Focus On Recent advances in the treatment of scoliosis in children

Genetics the groups were not statistically adjusted for and the results Adolescent idiopathic scoliosis (AIS) has been shown in both did not include the surgical rates”.14 A meta-analysis per- clinical and genetic studies to have a genetic component to its formed in 199715 also supported the use of brace treatment aetiology,1-8 although the pattern of inheritance still remains elu- and advocated a 23-hour regimen. This was shown to be signif- sive; X-linked dominant,3 autosomal dominant or multifactorial icantly more effective than any other form of conservative patterns1,2,7 have all been suggested. Genealogy work with a treatment, including regimens that involved fewer hours per cohort of 145 patients with AIS demonstrated a 97% connected- day in the brace. Conversely, there are multiple studies which ness to other families with AIS, with differences in both expres- have concluded that bracing is ineffective in preventing curve sivity and penetrance, suggesting that there is more than one progression,23-25 including a review article in 199926 which gene responsible for AIS.9 Work using genome-wide scanning critically deconstructs the results and conclusions of previous continues to support this hypothesis by identifying specific areas papers which support bracing, while advocating a watchful on the human genome which are potentially significant in the waiting policy. A more recent systematic review of the relevant aetiology.7 Miller et al,6 in one study of 1198 individuals in 202 clinical studies aimed to identify a pooled estimate of the inci- families, reported linkage to loci on chromosomes 6p, 6q, 9q, dence of surgery in patients who had been treated by observa- 16q, 17p and 17q. This followed work by Wise et al,10 who iden- tion only (three studies, 139 patients) and for those treated in tified loci on chromosomes 6p, 10q and 18q in one polygenera- a brace (15 studies, 1814 patients). The pooled surgical rate tion family and Chan et al,11 who reported loci on chromosomes was 23% (95% CI 20% to 24%) after bracing and 22% (95% CI 19p and 2q. 16% to 29%) after observation leading to the conclusion that Predicting the risk of curve progression has also been the there was no evidence to recommend bracing rather than focus of genome studies. Braun et al12 identified 12 DNA mark- observation.27 ers as having diagnostic utility in AIS. When compared with Compliance with brace use has always been a major problem, standard radiological methods, these markers provided a supe- with most regimens being intensive in terms of time, social rior assessment of risk of progression. Further development of acceptance and limitations in physical activity. By designing a dis- this work has led to the ‘Scoliscore AIS prognostic test’ becoming crete choice experiment28 it was shown that patients with scolio- available to spine specialists in the US in 2009.13 This saliva- sis would be prepared to undergo brace treatment only if it were to based genetic test uses 53 DNA markers which have been linked provide a sizeable reduction in the risk of surgery. Effectiveness to the progressive form of scoliosis. Validation work by the devel- and discomfort in wearing a brace were the most important deter- opment company, Axial Biotech, quotes a 99% negative predic- minants of choice. The issue of brace efficacy is thus far from tive value (95% confidence interval (CI) 96% to 100%) but resolved. In an attempt to improve brace comfort and, therefore, independent validation is awaited. compliance, there has been work undertaken on flexible spinal orthoses.29 However, as yet these have not proven to be better Bracing than rigid orthoses in either efficacy or patient acceptance.30 The use of orthotics to treat AIS is a time-honoured tradition in It appears that there are many issues in respect of the brace countries around the world.14 Despite bracing being the main- treatment of AIS that have yet to be resolved. In order to help cli- stay of conservative treatment, its efficacy has not been dem- nicians, patients and parents make a more informed choice onstrated definitively in prospective or randomised clinical about brace treatment, better quality prospective studies are studies.15 It is possible to find support in the literature on the needed. Some key issues may be answered in the Bracing in effectiveness of braces in preventing curve progression.16-20 Adolescent Idiopathic Scoliosis Trial (BrAIST), a 27-centre ran- This support includes the Scoliosis Research Society brace domised, controlled trial currently undergoing its second year of study, which is the only prospective, multicentre controlled recruitment.31 This trial aims to randomise patients at high risk study so far reported, that compares bracing with observation of curve progression into either a group treated with a thoraco- and concluded that bracing was more effective than observa- lumbar spinal orthosis or a group treated by observation alone, tion alone21,22 but it must be noted that this study “was non- and will compare clinical, radiographic and psychosocial randomised, non-blinded, the baseline differences between outcomes.

