|Year : 2022 | Volume
| Issue : 3 | Page : 117-122
Prognostic factors to predict the progression of adolescent idiopathic scoliosis: A narrative review
Amrit Gantaguru1, Nandan Marathe2, Alhad Mulkalwar3, Abhinandan Reddy Mallepally2
1 Department of Orthopaedics, S.C.B. Medical College and Hospital, Cuttack, Odisha, India
2 Department of Spine Services, Indian Spinal Injuries Centre, New Delhi, India
3 Intern, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Parel, Mumbai, Maharashtra, India
|Date of Submission||16-Apr-2022|
|Date of Decision||01-May-2022|
|Date of Acceptance||29-May-2022|
|Date of Web Publication||1-Sep-2022|
Intern, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Acharya Donde Marg, Parel, Mumbai 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Scoliosis has always presented a challenge to the clinicians both at the stage of decision-making and at the stage of correcting the same. Predicting curve progression is important as it helps in selecting the patients who may benefit from an earlier intervention. Patients can be treated either by brace application or by operative intervention depending on the magnitude of curve and potential of curve progression. In this review, we have summarized the past and present parameters used to predict scoliosis progression with a brief introduction about the future trend in this respect. We identified and reviewed a total of 46 relevant papers written in English language utilizing PubMed, Google Scholar, and Scopus search engines. Many clinicians had come up with various radiological methods such as Risser grading, Tanner–Whitehouse staging (TW2-RUS and TW3) methods, Greulich–Pyle method, Sauvegrain method using only olecranon process radiographs and various clinical methods such as age of menarche and Tanner staging for sexual maturity. Apart from these, recently, various genetic factors such as single-nucleotide polymorphism of various genes, platelet calmodulin, peripheral blood mononuclear cell, impairment in melatonin signaling, DNA-based test called “ScoliScore” and hormones such as serum ghrelin and leptin have been investigated. Changes in brainstem vestibular function and alteration in electrical activities of paraspinal muscles are also studied to predict the curve progression. The two most important dilemmas faced by clinicians while approaching patients with scoliosis are the identification of patients requiring intervention and the right time to intervene in the selected patients. The goal of scoliosis treatment is to halt the progression. Predicting the growth spurt in an individual patient will guide the appropriate timing of intervention which can prevent complications associated with adolescent idiopathic scoliosis so that they can lead a better quality of life.
Keywords: Biomarkers, curve progression, genetics, Risser, RUS, Sauvegrain method, scoliosis, Tanner–Whitehouse
|How to cite this article:|
Gantaguru A, Marathe N, Mulkalwar A, Mallepally AR. Prognostic factors to predict the progression of adolescent idiopathic scoliosis: A narrative review. J Orthop Dis Traumatol 2022;5:117-22
|How to cite this URL:|
Gantaguru A, Marathe N, Mulkalwar A, Mallepally AR. Prognostic factors to predict the progression of adolescent idiopathic scoliosis: A narrative review. J Orthop Dis Traumatol [serial online] 2022 [cited 2023 Jan 28];5:117-22. Available from: https://jodt.org/text.asp?2022/5/3/117/355247
| Core Tip|| |
The decision about patient selection and appropriate timing of intervention in scoliosis depends on ability of the treating clinicians to predict the potential for curve progression. This carries more importance for low magnitude curves as the curves with greater Cobb value have higher chance of progression and require intervention at the time of presentation. In this review article, we have described the various radiological parameters and clinical parameters that have been developed over years to predict curve progression. We have also presented a brief review about the genetic markers and biomarkers under evaluation which may prove to be helpful in the future.
