”.14 A meta-analysis performed in 199715 also supported the use of brace treatment
and advocated a 23-hour regimen. This was shown to be significantly more effective than any other form of conservative
treatment, including regimens that involved fewer hours per
day in the brace. Conversely, there are multiple studies which
have concluded that bracing is ineffective in preventing curve
progression,23-25 including a review article in 199926 which
critically deconstructs the results and conclusions of previous
papers which support bracing, while advocating a watchful
waiting policy. A more recent systematic review of the relevant
clinical studies aimed to identify a pooled estimate of the incidence of surgery in patients who had been treated by observation only (three studies, 139 patients) and for those treated in
a brace (15 studies, 1814 patients). The pooled surgical rate
was 23% (95% CI 20% to 24%) after bracing and 22% (95% CI
16% to 29%) after observation leading to the conclusion that
there was no evidence to recommend bracing rather than
observation.27
Compliance with brace use has always been a major problem,
with most regimens being intensive in terms of time, social
acceptance and limitations in physical activity. By designing a discrete choice experiment28 it was shown that patients with scoliosis would be prepared to undergo brace treatment only if it were to
provide a sizeable reduction in the risk of surgery. Effectiveness
and discomfort in wearing a brace were the most important determinants of choice. The issue of brace efficacy is thus far from
resolved. In an attempt to improve brace comfort and, therefore,
compliance, there has been work undertaken on flexible spinal
orthoses.29 However, as yet these have not proven to be better
than rigid orthoses in either efficacy or patient acceptance.30
It appears that there are many issues in respect of the brace
treatment of AIS that have yet to be resolved. In order to help clinicians, patients and parents make a more informed choice
about brace treatment, better quality prospective studies are
needed. Some key issues may be answered in the Bracing in
Adolescent Idiopathic Scoliosis Trial (BrAIST), a 27-centre randomised, controlled trial currently undergoing its second year of
recruitment.31 This trial aims to randomise patients at high risk
of curve progression into either a group treated with a thoracolumbar spinal orthosis or a group treated by observation alone,
and will compare clinical, radiographic and psychosocial
outcomes.
©2011 British Editorial Society of Bone and Joint Surgery
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M. STENNING, I. NELSON
Instrumentation and fusion
The instrumentation technique used to supplement fusion in
surgery for AIS is constantly evolving. Harrington's spinal instrumentation system32 gave improved curve correction and allowed
early mobilisation in a brace rather than a bulky cast. Luque
introduced the principles of segmental instrumentation and correction via translation and derotation by using sublaminar
wires.33 With the advent of Cotrel-Dubousset implants34 these
concepts have been expanded to include hook, hybrid and most
recently, all-screw constructs.35 In the last decade in particular,
increased attention has been paid to re-establish normal sagittal balance during the surgical correction of scoliosis.
All-screw constructs have become the gold standard instrumentation technique for thoracic AIS. A pedicle screw achieves
three-column fixation of the vertebral body35 and displays biomechanical properties that are superior to other forms of construct.36-38 This allows the surgeon to achieve greater correction
of the curve in all three planes, including rotation, with relatively
simple rod derotation manoeuvres; this was a failing of techniques that used hooks. There is also less canal intrusion and
risk of dislodgement or migration into the canal when compared
with hook fixation.35 Coronal correction of the curve by up to
70% has been reported with all-screw constructs, hook fixation
achieving less than 50%.35,39-42 Better correction of the reduced
thoracic kyphosis seen in AIS has also been reported with the
use of an all-screw technique,34,42 although some have noted a
tendency for all-screw constructs to cause flattening of the thoracic spine during the correction,35,43 which occurred when rods
of inadequate thickness were used .
Before the introduction of all-screw constructs, the more
severe thoracic AIS curves (Cobb angle > 60°) required a combined anterior and posterior fusion in order to improve the coronal correction and fusion rates. The deterioration in pulmonary
function with a thoracotomy in these cases is well documented.44,45 A posterior spinal fusion using an all-screw construct has been shown to provide an equivalent degree of curve
correction compared with the combined approach in patients
with a curve of 70° to 100°, negating the need for thoracotomy
in these patients.45
Pedicle screws are not only effective but have also been
shown to be safe in all types of curve. This was an initial concern
for many surgeons with their use in the thoracic spine. Three
recent, large studies have demonstrated the complication rates
of using pedicle screws in AIS. Neurological injuries have been
reported in 0% to 1.5% of patients, with all deficits being transient.35,46,47 Screw malposition is said to be 1.5% when
assessed by plain radiography47 and 6% when assessed by finecut CT scans; however, these patients were asymptomatic and
did not require screw revision anyway.46 A pedicle fracture rate of
0.24% was seen, with one patient out of 462 requiring revision
surgery; intraoperative screw loosening was noted in 0.76% of
patients.47 Peri-operative pulmonary function has also been
shown to improve in patients after all-screw constructs when
compared with hook systems. This is thought to be because of
improved alignment of the chest wall with all-screw
constructs.35,41
The use of all-screw constructs has been extended from AIS to
adult idiopathic scoliosis. Adult curves are stiffer and have a
higher rate of pseudarthrosis when compared with their adolescent counterparts.48,49 Hook-based constructs are less likely to
provide adequate curve correction and this can lead to an
increased need for combined anterior and posterior surgery. The
improved biomechanical profile of all-screw constructs results in
improved curve correction while avoiding the morbidity of anterior surgery; in one study this conferred a significantly lower complication rate.50 Re-establishment of normal sagittal balance is
particularly important in the adult and may necessitate spinal
osteotomies such as the chevron or Ponte, pedicle subtraction
osteotomy or vertebral column resection.
