Spinal muscular atrophy (SMA) is a rare disease that has devastating effects on the neuromuscular system. The disease generally results from homozygous absence of the SMN1 gene, affecting creation of the SMN protein needed for lower motor neuron survival.1–3 The consequences of this genetic mutation includes progressive weakness and in most children, especially those with the more common severe and intermediate subtypes (types I and II),4 results in a shortened lifespan due to progressive respiratory failure.5,6
In addition to respiratory complications, children with SMA types I and II almost universally develop spinal deformity, often at a very young age.7 Despite being difficult to treat historically, surgical management with posterior (distraction type) growing rods has emerged as safe and effective for curve correction.8,9 Treatment has been advocated as it is believed that these procedures allow increases in lung volume over time as the thorax is lengthened while preventing curve progression. Maximizing lung growth and development is especially appealing in this population due to their fragile respiratory state. However, it has previously been shown that when compared with those with idiopathic early-onset scoliosis, patients with SMA have much smaller yearly improvements in spinal height and more rib collapse after growing rods treatment.9 Thus, while assumed, the benefits of growing rod treatment on the pulmonary function in children with SMA has not been clearly demonstrated.
The objective of this study was to determine the impact of posterior growing rods on the spinal alignment and respiratory function of children with types I and II SMA at intermediate term follow-up. Our hypothesis was that growing rods would improve and maintain spinal alignment and stabilize pulmonary function.
This retrospective longitudinal analysis was completed with approval from the University of Wisconsin-Madison Health Sciences Institutional Review Board. Medical records were reviewed for children with SMA who had received dual posterior (distraction type) growing rods at our institution between 2004 and 2010 that had a minimum of 2-year follow-up. The child’s SMA subtype, age at growing rod insertion, dates of lengthenings, and pulmonary support and pulmonary function test (PFT) results were recorded. Radiographic measurements were made using digital radiographs and measurement tools available through our clinical picture archiving and communicating system (Mckesson, San Francisco, CA).
Spinal radiographs were reviewed for Cobb angle (of the major curve), pelvic obliquity, thoracic and lumbar heights, the space available for the lung (SAL), rib vertebral angle (RVA), rib vertebral angle difference (RVAD), thoracic kyphosis, and chest width and depth. These measurements were repeated on preoperative, postoperative, and most recent radiographs available. SAL is a measurement described by Campbell et al10 and is done on standard x-rays. The value is a ratio of the heights of the 2 hemithoraces. The value suggests asymmetry in the thorax and inhibition of growth of 1 hemithorax. This value allows for comparison across multiple sizes of children and is insensitive to growth, so can be used to follow the severity of impairment even as a child grows. An example of these measurements can be found in Appendix I (Supplemental Digital Content 1, http://links.lww.com/BPO/A81)23,24.
The medical record was reviewed for available PFT. When available, forced vital capacity (FVC), percent predicted FVC (%FVC), maximal inspiratory pressure, and maximal expiratory pressure were recorded before lengthening, after lengthening, and at most recent follow-up (N=6). %FVC was calculated using Zaplatel reference equations for all subjects under 8 years of age. For subjects 8 year of age and older the Zaplatel reference equation was used until 2011 when the percent predicted reference equation was changed to National Health and Nutrition Examination Survey (NHANES). All reference equations are determined based on height, age, and sex.11 FVC and FVC percent predicted is a reliable measure in children with SMA.12,13 However, due to reduced strength, not all patients (especially those with the more severe type I SMA) were capable of completing PFT. Therefore, the charts of all patients were also reviewed to determine their baseline need for respiratory support. Both the type of support, for example, noninvasive positive pressure ventilation (NIPPV) with bi-level positive airway pressure and the number of hours per day were recorded at similar time periods as PFT (ie, before surgery, after surgery, and most recent).
To analyze the radiographic variables paired t tests with Holm adjustment for 2 tests were used to determine if patient data were different at presurgery versus postsurgery and postsurgery versus most recent follow-up. Significance was set at P≤0.05. Patients were only included in a particular statistical test if values existed for both time points being compared in each particular test. Step-wise comparisons of PFT variables were compared between time points, using a paired student t test.
Sixteen children with SMA met inclusion criteria. Five of the children had SMA type I, while 11 had SMA type II. The average age of insertion was 5.8 (±1.5) years, the median number of lengthenings was 4 (range, 3 to 5), and the median time between insertion and last clinical review was 4.7 (range, 2.7 to 9.5) years. Eight of the 16 children had completed the lengthening process. Only 1 of the 8 underwent definitive fusion.
Radiographic review demonstrated significant (P<0.05) improvements in the following: major curve magnitude as measured by Cobb angle, pelvic obliquity, thoracic and lumbar heights, the SAL, RVAD, and thoracic kyphosis following growing rod implantation. Thoracic and lumbar height continued to increase significantly (P<0.05) over the lengthening process. although chest width and depth increased, only chest width changes reached statistical significance. Finally rib collapse, as measured by the RVA, did not change significantly throughout the process. These findings are summarized in Table 1, and radiographs of a patient during the lengthening process are demonstrated in Figure 1.
None of the 16 patients required more than NIPPV support at baseline and only 1 patient had an increase of their respiratory support. This child required the addition of NIPPV use at night. Except for this one patient, none of the 16 patients experienced significant changes in their positive pressure respiratory support needs. All patients required support only at night and naps. One child with SMA type I recently died, cause of death was determined to not be respiratory in nature.