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1 2 M. STENNING, I. NELSON

Instrumentation and fusion The use of all-screw constructs has been extended from AIS to The instrumentation technique used to supplement fusion in adult idiopathic scoliosis. Adult curves are stiffer and have a surgery for AIS is constantly evolving. Harrington's spinal instru- higher rate of pseudarthrosis when compared with their adoles- mentation system32 gave improved curve correction and allowed cent counterparts.48,49 Hook-based constructs are less likely to early mobilisation in a brace rather than a bulky cast. Luque provide adequate curve correction and this can lead to an introduced the principles of segmental instrumentation and cor- increased need for combined anterior and posterior surgery. The rection via translation and derotation by using sublaminar improved biomechanical profile of all-screw constructs results in wires.33 With the advent of Cotrel-Dubousset implants34 these improved curve correction while avoiding the morbidity of ante- concepts have been expanded to include hook, hybrid and most rior surgery; in one study this conferred a significantly lower com- recently, all-screw constructs.35 In the last decade in particular, plication rate.50 Re-establishment of normal sagittal balance is increased attention has been paid to re-establish normal sagit- particularly important in the adult and may necessitate spinal tal balance during the surgical correction of scoliosis. osteotomies such as the chevron or Ponte, pedicle subtraction All-screw constructs have become the gold standard instru- osteotomy or vertebral column resection. mentation technique for thoracic AIS. A pedicle screw achieves three-column fixation of the vertebral body35 and displays bio- Surgical treatment of early onset scoliosis mechanical properties that are superior to other forms of con- Patients with AIS typically present at a stage in their develop- struct.36-38 This allows the surgeon to achieve greater correction ment where the thorax has achieved most of its adult volume of the curve in all three planes, including rotation, with relatively and has near-normal vital capacity. Surgical treatment involves simple rod derotation manoeuvres; this was a failing of tech- definitive spinal fusion and has a negligible effect on thoracic niques that used hooks. There is also less canal intrusion and growth or long-term pulmonary outcome. Early-onset scoliosis, risk of dislodgement or migration into the canal when compared irrespective of cause (congenital, neuromuscular, etc.) with hook fixation.35 Coronal correction of the curve by up to presents the surgeon with a different set of challenges. Spinal 70% has been reported with all-screw constructs, hook fixation lordosis and curve rotation leaves the thorax with a volume- achieving less than 50%.35,39-42 Better correction of the reduced depletion deformity and growth inhibition ultimately leading to thoracic kyphosis seen in AIS has also been reported with the Thoracic Insufficiency Syndrome (TIS). This is defined as “the use of an all-screw technique,34,42 although some have noted a inability of the thorax to support normal respiration or lung tendency for all-screw constructs to cause flattening of the tho- growth”.51 Associated abnormalities of the rib cage can add to racic spine during the correction,35,43 which occurred when rods the thoracic disability. Standard surgical treatment of scoliosis of inadequate thickness were used . is often not possible in these cases because of the detrimental Before the introduction of all-screw constructs, the more effect that spinal fusion might have on spinal and thoracic severe thoracic AIS curves (Cobb angle > 60°) required a com- growth.52 bined anterior and posterior fusion in order to improve the coro- The goal of surgical treatment in early-onset scoliosis is “to nal correction and fusion rates. The deterioration in pulmonary stop the progression of the curve whilst allowing maximum function with a thoracotomy in these cases is well docu- growth of the spine, lungs and thoracic cage”.53 In order to mented.44,45 A posterior spinal fusion using an all-screw con- achieve this a number of different surgical approaches can be struct has been shown to provide an equivalent degree of curve employed. correction compared with the combined approach in patients Posterior instrumentation without fusion, using dual growing with a curve of 70° to 100°, negating the need for thoracotomy rods, is used when the primary problem is at the vertebral col- in these patients.45 umn.54 The dual rod technique has been shown to give signifi- Pedicle screws are not only effective but have also been cantly better correction of the scoliosis when compared with shown to be safe in all types of curve. This was an initial concern single