Children with Spinal Muscular Atrophy Have Reduced Vertebral Body Height and Depth and Pedicle Size in Comparison to Age-Matched Healthy Controls.

BACKGROUND: Most children with spinal muscular atrophy (SMA) develop spinal deformity, which may require surgical intervention. In addition to poor bone stock, vertebral body shape may hinder the placement of spinal implants resulting in complications and poor outcome. The aim of this study was to analyze whether vertebral body morphology of children and adolescents with SMA is altered in comparison to healthy age-matched controls. METHODS: In this prospective cohort study, 17 children with SMA (mean age 8.7 ±1.0 years) and 13 adolescents with SMA (mean age 13.6 ±1.4 years), all with some degree of neuromuscular scoliosis, were analyzed by standardized radiographic measurements to evaluate vertebral body height and depth. Results were compared with age-matched healthy controls (n = 10 children; mean age 9.1 ± 1.6 years; n = 20 adolescents, mean age 13.1 ± 0.5 years). Computed tomography scans of 27 adolescents with SMA (13.5 ±1.2 years) and 25 healthy age-matched controls (13.8 ±2.0 years) were analyzed to define pedicle diameters. RESULTS: All children and adolescents with SMA had decreased vertebral height and depth in comparison to age-matched healthy controls. In adolescents, reduced depth was more pronounced than height in the thoracic spine. Pedicle size was significantly reduced in the lower thoracic and lumbar area. CONCLUSIONS: Reduced vertebral body height and depth and pedicle size in children and adolescents with SMA may influence surgical treatment of spinal deformity. Surgeons should be aware of anatomical differences and choose implant devices accordingly.

Vertebral body changes after continuous spinal distraction in scoliotic children.

PURPOSE: Growth-friendly spinal implants (GFSI) were established for scoliotic children as an interim solution until definite spinal fusion could be performed during puberty. While deformity control was clearly proven, the effects on vertebral shape and morphology are still unclear. Our prospective study assesses the effect of GFSI with continuous distraction on vertebral body shape and volume in SMA children in comparison with previously untreated age-matched SMA patients. METHODS: Cohort I (n = 19, age 13.2 years) were SMA patients without prior surgical scoliosis treatment. Cohort II (n = 24, age 12.4 years) were children, who had continuous spinal distraction with GFSI for 4.5 years. Radiographic measurements and computed tomography (CT) 3D volume rendering were performed before definite spinal fusion. For cohort II, additional radiographs were analyzed before the first surgical implantation of GFSI, after surgery and every year thereafter. RESULTS: Our analysis revealed decreased depth and volume in scoliotic patients with prior GFSI compared to scoliotic patients without prior implants. This difference was significant for the lower thoracic and entire lumbar spine. Vertebral body height and pedicle size were unchanged between the two cohorts. CONCLUSION: CT data showed volume reduction in the vertebral body in scoliotic children after GFSI treatment. This effect was more severe in the lumbar and lower thoracic area. While vertebral height was identical in both groups, vertebral depth was reduced in the GFSI-treated group. Reduced vertebral depth and altered vertebral morphology should be considered before instrumenting the spine in previously treated scoliotic SMA children. LEVEL OF EVIDENCE III: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Altered bone development with impaired cartilage formation precedes neuromuscular symptoms in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a fatal neurodegenerative disease of newborns and children caused by mutations or deletions of the survival of motoneuron gene 1 resulting in low levels of the SMN protein. While neuromuscular degeneration is the cardinal symptom of the disease, the reduction of the ubiquitously expressed SMN additionally elicits non-motoneuron symptoms. Impaired bone development is a key feature of SMA, but it is yet unknown whether this is an indirect functional consequence of muscle weakness or caused by bone-intrinsic mechanisms. Therefore, we radiologically examined SMA patients in a prospective, non-randomized cohort study characterizing bone size and bone mineral density (BMD) and performed equivalent measurements in pre-symptomatic SMA mice. BMD as well as lumbar vertebral body size were significantly reduced in SMA patients. This growth defect but not BMD reduction was confirmed in SMA mice by µCT before the onset of neuromuscular symptoms indicating that it is at least partially independent of neuromuscular degeneration. Interestingly, the number of chondroblasts in the hypertrophic zone of the growth plate was significantly reduced. This was underlined by RNAseq and expression data from developing SMA mice vertebral bodies, which revealed molecular changes related to cell division and cartilage remodeling. Together, these findings suggest a bone intrinsic defect in SMA. This phenotype may not be rescued by novel drugs that enhance SMN levels in the central nervous system only.