Serial PFTs were available for 6 children with SMA type II. PFTs demonstrated significant improvements in absolute FVC. On average, children improved 0.41 L from initial testing to final follow-up (SD±0.25 L; n=6, P<0.05). %FVC showed an average decline over time. Patients (n=5) began with an average of 48% of expected FVC and declined to 35% at latest follow-up (P<0.05). Inspiratory and expiratory respiratory muscle force pressure as a group appeared to stabilize over the testing, with some patients showing improvement and others showing decline. Average maximum inspiratory pressure increased from a preoperative value of 33 to 43 cm H2O postoperatively and 49 cm H2O at latest follow-up (n=4), but none of these changes were statistically significant (P=0.22, 0.24, respectively). Maximum expiratory pressures stayed nearly constant with average values of 29, 30, and 28 cm H2O at preoperative, postoperative, and latest evaluations, respectively. Figure 2 demonstrates these PFT findings.
The purpose of this study was to determine the effects of posterior growing rods on the spinal alignment and pulmonary function of children with SMA. Because of the relatively rare occurrence of this disease, this is the first single center study, using a uniform spinal treatment, to evaluate the pulmonary outcomes that this surgery has on a population of children with SMA. Our results indicate that spinal deformity is improved and maintained over the long term. Further, FVC was found to increase after surgery. However, %FVC has the opposite trend, actually reducing over time.
Traditionally, scoliosis in SMA had been treated with bracing and/or early fusion. However, bracing was found minimally effective and lead to problems with respiration.14,15 Similarly early fusion did not always stop curve progression16 and is thought to reduce maximal lung volumes.14,17,18 Because of these consequences, other treatments approaches have been sought in this population. Surgical placement of growing rods as treatment gained favor after Chandran et al8 showed much improved spinal curvature with very few complications (none surgical), and increased FVC at 9 months of follow-up (0.53 to 0.67 L). Another group, demonstrated improvement even when curves began much larger (89 to 55 deg. at 55 mo of follow-up).9 Despite these gains, this study showed that rib collapse continued in the children with SMA. However, neither of these studies determined whether pulmonary benefits would persist over time following growing rod insertion. In our study, the average most acute RVA did not change, over the study period, the average chest width and average trunk heights (sum of thoracic and lumbar heights) increased during the lengthening process. All of these radiographic findings likely contributed to our generally favorable pulmonary results.
Our PFT results mirror other studies evaluating the surgical treatment of early-onset scoliosis associated with different devices or a variety of diagnosis. Dede et al19 reported that the use of VEPTR in children with early-onset scoliosis due to a variety of conditions led to large improvements in FVC [a 45% improvement (0.31 L) at 72 mo]. However, similar to our results, these children had reduced %FVC (77% to 58%).19 Other work, however, has shown increases in %FVC. A study of 6 children with neuromuscular disease with magnetic growing rods showed an improvement of 14% %FVC at an average of 30 months of follow-up.20 Comparing our results with recently reported PFTs for children with type II SMA, it does appear we are improving FVCs over the natural history and perhaps slowing the rate of %FVC decline.21
Pulmonary function is a major issue in children with SMA. A majority of children die to pulmonary compromise, due to restrictive lung disease with progression to respiratory failure. Therefore, sources of gain or stabilization in pulmonary function are often sought. Given that scoliosis is known to limit SALs and hinder lung development,22 treatment of scoliosis at an early age is hypothesized to improve pulmonary function. From our results, we are encouraged by the increases in FVC seen over time and the stabilization of the inspiratory and expiratory respiratory muscle pressures. The reduced %FVC could be in part due to continued change in rib shape or further reduction in chest wall and lung growth of the child relative to their length compared with normal (altering the effects of normalization over time). Time between lengthenings being less than ideal could also contribute to reduced %FVC, though risks of surgery must be weighed before increasing frequency.
Although we feel this study presents valuable new information, we should acknowledge the following limitations. First the study lacks a control group. It is unclear whether children with SMA not receiving growing rods would show similar changes in their lung volumes over time. Another limitation is the small sample size, especially of children actually receiving full PFT. Furthermore, our study included patients who were too young or too weak to complete standard PFT. Inclusion of this group is important to characterize the change in pulmonary function in this severely affected group. Despite the disease severity of this group (many SMA type 1), we surprisingly found that only 1 patient had an increase in respiratory support during this period and most needed NIPPV only during sleep. Another potential shortcoming of this study was the inability of to capture or quantify adverse respiratory events in the perioperative period. The authors did not identify these events in the study design and while doing so may have strengthened this manuscript such data would have required a prospective design to capture. Also using 3-dimensional imaging may have provided more accurate measurements of changes in thoracic volume, but this imaging is not routinely obtained serially. Because of the rare nature of the disease, we feel that the new information provided on these patients can give insight not provided to date.
In conclusion, in children with SMA, posterior growing rods can stabilize spinal deformity over time. Further, after implantation, vital capacity improves, but the %FVC tends to decrease. The need for pulmonary supportive therapy remains relatively stable. From these findings, we conclude that growing rods may help to stabilize pulmonary function and slow decline, although this cannot be stated with certainty due to a lack of a comparison group. Because of the fragile pulmonary status of children with SMA, growing rods are a good option for patients to help achieve spinal and pulmonary stabilization.
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spinal muscular atrophy; SMA; growing rods; pulmonary function testing; PFT; respiratory; scoliosis; spinal deformity
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