rod techniques.55 Subperiosteal dissection and fusion is for many surgeons with their use in the thoracic spine. Three performed only at the upper and lower anchor sites of the con- recent, large studies have demonstrated the complication rates struct. Each rod is then measured, contoured and cut into an of using pedicle screws in AIS. Neurological injuries have been upper and lower portion. A connector, usually placed at the tho- reported in 0% to 1.5% of patients, with all deficits being tran- racolumbar junction, links the upper and lower rods on either sient.35,46,47 Screw malposition is said to be 1.5% when side of the spine.53 The best time between lengthening proce- assessed by plain radiography47 and 6% when assessed by fine- dures is about six months, with longer intervals leading to less cut CT scans; however, these patients were asymptomatic and spinal growth and poorer correction of the scoliosis.56 The did not require screw revision anyway.46 A pedicle fracture rate of results of dual growing rods in 23 patients with minimum of two 0.24% was seen, with one patient out of 462 requiring revision years' follow-up have been presented by the Growing Spine surgery; intraoperative screw loosening was noted in 0.76% of Study Group (GSSG).57 These patients, with a mean age of patients.47 Peri-operative pulmonary function has also been 5.4 years at first surgery, required a mean of 6.6 lengthening shown to improve in patients after all-screw constructs when procedures. The Cobb angle was reduced from a mean of 82° compared with hook systems. This is thought to be because of before surgery to 36° at the end of treatment. Meanwhile, the improved alignment of the chest wall with all-screw mean spinal growth was 1.21 cm per year, which approaches constructs.35,41 that associated with normal spinal growth.53

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When the primary problem involves the thoracic cage, for References example TIS has developed or the patient has rib fusions, recon- 1. Wynne-Davies R. Familial (idiopathic) scoliosis. A family survey. J Bone Joint Surg (Br) struction of the thoracic cage needs to be considered. Expansion 1968;50:24-30. 2. Riseborough EJ, Wynne-Davies R. A genetic survey of idiopathic scoliosis in Boston, thoracoplasty and insertion of a vertical expandable prosthetic Massachusetts. J Bone Joint Surg (Am) 1973;55:974-982. 58 titanium rib (VEPTR) has been developed to treat such cases. 3. Cowell HR, Hall JN, MacEwen GD. Genetic aspects of idiopathic scoliosis. A Nicho- This technique addresses all related components of the thoracic las Andry Award essay, 1970. Clin Orthop Relat Res 1972;86:121-131. deformity in the growing child, including the spine, rib cage and 4. Justice CM, Miller NH, Marosy B, et al. Familial idiopathic scoliosis: evidence of an diaphragm, without compromising thoracic growth.55 Rather X-linked susceptibility locus. Spine 2003;28:589-594. 5. Lowe TG, Edgar M, Margulies JY, et al. Etiology of idiopathic scoliosis: current than directly correcting the spinal deformity with instrumenta- trends in research. J Bone Joint Surg (Am) 2000;82:1157-1168. tion, this technique involves correcting the thoracic deformity 6. Miller NH, Justice CM, Marosy B, et al. Identification of candidate regions for with rib osteotomies or intercostal muscle lysis. This enlarges familial idiopathic scoliosis. Spine 2005;30:1181-1187. the constricted thorax which is then maintained by insertion of 7. Clough M, Justice CM, Marosy B, et al. Males with familial idiopathic scoliosis: a the VEPTR device. As with the growing rods, lengthening is distinct phenotypic subgroup. Spine 2010;35:162-168. 8. Kesling KL, Reinker KA. Scoliosis in twins. A meta-analysis of the literature and required approximately every six months. report of six cases. Spine 1997;22:2009-2014. Growth of the spine in cases where the VEPTR technique has 9. Ogilvie JW, Braun J, Argyle V, et al. The search for idiopathic scoliosis genes. Spine been used is nearly normal.59,60 Improvement in thoracic con- 2006;31:679-681. striction and lung function has been difficult to confirm because 10. Wise CA, Barnes R, Gillum J, et al. Localisation of susceptibility to familial idio- of the problems in measuring pulmonary function in young chil- pathic scoliosis. Spine 2000;25:2372-2380. 11. Chan V, Fong GC, Luk KD, et al. A genetic locus for adolescent idiopathic scoliosis dren; however, some studies have shown a decreased ventilator linked to chromosome 19p13.3. Am J Hum Genet 2002; 1:401-406. 58-63 dependence and increases in thoracic and lung volumes. 