Surgical treatment of early onset scoliosis
Patients with AIS typically present at a stage in their development where the thorax has achieved most of its adult volume
and has near-normal vital capacity. Surgical treatment involves
definitive spinal fusion and has a negligible effect on thoracic
growth or long-term pulmonary outcome. Early-onset scoliosis,
irrespective of cause (congenital, neuromuscular, etc.)
presents the surgeon with a different set of challenges. Spinal
lordosis and curve rotation leaves the thorax with a volumedepletion deformity and growth inhibition ultimately leading to
Thoracic Insufficiency Syndrome (TIS). This is defined as “the
inability of the thorax to support normal respiration or lung
growth”.51 Associated abnormalities of the rib cage can add to
the thoracic disability. Standard surgical treatment of scoliosis
is often not possible in these cases because of the detrimental
effect that spinal fusion might have on spinal and thoracic
growth.52
The goal of surgical treatment in early-onset scoliosis is “to
stop the progression of the curve whilst allowing maximum
growth of the spine, lungs and thoracic cage”.53 In order to
achieve this a number of different surgical approaches can be
employed.
Posterior instrumentation without fusion, using dual growing
rods, is used when the primary problem is at the vertebral column.54 The dual rod technique has been shown to give significantly better correction of the scoliosis when compared with
single rod techniques.55 Subperiosteal dissection and fusion is
performed only at the upper and lower anchor sites of the construct. Each rod is then measured, contoured and cut into an
upper and lower portion. A connector, usually placed at the thoracolumbar junction, links the upper and lower rods on either
side of the spine.53 The best time between lengthening procedures is about six months, with longer intervals leading to less
spinal growth and poorer correction of the scoliosis.56 The
results of dual growing rods in 23 patients with minimum of two
years' follow-up have been presented by the Growing Spine
Study Group (GSSG).57 These patients, with a mean age of
5.4 years at first surgery, required a mean of 6.6 lengthening
procedures. The Cobb angle was reduced from a mean of 82°
before surgery to 36° at the end of treatment. Meanwhile, the
mean spinal growth was 1.21 cm per year, which approaches
that associated with normal spinal growth.53
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RECENT ADVANCES IN THE TREATMENT OF SCOLIOSIS IN CHILDREN
When the primary problem involves the thoracic cage, for
example TIS has developed or the patient has rib fusions, reconstruction of the thoracic cage needs to be considered. Expansion
thoracoplasty and insertion of a vertical expandable prosthetic
titanium rib (VEPTR) has been developed to treat such cases.58
This technique addresses all related components of the thoracic
deformity in the growing child, including the spine, rib cage and
diaphragm, without compromising thoracic growth.55 Rather
than directly correcting the spinal deformity with instrumentation, this technique involves correcting the thoracic deformity
with rib osteotomies or intercostal muscle lysis. This enlarges
the constricted thorax which is then maintained by insertion of
the VEPTR device. As with the growing rods, lengthening is
required approximately every six months.
Growth of the spine in cases where the VEPTR technique has
been used is nearly normal.59,60 Improvement in thoracic constriction and lung function has been difficult to confirm because
of the problems in measuring pulmonary function in young children; however, some studies have shown a decreased ventilator
dependence and increases in thoracic and lung volumes.58-63
The interpretation of these results must be guarded as all of the
studies are non-randomised case series without controls.54
The surgical treatment of progressive, early-onset scoliosis is
complex and associated with a high complication rate. A 48%
complication rate during treatment was quoted in a GSSG followup of 23 patients who had received dual growing rods; four
patients (17%) had required unplanned procedures for infection.
Implant problems, such as rod breakage, hook dislodgement
and screw pull-out, were all addressed during planned lengthening as were two alignment problems (one crankshaft phenomenon and one junctional kyphosis.57 A further study in
48 patients, also by the GSSG, identified 55 complications in
29 patients, with 23 patients requiring unplanned procedures.64
Again, wound problems were the most common cause of
unplanned procedures while most implant problems could be
addressed during a planned procedure. This study also noted
that younger patients had higher complication rates and the
complications changed from wound problems to implant problems as the interval between lengthening procedures increased.
The VEPTR devices are less likely to break when compared
with growing rods. Meanwhile, spontaneous spinal fusion adjacent to the device is uncommon but infection and soft-tissue
scarring are common, while drifting of the rib and spinal anchor
points can occur. With repetitive lengthening the expansion portion of the device can be outgrown and requires exchanging,
which is a more extensive procedure compared with simple
lengthening.54
Mr M Stenning MBBS, MPhil, FRCS (Tr & Orth)
Mr I Nelson MBBS, MChOrth, FRCS.
Department of Orthopaedic Spine Surgery
North Bristol NHS Trust
Frenchay Hospital
Bristol BS16 1LE
Email: [email protected]
3
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THE JOURNAL OF BONE AND JOINT SURGERY