| Introduction|| |
Scoliosis is defined by a lateral spinal curvature (≥10°) including rotational component, without any neuromuscular cause or genetic origin, usually diagnosed between the ages of 10 and 16 years, prior to skeletal maturity. Of the various subtypes of scoliosis, adolescent idiopathic scoliosis (AIS) is the most prevalent form, accounting for 80% of pediatric scoliosis. It is a very common disease with a prevalence of 2%–4%. Scoliosis has been an unanswered question for many centuries. The first successful example of spine deformity correction can be found in the ancient Hindu scripture Shrimad Bhagwat Mahapuranam at around 3500 B. C. God Shri Krishna corrected hunchback deformity of a female devotee by traction. He stabilized her back by applying force and gave traction by pulling her chin. Hippocrates who defined scoliosis treated patients by strapping onto a traction developed by him which was called Hippocrates board or ladder. Over the last few centuries, scoliosis management underwent numerous changes by the application of different modalities like bracing by Pare (1510), posterior fusion by Hibbs in 1900s, and more importantly in the 20th century due to instrumentation developed by Harrington. The Harrington rod system gradually evolved into the current era of posterior pedicle screw fixation system, which enables better control of all three columns of the spine for the achievement of maximum correction and maintenance of the same. The potential of a curve to progress is one of the important deciding factors for intervention. Numerous clinical criteria, radiological features, genetic markers, and other chemical biomarkers have been described to predict which children, diagnosed with mild disease, will undergo subsequent curve progression. Older scoliosis literatures used definitions of curve progression such as 5° or 6°. However, current trend is to use physiological endpoints such as slowing of the rapid infantile growth, the start and end of the growth spurt, and progression during adulthood. Ascertaining the peak height velocity (PHV) in patients with AIS is essential to provide timely treatment to halt deformity progression. To provide maximal benefits of any intervention, predicting when curve progresses at its greatest extent is vital. Uncertainty regarding curve progression and outcome can create anxiety in families and patients with scoliosis as well as unnecessary psychosocial stress associated with conservative treatment. The failure to accurately predict the risk of progression can also lead to nonoptimal treatment, either by precluding timely, appropriate, and efficient management, or by generating unnecessary medical visits and radiographs. This review article aims to summarize these criteria and provide an update on current trends and research while throwing light on future perspective on card.
| Natural History|| |
To the authors' knowledge, two series of AIS patients without treatment with long-term follow-up exists: by Stockholm and Gothenburg. In the Stockholm series, 90% of 113 patients were evaluated from 1913 to 1918. They were followed a minimum of 45 years, or until their death. The Gothenburg series included 130 patients with scoliosis of any cause enrolled from 1927 to 1936 at the age of 0–30 years. There were no deaths in patients with adolescent (aged 10–16 years) scoliosis of unknown etiology. Thus, it is safe to say that AIS does not result in an increased mortality rate. However, it may have detrimental effects on cardiopulmonary function, quality of life, appearance/cosmesis, back pain, pregnancy, etc. In a study of 800 patients with idiopathic scoliosis attending a chest clinic over 25 years, 11 had died of cardiorespiratory failure due to scoliosis. Thus, predicting the natural history and managing curves with a potential to progress is of vital importance. A clear understanding of the natural history of scoliosis would be an important contribution to the development of the best overview for patients and consequently the best therapeutic strategies. To identify the appropriate treatment, avoiding overtreatment or undertreatment, it is essential to know the rates of progression of scoliosis.
| Pathogenesis of Curve Progression|| |
It is believed that the growth cartilage on the concave side becomes overloaded and its growth gets inhibited. Recent studies suggest that initial scoliotic deformity progresses during growth spurt through the intervertebral discs with bone deformity occurring later implying an initial soft tissue imbalance with the Hueter–Volkmann principle acting later in maturity. It is thought that adult deformities progress primarily through disc degeneration. Many known radiographic parameters were developed to aid in predicting PHV of the long bones. A correlation between curve acceleration with timing of PHV was identified by these studies but is highly variable and has limited utility for clinical decision-making. Thus, even with accurate prediction of growth rates, there are still difficulties in predicting when and how each patient may deteriorate with regards to different growth phases. The ability to predict which patients with AIS undergo curve progression and how curve progression can be predicted by growth is still limited. Accurate prediction of curve progression risk at its peak with reference to patient's growth potential is essential to maximize the benefits of any intervention. This can be determined by assessing how growth and curve progression rates match in patients with AIS. Decision-making is based on the clinician's experience, the patient's growth rate, and Cobb angle on presentation. It therefore is necessary to correlate the curve progression of AIS with natural growth to refine our understanding of the period of actual curve progression risk so that interventions can be provided timely and only for patients who really need it.
