Influence of Paraspinal Growth-Friendly Spinal Implants in Children with Spinal Muscular Atrophy on Parasol Deformity, Rib-Vertebral Angles, Thoracic, and Lung Volumes

Spinal muscular atrophy (SMA) is a rare, but severe, neuromuscular disorder with a loss of alpha motor neurons leading to progressive muscle weakness and atrophy. This is primarily caused by a deficiency of the survival motor neuron (SMN) protein due to mutation or deletion of the SMN1 gene [1, 2]. The severity of the disease ranges from very severe (SMA type I) to mild cases (SMA type IV) [2, 3]. The number of genomic copies of SMN2 is inversely associated with disease severity [4].

Children with severe SMA often develop progressive spinal deformity in combination with collapsing ribs, the so-called collapsing parasol deformity, and a pulmonary function decline [5, 6]. To control spinal deformity and supposedly support thoracic development, lung growth, and respiratory function, growth-friendly spinal implants (GFSI) have been used with a rib-to-pelvis fixation [7]. The rationale behind this technique for the treatment of collapsing parasol deformity is possible horizontalization of the ribs due to implant-induced pressure, while obtaining these effects due to repetitive surgical distractions or outpatient lengthening procedures using an external remote controller over time [7‒10]. The therapeutic success of GFSI is usually measured by the reduction of the scoliosis and/or kyphosis angle on standardized radiographs of the whole spine [11], whereas evaluation of the torsion of the spine, 3D analysis and thoracic volume has gained importance just recently [12‒14]. Another radiographically measurable deformity parameter, the rib-vertebral angle (RVA) was established by Mehta [15] in 1972. The difference of the RVA can be used to predict the progression in infantile idiopathic scoliosis [16] and has been proven to have a correlation to the scoliosis angle measurement [17]. Livingston et al. [6] and Johnston et al. [5] used different methods to evaluate parasol deformity in SMA children.

In the present study, the effects of paraspinal GFSI with rib-to-pelvis fixation in SMA children with neuromuscular spinal deformity were analyzed to predict influences on the collapsing parasol deformity via measurements of the parasol score, the RVA, thoracic, and lung volumes. Because of progressive pulmonary function decline in SMA, a larger thoracic cage may be beneficial to the overall lung function in these patients.

After Ethics Committee approval, a prospective, non-randomized cohort study was performed on 37 pediatric subjects with SMA and spinal deformity. Of these, 19 children were treated with bilateral GFSI (MAGEC^®, NuVasive, USA, or VEPTR^®, DePuy Synthes, USA) (Fig. 1) inserted parallel to the spine using a rib cradle fixation with an outrigger and pelvic hook fixation [7], whereas 18 SMA children had no prior spinal treatment (Table 1). The indication for GFSI treatment was a progressive spinal deformity in SMA, which could not be controlled by conservative treatment methods. Rib fixation was always performed in the area of rib three to seven.

The group with GFSI-treatment was evaluated prior to GFSI treatment (T0), directly after implantation-surgery (T1), after an average follow-up of 4.6 years (range 2.4–8.8 years) with GFSI treatment (T2), and upon removal of GFSI before definite spinal fusion (T3) (Fig. 2a). GFSI are removed some weeks before definite spinal fusion to minimize implant-transmitted infection from GFSI. In the group without GFSI pretreatment, definite spinal fusion was planned and the late presentation without pretreatment with GFSI was either because of late deformity, fear of surgical treatment, repeated respiratory infection, cachexia or due to a refugee status.

