Study design
A prospective, longitudinal cohort study will be conducted at the outpatient clinic of the department of orthopaedic surgery of the University Medical Center Groningen (UMCG).
The collection of the data will be part of the usual follow up for patients with adolescent idiopathic scoliosis. Approval has been requested from the Medical Ethics Committee for this study, but ethical approval was waived by the Committee, since the collection of the data is part of the usual care in our outpatient clinic.
Informed consent is obtained from each patient and his or her parents before data collection.
Identification and recruitment of study participants
Patients between 8 and 17 years old, visiting the outpatient clinic of the UMCG with adolescent idiopathic scoliosis will be participating in this study. The Cobb angle should be >10 degrees, measured by an experienced observer on an AP X-ray of the total spine.
Patients should not have had previous spinal surgery; there should be no evidence of neuromuscular disease or skeletal dysplasia, and no evident abnormalities of maturation or height. Furthermore, patients with mental incapacitation are excluded since this can influence the reliability of the measurements in the way that these patients most often can not stand still during the height measurements and EMG measurements. Patients are excluded as well when they are participating in a different study simultaneously.
The assessment to include or exclude a patient will be determined by the orthopaedic surgeon. All patients who meet the inclusion criteria will be asked to participate in this study and give their informed consent.
Study protocol
The study protocol will be incorporated in the usual care of patients visiting the outpatient clinic for follow up of adolescent idiopathic scoliosis. Follow up will take place every six months. Patients will be followed until 18 years of age or until growth of the spine has stopped and skeletal maturity has been reached. Furthermore, patients will be lost to follow up when they receive surgical treatment.
A description of the (follow up) consult is presented below.
Anamnestic questions
Besides the regular anamnestic questions (general history, medication, family history, general demographics, present complaints, etc), patients are asked for:
Physical examinations
Regular physical exam of the back is done including inspection, determination of the range of motion, and the Adam's forward bending test.
Measurements are taken for total height, sitting height, lateral arm span, foot length, shoe size, and weight. Subischial leg length is calculated by distracting sitting height from total height. All length measurements are measured three times per visit, to the nearest mm, and an average will be calculated.
Measurement of total height is done by use of a stadiometer constructed according to the internationally agreed assignments and with digital reading. The patient is asked to stand upright with bare feet, having their feet parallel together, and the back of the head touching the upright steel rod against the wall. The child is encouraged to stretch out to the maximum by applying gentle pressure upward under the mastoid process, with the recorder watching to see that the heels are not off the ground. The recorder measures height by lowering the horizontal bar of the stadiometer, making contact with the top of the head. No height corrections are made for curve magnitude.
Sitting height is measured with similar height measuring equipment, while the patient sits on a table with exact known height. The patient is asked to sit straight and the legs hanging freely from the ground. Furthermore, measurement of sitting height is similar to the measurement of total height.
Lateral arm span is measured using a tape measure, from the end of the long finger of one hand, to the end of the long finger on the other hand, with arms maximally outstretched. The tape measure is confirmed to the wall, and the patient is asked to stand straight against the wall and stretch out the arms horizontally.
Foot length and shoe size are measured with a validated calliper in which length in mm and standardized shoe size can be determined. Each patient's bare left and right foot are measured individually while standing full weight bearing. The patient stands in the calliper with the back of the heel against the stationary arm, and the movable arm is brought into contact with the tip of the longest toe. The length is measured to the nearest mm, and shoe size to the nearest half-size.
Weight is measured on a validated scale to the nearest 0.1 kg.
Secondary sexual characteristics are determined by the Tanner criteria for breast development and pubic hair development. Determination of the Tanner stage is performed by a trained female observer. Furthermore, patients are asked for self evaluation of the secondary sexual characteristics according to a figure of the Tanner stages. Patients and their parents point out the figure of which they think is most representative. The reliability of self evaluation will be determined by calculating the correlation between the stages of the patient and the trained observer.
X-ray examinations
Since a clinically important increase in curve severity exists between morning and evening [31], all X-ray examinations are taken in the morning using a standardized X-ray protocol. Brace treated patients are required to remove their brace the morning of the X-ray examination.
All X-ray examinations are performed with a new ultra low dose 2D/3D digital X-ray system (Biospace Med, Paris, France).
This system allows for the simultaneous acquisition of two orthogonal planar images in a vertical scanning mode. The gantry is composed of two sets of detectors and X-ray tubes positioned orthogonally and supported by a mobile C-arm. This C-arm moves vertically using a linear scanning technique. The patient is positioned at the intersection of the two X-ray beams which scan the patient vertically, as illustrated in Figure 1. A single scan will simultaneously produce both AP and lateral images of the patient. A huge advantage of making a total body X-ray is that multiple measurements can be performed in just one single X-ray.