| Clinical Predictors|| |
The logical approach to a patient with scoliotic deformity is firstly to rule out primary nonidiopathic etiology leading to scoliosis. The second is to determine if the idiopathic curve will progress and create potential long-term complications. Remaining growth potential of spinal column is the key predictor for the progression of idiopathic scoliosis. Determining this remaining growth potential can help to take decision for use of orthosis to halt further progression of curve and avoiding spinal fusion at skeletal maturity.
Lonstein and Carlson pointed out that three strong progression factors for idiopathic scoliosis were the curve magnitude, patient's chronologic age, and the Risser sign. The main progression of idiopathic scoliosis occurs at the time of most rapid adolescent skeletal growth, which is a critical period in the evolution of spinal deformity and for its outcome. It has also been confirmed that PHV is a reliable clinical marker for predicting leftover growth potential and progression of scoliosis. This time of peak growth velocity (PGV) occurs around 11–13 years of skeletal age in girls and 13–15 years in boys, and it is characterized by a gradual increase in the spinal growth rate. Patients presenting with juvenile idiopathic scoliosis will go through this entire period of pubertal growth and, therefore, need systematic follow-up on their growth curve. The determination of secondary sexual characteristics as well as skeletal age are helpful in the evaluation of skeletal maturity in addition to 6 monthly height measurements. Perdriolle and Vidal stated that the main increase in juvenile scoliosis occurs between the age of 6 years and the Tanner pubic stage 2, followed by a lesser progression during the adolescent growth spurt.
The best method for detecting the beginning of the pubertal growth spurt is to measure the child's standing and sitting height regularly at 6 monthly intervals and match these data with skeletal ages from the left hand and wrist and the left elbow. The mean increase in sitting height is about 3.5 cm per year in girls and 4 cm per year in boys. Apart from PGV, skeletal age data and the assessment of secondary sexual characteristics are helpful as additional parameters that allow precise mapping of the patient on the pubertal growth diagram.
Several indicators for predicting PGV include combination of different factors such as the chronological age, skeletal age, Risser sign, and age of menarche. Multiple studies have reported on the correlation between age and curve progression. Literature, including prospective and retrospective studies, report patients <13 years of age at diagnosis, had a higher risk of curve progression. Another factor consistently reported is the status of menarche. Premenarche patients are at a higher risk and this forms a part of clinical assessment of all female scoliosis patients. Menarche is a readily identifiable maturity indicator. However, it always occurs after PHV. Furthermore, it is too variable for accurate assessments. The pubertal or Tanner stages are highly correlated with the growth spurt and PHV. Girls reach PHV at around stages 2 and 3-for breast and stages 2–3-for pubic hair. Boys reach PHV at around stages 3 and 5 for penile and testicular growth.
However, these methods are not accurate enough in predicting individual child's growth. Furthermore, growth indicators like skeletal age of hand and wrist/Tanner staging of sexual characteristics need highly trained judgment for an accurate assessment. To improve accuracy, Busscher et al. developed a mathematical model, wherein partial individual growth velocity curve was linked to the generic growth velocity curve. This model reported higher accuracy in predicting the individual age and magnitude of the PGV.
| Radiological Predictors|| |
Despite contemporary methods, evaluation and follow-up of AIS still consists of repeated visits with radiological imaging. Whole-spine X ray on a 14 × 36 inches cassette is ideal to evaluate scoliosis. The scoliosis radiograph must span cervical spine to pelvis. Furthermore, it is essential to include cranium down to both femoral heads for sagittal balance assessment (C2 and C7 plumb lines as well as several pelvic parameters) and for planning of correction and after surgery in AIS. The most common measurement of spinal curvature used is the Cobb angle using maximally tilted endplates.