Clinical data relative to gender, age, body mass index (BMI), body height, and weight were collected (Table 1). Radiographs of the children were obtained in anterior-posterior and lateral standardized sitting position at all time points. On radiographs, the scoliosis angle, kyphosis, and Mehta RVA [15] were measured using Centricity Enterprise Web version 3.0 (GE Healthcare Medical Systems, USA). Using the original Mehta RVA measurement [15], a “perpendicular (line) is drawn to the middle of either the upper or lower border of a selected thoracic vertebra.” This is the datum line for that vertebra. Another line is drawn from the mid-point of the head of the rib to the mid-point of the neck of the rib, just medial to the region where the neck widens into the shaft of the rib. This rib line is extended medially to intersect the vertebral line to make the RVA” (Fig. 2b). The RVA on the convex and the concave side of the curve were measured at the level of all twelve ribs, even though some were twisted due to spinal torsion.

Parasol deformity was determined clinically by grading each hemithorax as “normal” or “parasol” at all examined time points. The parasol score was determined according to Livingston et al. [6].

Computed tomography (CT) images were taken directly before definite spinal fusion for planning of the surgery. CT images were subjected to three-dimensional reconstruction and all reconstructions with full representation of thoraces and lungs were used for measurements of thoracic and lung volumes using the software program Horos (The Horos Project, Horos version 3.3.6) (Fig. 2c, d). The apex of the lungs and the upper thoracic aperture formed the upper limit of the reconstruction, whereas it was limited by the ribs and the intercostal muscles laterally and by the diaphragm caudally. The ventral boundary was formed by the sternum and the dorsal boundary by the twelve thoracic vertebrae. The thoracic boundaries were manually drawn into the CT image, and subsequently, all regions of interest were combined and assembled into a reconstructed three-dimensional model. The measurements of the lung volumes were done using the same method with individual measures of the left and right lung, respectively.

Statistical analysis of all data was performed using Graph Pad Prism version 6 (GraphPad Software Inc., USA). Displayed in the figures are the mean and standard deviation as error bars. Some RVA could not be measured, for example, due to extreme torsion; therefore, the exact n-numbers analyzed are depicted in the corresponding bars of each graph. An unpaired t test was performed to compare RVA at each individual rib, differences in RVA (RVAD), thoracic volume, and lung volume between patients with and without GFSI. A paired t test was performed to compare the concave and convex side of each individual rib pair. Statistical significance was defined with levels as p < 0.05 (*), p < 0.01 (**), and p < 0.001 (***).

Data of 19 scoliotic children with GFSI treatment (9 female, 10 male) and 18 scoliotic children without GFSI treatment (10 female, 8 male) were analyzed (Table 1). At the time of GFSI implantation, children were on average 8.4 years old and were consecutively followed from the beginning of treatment until spinal fusion at an average age of 13.3 years. Non-treated children were 13.2 years old at spinal fusion. Comparing age, body height, weight, and BMI at the time of spinal fusion, no significant differences were found between both groups. The average scoliotic angle was 54.9° (range 17–90°) prior to GFSI treatment, 45.8° (range 12–81°) at the end of GFSI treatment, and 66.9° (range 31–91°) after implant removal. The kyphosis angle was 42.5° (range 4–85°), 46.1° (range 3–78°), and 48.0° (range 12–93°), respectively. In the untreated group, scoliosis was an average of 88.8° (range 40–147°) and kyphosis 51.0° (range 2–114°). Thus, the scoliosis angle directly before spinal fusion was different between GFSI treated and untreated adolescents (p = 0.0166).

In all SMA patients and at all times, there was a difference in the RVA between the convex and concave side with lower values of the convex side (Fig. 3). While at an average age of 8.3 years, the RVA difference between the convex and concave side was significant only in the lower thoracic region (Fig. 3a), a significant difference also became apparent in the upper thoracic region over time (Fig. 3b–d). At T0, the largest average difference between the concave and convex side was observed within rib pair 11, with the RVA on the convex side being on average 37° smaller (range 72° smaller – 21° larger) than on the concave side. At T1, the largest average difference was observed within rib pair 11 as well, with the RVA on the convex side being on average 28° smaller (range 72° smaller – 17° larger) than on the concave side. At T2, the largest average difference was observed within rib pair 8, with the RVA on the convex side being on average 34° smaller (range 93° smaller – 34° larger) than on the concave side. At T3, the largest average difference was observed within rib pair 10, with the RVA on the convex side being on average 39° smaller (range 80° smaller – 60° larger) than on the concave side.