12. Braun JT, Nelson L,Ogilvie J, Ward K. Twelve DNA markers accurately assess risk The interpretation of these results must be guarded as all of the of progression in adolescent idiopathic scoliosis. Scoliosis Research Society 42nd studies are non-randomised case series without controls.54 Annual Meeting and Course. Sept 2007, Edin. The surgical treatment of progressive, early-onset scoliosis is 13. www.scoliscore.com Nov 2010 14. Dolan LA, Weinstein SL. Surgical rates after observation and bracing for adolescent complex and associated with a high complication rate. A 48% idiopathic scoliosis. An evidence-based review. Spine 2007;195:S91-100 complication rate during treatment was quoted in a GSSG follow- 15. Rowe DE, Bernstein SM, Riddick MF, et al. A meta-analysis of the efficacy of non- up of 23 patients who had received dual growing rods; four operative treatments for idiopathic scoliosis. J Bone Joint Surg (Am) 1997; 79: 664-674. patients (17%) had required unplanned procedures for infection. 16. Lonstein JE, Winter RB. The Milwaukee brace for the treatment of adolescent idio- pathic scoliosis: a review of one thousand and twenty patients. J Bone Joint Surg (Am) Implant problems, such as rod breakage, hook dislodgement 1994; 76: 1207-1221. and screw pull-out, were all addressed during planned lengthen- 17. Fernandez-Feliberti R, Flynn J, Ramirez N, et al. Effectiveness of TLSO bracing in ing as were two alignment problems (one crankshaft phenome- the conservative treatment of idiopathic scoliosis. J Pediatr Orthop 1995; 15: 176-181. non and one junctional kyphosis.57 A further study in 18. Olafsson Y, Saraste H, Soderland V, et al. Boston brace in the treatment of idio- 48 patients, also by the GSSG, identified 55 complications in pathic scoliosis. J Pediatr Orthop 1995; 15: 524-527. 64 19. D’Amato CR, Griggs S, McCoy B. Night-time bracing with the Providence brace in 29 patients, with 23 patients requiring unplanned procedures. adolescent girls with idiopathic scoliosis. Spine 2001; 26: 2006-2012. Again, wound problems were the most common cause of 20. Gabos PG, Bojescul JA, Bowen JR, et al. Long-term follow-up of female patients unplanned procedures while most implant problems could be with idiopathic scoliosis treated with the Wilmington orthosis. J Bone Joint Surg (Am) addressed during a planned procedure. This study also noted 2004; 86:1891-1899. 21. Peterson LE, Nachemson AL. Prediction of progression of the curve in girls who have that younger patients had higher complication rates and the adolescent idiopathic scoliosis of moderate severity: logistic regression analysis based complications changed from wound problems to implant prob- on data from the Brace Study of the Scoliosis Research Society. J Bone Joint Surg (Am) lems as the interval between lengthening procedures increased. 1995; 77: 823-827. The VEPTR devices are less likely to break when compared 22. Nachemson AL, Peterson LE. Effectiveness of treatment with a brace in girls who have adolescent idiopathic scoliosis: a prospective, controlled study based on data from with growing rods. Meanwhile, spontaneous spinal fusion adja- the Brace Study of the Scoliosis Research Society. J Bone Joint Sur (Am) 1995; 77: 815- cent to the device is uncommon but infection and soft-tissue 822. scarring are common, while drifting of the rib and spinal anchor 23. Noonan KJ, Weinstein SL, Jacobson WC, et al. Use of the Milwaukee brace for progressive idiopathic scoliosis. J Bone Joint Surg (Am) 1996; 78: 557-567. points can occur. With repetitive lengthening the expansion por- 24. Goldberg CJ, Moore DP, Fogarty EE, et al. Adolescent idiopathic scoliosis: the effect tion of the device can be outgrown and requires exchanging, of brace treatment on the incidence of surgery. Spine 2001: 26: 42-47. which is a more extensive procedure compared with simple 25. Karol LA. Effectiveness of bracing in male patients with idiopathic scoliosis. Spine lengthening.54 2001; 26: 2001-2005. 26. Dickson RA, Weinstein SL. Bracing and screening: yes or no? J Bone Joint Surg (Br) 1999; 81: 193-198. 27. Dolan LA, Weinstein SL. Surgical rates after observation and bracing for adolescent idiopathic scoliosis: an evidence based review. Spine 2007; 32: S91-S100. Mr M Stenning MBBS, MPhil, FRCS (Tr & Orth) 28. Bunge EM, de Bekker-Grob EW, van Biezen FC, et al. Patients’ preferences for Mr I Nelson MBBS, MChOrth, FRCS. scoliosis brace treatment: a discrete choice experiment. Spine 2009; 35: 57-63. Department of Orthopaedic Spine Surgery 29. Coillard C, Leroux MA, Zabjek KF, et al. SpineCor- a non-rigid brace for the treat- North Bristol NHS Trust ment of idiopathic scoliosis: post-treatment results. Eur Spine J 2003; 12: 141-148. Frenchay Hospital 30. Sang Wong M, Cheng JCY, Lam TP, et al. The effect of rigid versus flexible spinal Bristol BS16 1LE orthosis on the clinical efficacy and acceptance of the patients with adolescent idio- Email: [email protected] pathic scoliosis. Spine 2008; 33: 1360-1365. 4 M. STENNING, I. NELSON

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