In AIS, the primary clinical utility of the Cobb angle is to determine the risk of curve progression. Curves with high Cobb angle values are less prevalent. Approximately 0.2% curves are >30°, and approximately 0.1% are >40°. The ratio of female to male for curve magnitude >30° is 10:1. Higher initial Cobb angle at presentation is associated with more curve progression. Furthermore, the curve pattern influences the prognosis. Thoracic and thoracic predominant double major curves (Lenke type 1 and 3 curves) are associated with earlier and more rapid curve progression. Deformity with larger magnitude, Cobb angle alone may not imply progression. Degree of apical vertebral rotation, sagittal balance using a C7 plumb line in relationship to pelvis, or ilio-costal distance clinically suggest a progressive deformity. In a study of 727 patients with AIS with curve magnitude between 5° and 29°, magnitude of the curve, skeletal maturity, and patient's menarche status were shown to be major predictors of deformity progression.
Skeletal maturity is usually determined by degree iliac crest apophysis ossification. In Risser stage 0, the apophysis is not present. Risser 1 usually occurs after the growth peak. Critical reviews of Risser's sign have found that it is no better than chronological age. Deformity in immature skeleton Risser “0”were found to progress in 65% with curves between 20° and 30° and in nearly all patients with a curves > 30°. While Risser staging is convenient, as the pelvis can typically be included on screening radiographs for scoliosis, it also has several drawbacks. The iliac apophysis is more difficult to see on posteroanterior radiographs, which are currently preferred to decrease the amount of radiation to breast tissue. Furthermore, the first visible ossification of the iliac apophysis (Risser stage 1) typically occurs well after PHV, which is the most important period of potential scoliosis curve progression. In addition, the iliac apophysis may not ossify in a uniform lateral-to-medial pattern, and in some cases ossification may even begin before closure of the triradiate cartilages, all of which make accurate Risser staging difficult.
Two other important methods developed for assessment of skeletal maturity include Greulich–Pyle (GP) method and Tanner–Whitehouse (2) methods (TW2) both of which use left hand and wrist radiographs. Left hand is preferred as most individuals are right-handed so there is less chance of injury to left hand. Furthermore, it was decided in the conferences of physical anthropologists in the early 1900s to take all measurements from the left side of body. The GP method which is an atlas method was developed using the radiographs of upper middle class Caucasian children in Cleveland, Ohio, United States between 1931 and 1942. Current generation children attain secondary sexual characteristics earlier than their contemporaries few decades ago when the atlas was developed. Therefore, GP method might not be accurate in predicting the maturity of present generation children hence it is less useful.
The TW2 methods comprise three different methods. The RUS or radius-ulna-short bones method which evaluates 13 bones including radius, ulna, and short bones of first, third and fifth fingers. The second is the carpal method that evaluates 7 carpals and lastly 20 bones method to evaluate the 13 long and short bones and 7 carpals. The TW2 method is a scoring method where initial staging of bones is done based on maturity level from A to H or I. Total score is calculated by replacing each stage by a score which is then transformed into bone age. The radiographs for TW2 method were collected between 1950s and 1960s which include children from average socioeconomic group from United Kingdom.
The Tanner–Whitehouse 3 method was developed in 2001 to update the relationship between total bone maturity score and bone age. The epiphyses of the hand form and fuse in an ordered fashion. The phases of importance are uncovered, covered, capped, fusing, and fused which forms the basis of the Tanner–Whitehouse staging. Covered epiphysesare as wide as the metaphyses (radial to the ulnar side). Capped epiphyses curl over the edge of the metaphyses (proximal to distal). In the fusion stage, epiphyses join the metaphyses, (distal to proximal). Curve acceleration phase corresponds to epiphyseal capping which corresponds to Risser 4 with < 2 cm of growth remaining. There is approximately a year of slow growth remaining.