Significant differences of the RVA of the convex and concave side were also found in the SMA group without prior treatment (Fig. 3e). Here, the largest average difference was observed within rib pair 6, with the RVA on the convex side being on average 38° smaller (range 100° smaller – 7° larger) than on the concave side.

To analyze the effect of GFSI on the RVA, the SMA treatment group was analyzed for an average of 4.6 (range 2.4–8.8) years. The RVA of all ribs was measured, but for a better overview we chose to display ribs 3 to 8 equaling the implant fixation points. Because of the fixation of rib implants, it was hypothesized that these were the ribs with the possibly most severe effect on rib horizontalization (Fig. 4). There was no difference in the RVA before (T0) and after (T1) GFSI implantation, neither on the concave (Fig. 4a) nor on the convex (Fig. 4a’) side. Comparison of the RVA before GFSI implantation (T0) and after an average of 4.6 (range 2.4–8.8) years (T2) revealed significantly higher RVA on the concave (Fig. 4b) but not the convex (Fig. 4b’) side. Thus, carrying GFSI over the course of several years significantly increased RVA in the area of implant-fixation on the concave but not the convex side. Comparing RVA directly before (T2) and after (T3) GFSI removal, there were unchanged values of the concave side and significantly reduced values for rib 4–6 on the convex side of the curve (Fig. 4c, c’). RVA of rib 4 was on average reduced by 7° (range reduction by 46° – increase by 7°), RVA of rib 5 was on average reduced by 20° (range reduction by 58° – increase by 7°), RVA of rib 6 was on average reduced by 15° (range reduction by 48° – increase by 25°).

To analyze the influence of GFSI on the collapsing parasol deformity, age-matched SMA adolescents with (n = 19) and without (n = 18) prior GFSI treatment were analyzed before spinal fusion (Fig. 2a; T3). Average kyphotic values did not differ significantly between these groups at that time point, average scoliotic values were significantly larger in patients without prior GFSI-treatment (Table 1). Comparing both groups, there was no significant difference of RVA both on the concave (Fig. 5a) and on the convex side (Fig. 5b).

To evaluate the influence of GFSI treatment on thoracic and lung volume, available CTs with full thorax images were analyzed of 9 patients with and 16 patients without GFSI treatment. In these subgroups, no significant differences were observed when comparing age, weight, height, BMI, and kyphosis. Scoliosis was significantly larger in patients without prior GFSI-treatment. There were no significant differences in the thoracic (Fig. 5c) and total lung volumes (Fig. 5d). If at all, there was a very slight trend toward reduced thoracic and lung volumes in patients with GFSI treatment. Volumes of the left lung were significantly smaller than volumes of the right lung, which is explained by the anatomy.

Collapsed hemithoraces did not change due to implantation of GFSI (Fig. 6). However, there was an increase of parasol deformity over time (between T1 and T2). Analyzing the parasol score, again, there was no difference between T0 and T1 and between both T3 groups, but an increase of parasol deformity over time (between T1 and T2) despite GFSI treatment (Fig. 6).

Most children with SMA type I or II develop spinal deformity in early childhood, which may require early surgical intervention [18]. In the past years, implantation of GFSI with bilateral paraspinal rib-to-pelvis fixation was postulated [7] and deformity control in SMA children was shown both in short and long-term follow-up using this surgical technique [19, 20]. Additional to spinal deformity, thoracic deformity in SMA children is a common sequela. Weak intercostal muscles are unable to oppose the relatively stronger diaphragm resulting in a collapse of the rib cage, a constricted thorax, and hypoplastic lungs [6]. This condition is known as the thoracic insufficiency syndrome [21]. It was assumed that SMA children with progressive thoracic collapsing parasol deformity and declining lung function [5] may benefit from a paraspinal rib-to-pelvis implant fixation with lateral outriggers due to horizontalization of the ribs, e.g., elevation of the RVAs, caused by implant pressure on the upper rib portion. In general, RVAD strongly correlates with scoliosis angles and RVAD is recommended to guide treatment decisions in idiopathic scoliosis in infantile and juvenile types [15‒17, 22, 23]. In this paper, RVA in SMA children before, during, and after GFSI treatment was assessed, and data from the last analyzed time point (after GFSI-treatment and before definite spinal fusion) were compared to age- and disease-matched controls without prior GFSI-treatment.