On the AP X-ray the scoliosis is classified and the Cobb angle is measured according to internationally agreed standards. The length of the scoliotic spine is measured from the upper end-plate of T1 to the lower end-plate of L5 (Figure 2), according to a previously described method by Cheung et al[32]. Furthermore the axial rotation and lateral deviation of each vertebra are determined.
Determination of the state of the triradiate cartilage is performed on the AP X-ray of the pelvis (open or closed), as well as determination of the Risser stage (stage 1-5).
Skeletal age of the hand and wrist is determined by a trained observer according to the method of Tanner and Whitehouse. Skeletal age of the elbow is assessed by the Sauvegrain method, using a scoring system for four anatomical landmarks of the elbow[28].
Complementary examinations
An electromyography is made of the paraspinal muscles in order to determine the ratios of muscle activity on the convex and concave side of the main scoliotic curve.
For the electromyographic measurements, 12 EMG electrodes are placed symmetrically along the superficial erector spinae muscles at three levels, 30 mm from the midline, and parallel to the spinous processes (figure 3). The electrode levels correspond to both end vertebrae of the curve (most tilted ones), and the apex vertebra (Figure 3).
The ECG is measured from two electrodes at the sternum and ictus cordis. The electrodes are connected to a multichannel recording device (Porti system, TMS International, Enschede, The Netherlands). Raw EMG signals are amplified, AD-converted, and stored at a sampling rate of 800 Hz in a computer for analysis. The EMG signals are full-wave rectified and low-pass filtered. Reliability data for these specific EMG measurements are available from Cheung et al [3].
The EMG signals are recorded in 5 postures: 1) with the patient in a relaxed upright standing posture with the arms along the body and feet together, 2) with the patient bending to the right, 3) with the patient bending to the left, 4) with the patient bending forward, 5) with the patient sitting in a relaxed position in a chair, with the arms along the body and the back against the chair.
The paraspinal activity (EMG) ratio is defined as the EMG activity of the erector spinae muscles between a convex electrode pair divided by the EMG activity between a contralateral concave electrode pair. The EMG ratios of all 3 levels are considered.
Outcome measurements
Longitudinal data will be acquired for:
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Scoliotic curve progression (in degrees Cobb angle)
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Height, and growth velocity of height
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Sitting height, and growth velocity of sitting height
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Leg length, and growth velocity of leg length
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Foot length, shoe size, and growth velocity of foot length and shoe size
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Weight, and growth velocity of weight
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Spinal length, and growth velocity of spinal length
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Tanner stage of secondary sexual characteristics
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Riser sign and status of the triradiate cartilage
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Skeletal age in hand, wrist, and elbow
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EMG ratios of the paraspinal muscles
Finally, an algorithm will be developed for predicting peak growth velocity of height and curve progression in individual patients with adolescent idiopathic scoliosis (see Figure 4).
Time frame
The first patients will be included in January 2010. An exact date for ending of this study is not provided as it will be incorporated in the usual care of AIS patients, and it is aimed to proceed for the coming years. The first evaluation of the results is expected to take place 2.5 years after the start of the study, in July 2012. In that time, 25 patients are expected to have fulfilled a two-year follow up time.
Sample size and statistical analysis
The maximum sample size of this study is not determined on beforehand, as the study is aimed to proceed for the coming years.
We aim to perform a first preliminary analysis of the longitudinal data when patients have a follow up of at least 2 years. As the expected number of new patients is 60 each year, it will take 2.5 years for 30 patients to reach a follow up of at least 2 years. Taking a loss to follow up into account due to surgical treatment, we expect to be able to analyse the complete data of at least 25 patients. The statistical power will increase with a longer follow up and more patients. The number of 25 patients was checked whether it was large enough to obtain a good prediction model according to the criteria of Knofczynski and Mundfrom [33]. With a significant large influence of 4-5 predictor variables (as is expected in this study) and a squared multiple correlation coefficient between 0.5 and 0.7 between 25 and 65 patients should be included. Therefore the first preliminary analysis will be performed using data of 25 patients.
Individual data charts are made, and results of each parameter are plotted against the growth velocity of total body height and the curve progression.
All statistical calculations are made using SPSS (SPSS Inc, Chicago USA). Pearson correlation coefficients are computed for each individual possible related parameter against the peak growth velocity and the curve progression (Figure 5). A correlation above 0.70 is believed to be clinically relevant. To be able to interpret this value in a reliable way, we will report the confidence intervals as well.
Multiple linear regression analysis of the data is used to determine predictive equations for the timing and magnitude of the peak growth velocity of height, and the scoliotic curve progression.
Missing data concerning individual parameters are not expected in this study. I.e. when a patient misses his or her follow up consult, all parameters will be missing and therefore no correlations can be calculated for that time point. It is not expected that when a patient does come to the outpatient clinic, for example the sitting height will not be measured and all the other parameters will be measured. If it does happen anyway that one individual parameter is missing, imputation techniques will be applied during data analysis.