Charles, DiMeglio, and others from their group in Montpellier used Sauvegrain method and a modification using just the olecranon. Preliminary work indicates that unlike the Risser sign, hand and elbow skeletal maturity provides similar prognostic value for both boys and girls. Furthermore, a rib-vertebral angle of <65° at the apical level of the convex side, after a few months of brace treatment, is associated with further curve progression in patients with initial Cobb angle of 40°–56°. There is also a significant association between markers of osteopenia (DEXA/bone stiffness index of calcaneus) and progression of spine deformity in AIS. However, this needs further evaluation. The angle of the plane of maximal curvature is an important three-dimensional parameter. Villemure et al. found a tendency for the angle to increase with increasing Cobb angle in the frontal plane, but this is the first study to demonstrate that this parameter is a risk factor for AIS progression. It is associated with rotation of the curve and may be more sensitive for detecting AIS progression than the traditional Cobb angle.
| Future Directions|| |
Apart from the conventional clinical and radiographic parameters, the current research has looked at a few novel prognostic factors in AIS. A significant association was seen between brain stem vestibular dysfunction and spine deformity progression (increase of Cobb angle >4°), in a case series of 28 girls with AIS. Genetic analysis including single-nucleotide polymorphism of various genes, changes in Melatonin signaling, Gi and Gs protein, functional status in peripheral blood mononuclear cell, platelet calmodulin have been studied in AIS; however, their practical application is limited by the low level of evidence, small sample sizes, as well as cost considerations., A DNA based prognostic test named “ScoliScore” has been developed which provided important information in risk prediction, but the test applies only to white AIS patients.,
Most AIS patients usually present with deformity of certain magnitude on first visit and only few with severe or progressive curve require management. Literature shows that AIS is a polygenic disease. In the clinical practice, however, the value of AIS susceptibility loci and genes is limited. Genomic studies for the curve progression, however, is difficult. Epigenetic analysis may complement genetic analysis. Mao et al. chose cartilage oligomeric matrix protein (COMP) encoding COMP as a target gene for AIS curve progression and investigated methylation status in its promoter region; high COMP promoter methylation was found to be correlated with AIS curve severity.
Research has also looked at biomarkers in AIS for assessing progression. Scientists have found marked increase in serum ghrelin levels and decrease in serum leptin levels in females with AIS.,, The correlations between the two hormones and growth parameters were documented. The authors concluded that high ghrelin level may serve as a new quantitative indicator for predicting curve progression and thus helps in precise selection of appropriate treatment in AIS girls.
Asymmetry of the paraspinal muscles electrical activity by electromyography, has been associated with curve progression. All these novel parameters need to be validated in multicentric studies with large sample sizes before they become a part of mainstream use.
The two most important question that boggle clinicians' minds while approaching patients with scoliosis are which patients require intervention and when to intervene in the selected patients. We have made ample number of studies and research to achieve giant strides in treatment strategies and reduction techniques in AIS, but the present review revealed a paucity of level-1 evidence focused on development of an ideal evaluation tool or a set of diagnostic criteria, which would allow selection of patients, with a high risk of progression to severe spine deformity, for “preventive” surgical intervention at an earlier stage. The integration of traditional radiographic parameters along with the recently discovered genetic and biochemical markers responsible for development and progression of scoliosis will enable the surgeon to better predict the progression potential of curve which will lead to better patient selection for timely intervention.
| Conclusion|| |
The goal of scoliosis treatment is to halt the progression. It is essential to identify children with greater risk of curve progression from those who do not. The failure to accurately predict the risk of progression can also lead to nonoptimal treatment. Although the ability to predict which patients with AIS undergo curve progression and how curve progression can be predicted by growth is still limited, this review article highlights the need for optimal individualized treatment strategy, especially in skeletally immature patients, for better treatment outcomes.
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Conflicts of interest
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