In all SMA children with spinal deformity, an RVA asymmetry between the convex and the convex side was found with smaller values on the convex side. This is consistent with studies on idiopathic scoliosis, where concave RVA were larger than convex values [22, 23]. For the idiopathic scoliosis patient population, RVA linearly increased with larger scoliotic angles [23]. The latter finding could not be reproduced in SMA children with spinal deformity indicating that in the SMA population RVA changes, known as the collapsing parasol deformity of the thorax, are rather related to the disease and muscle weakness itself than to scoliotic deformity. Our findings support the data of Livingston et al. [6] for hypotonic neuromuscular patients. Livingston et al. [6] found no correlation between the parasol deformity and the degree of scoliosis in their patient population.

In our study, bilateral GFSI treatment with significantly positive effects on spinal deformity correction was not able to positively influence the collapsing parasol deformity in SMA children. There was no increase in RVA especially of the more affected convex side directly after surgical intervention, after nearly 5 years of GFSI treatment and after implant removal. Also, in age- and disease-matched groups with and without prior treatment, no differences were seen. Again, these findings are in line with Livingston et al. [6], who did not find any thoracic deformity changes or differences analyzing rib-based in comparison to spine-based GFSI. When directly comparing treatment of SMA patients either by only GFSI or by combined treatment with GFSI and lateral chest wall support using transverse bars and rib cradles, however, Swarup et al. [24] demonstrated that GFSI combined with lateral chest wall support provided significantly better outcomes in hemithorax width compared to patients without chest wall support. According to our data, the hypothesis that GFSI with a cranial rib anchor raises the ribs to a more normal position and thus enlarge the thorax could not be validated. Consequently, thoracic and lung volumes were not influenced or changed by GFSI treatment.

One limitation of this study is a small sample size and a further reduction of n-numbers due the limited availability of CT images displaying full thoracic and lung volumes and due to extreme rotation of some vertebrae that did not allow to measure corresponding RVA. Measurements of RVA and RVAD are known to come with a certain error due to inter- and intra-observer variability [25, 26]. Inaccuracy of radiographic RVA measurements is especially an obstacle in severe scoliosis with spinal rotation. Several studies focus on this problem [27, 28] and alternative measurements for parasol rib deformity have been postulated [6]. A further limitation of this study is that thoracic and lung volume data cannot be directly related to lung function. This study lacks reliable lung function data to clearly identify the effect of GFSI on lung function in SMA patients.

We thank the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD).

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Institutional Ethics Committee of University Medical Center Göttingen approved the study (reference number 20/4/21). As retrospective radiographic and CT images were used, the Institutional Ethics Committee waived the need for informed consent.

All authors declare to have no conflict of interest.

No funding was received to assist with the preparation of this manuscript.

Initiation of the idea and design of the study: Anna K. Hell; recruitment of participants: Anna K. Hell, Konstantinos Tsaknakis, and Heiko Lorenz; acquisition of data: Julia Austein, Friederike Austein, Konstantinos Tsaknakis, and Heiko M. Lorenz; major contributors in analyzing the data and doing statistical analysis: Katja A. Lüders, Julia Austein, Friederike Austein, and Lena Braunschweig; authors of initial draft: Anna K. Hell, Lena Braunschweig, and Katja A. Lüders; all authors gave final approval and agreed to be accountable for all aspects of the work.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.