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

INTRODUCTION: Children with spinal muscular atrophy (SMA) and progressive neuromuscular scoliosis often require early growth-friendly spinal implant (GFSI) treatment for deformity correction with implant fixation either through pedicle screws or bilateral to the spine using ribto pelvis fixation. It has been proposed that the latter fixation may change the collapsing parasol deformity via changes in the rib-vertebral angle (RVA) with a positive effect on thoracic and lung volume. The purpose of this study was to analyze the effect of paraspinal GFSI with bilateral rib-to-pelvis fixation on the parasol deformity, RVA, thoracic, and lung volumes. METHODS: SMA children with (n = 19) and without (n = 18) GFSI treatment were included. Last follow-up was before definite spinal fusion at puberty. Scoliosis and kyphosis angles, parasol deformity, and index, as well as convex and concave RVA, were measured on radiographs, whereas computed tomography images were used to reconstruct thoracic and lung volumes. RESULTS: In all SMA children (n = 37; with or without GFSI), convex RVA was smaller than concave values at all times. GFSI did not crucially influence the RVA over the 4.6-year follow-up period. Comparing age- and disease-matched adolescents with and without prior GFSI, no effect of GFSI treatment could be detected on either RVA, thoracic, or lung volumes. Parasol deformity progressed over time despite GFSI. CONCLUSION: Despite different expectations, implantation of GFSI with bilateral rib-to-pelvis fixation did not positively influence parasol deformity, RVA and/or thoracic, and lung volumes in SMA children with spinal deformity directly and over time.

Scoliosis Treatment With Growth-Friendly Spinal Implants (GFSI) Relates to Low Bone Mineral Mass in Children With Spinal Muscular Atrophy.

BACKGROUND: Children with spinal muscular atrophy (SMA) frequently develop neuromuscular scoliosis at an early age, requiring surgical treatment with growth-friendly spinal implants (GFSI), such as magnetically controlled growing rods. This study investigated the effect of GFSI on the volumetric bone mineral density (vBMD) of the spine in SMA children. METHODS: Seventeen children (age 13.2±1.2 y) with SMA and GFSI-treated spinal deformity were compared with 25 scoliotic SMA children (age 12.9±1.7 y) without prior surgical treatment as well as age-matched healthy controls (n=29; age 13.3±2.0). Clinical, radiologic, and demographic data were analyzed. For the calculation of the vBMD Z-scores of the thoracic and lumbar vertebrae, phantom precalibrated spinal computed tomography scans were analyzed using quantitative computed tomography (QCT). RESULTS: Average vBMD was lower in SMA patients with GFSI (82.1±8.4 mg/cm 3) compared with those without prior treatment (108.0±6.8 mg/cm 3 ). The difference was more prominent in and around the thoracolumbar region. The vBMD of all SMA patients was significantly lower in comparison with healthy controls, especially in SMA patients with previous fragility fractures. CONCLUSIONS: The results of this study support the hypothesis of reduced vertebral bone mineral mass in SMA children with scoliosis at the end of GFSI treatment in comparison with SMA patients undergoing primary spinal fusion. Improving vBMD through pharmaceutical therapy in SMA patients could have a beneficial effect on the surgical outcome of scoliosis correction while reducing complications. LEVEL OF EVIDENCE: Therapeutic Level III.

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.

Foot Typology, Dynamic and Static Weight Distribution, and Radiographic Changes After Subtalar Arthroereisis in Juvenile Symptomatic Flexible Flat Feet.

Flexible flatfoot is among the most common skeletal disorders in childhood. This study describes the dynamic and static correction effects of subtalar arthroereisis in adolescents with flexible symptomatic flatfeet in comparison to normal subjects as well as to results before and after removal of metal. Eighteen adolescents with 25 symptomatic flexible flatfeet were treated surgically with a subtalar arthroereisis at a mean of 12.5 (10-16) years. At follow-up (mean 3.9 years, range 0.4-8), patients filled out the American Orthopaedic Foot and Ankle Society questionnaire, received radiographs and were examined using dynamic and static pedobarography as well as static hindfoot axis examination. Results were compared to healthy controls (n = 13; 26 feet). Surgically treated feet (n = 25) had better questionnaire results after surgery than before, but lower scores than healthy feet. Radiological parameters improved significantly after surgery. Removal of metal did not influence post-surgical results (follow-up 2.8 years). Surgically treated feet had larger contact areas than normal feet with predominance to the midfoot region. The relative maximum force, relative peak pressure and contact time were higher in the midfoot of treated feet compared to controls. When comparing pedobarography data of treated versus untreated feet of the same patients (subgroup n = 11 feet), there were no differences. Subtalar arthroereisis was able to effectively treat symptomatic flexible flatfeet in this population. Results improved significantly evaluating a questionnaire, radiographs, dynamic and static weight distribution, but were still worse than results of healthy feet. There was no relapse after removal of metal.

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.

Spontaneous humeral torsion deformity correction after displaced supracondylar fractures in children.

BACKGROUND: After displaced supracondylar humerus fractures (SCHF) in children, residual deformities are common with cubitus varus (CV) being the clinically most visible. Distal fragment malrotation may lead to instability, fragment tilt and subsequent CV. Detection and assessment of malrotation is difficult and the fate of post-traumatic humeral torsion deformity is unknown. The aim of this study was to evaluate the incidence of humeral torsion differences in children with surgically treated SCHF and to observe spontaneous changes over time. METHODS: A cohort of 27 children with displaced and surgically treated SCHF were followed prospectively from the diagnosis until twelve months after trauma. Clinical, photographic, sonographic and radiological data were obtained regularly. Differences in shoulder and elbow motion, elbow axis, sonographic humeral torsion measurement and radiological evaluation focusing on rotational spur were administered. RESULTS: Six weeks after trauma, 67% of SCHF children had a sonographically detected humeral torsion difference of > 5° (average 14.0 ± 7.6°). Of those, 44% showed a rotational spur, slight valgus or varus on radiographs. During follow-up, an average decrease of the difference from 14° (six weeks) to 7.8° (four months) to 6.5° (six months) and to 4.9° (twelve months) was observed. The most significant correction of posttraumatic humeral torsion occurred in children < 5 years and with internal malrotation > 20°. CONCLUSION: After displaced and surgically treated SCHF, most children had humeral torsion differences of both arms. This difference decreased within one year after trauma due to changes on the healthy side or correction in younger children with severe deformity. LEVEL OF EVIDENCE/CLINICAL RELEVANCE: Therapeutic Level IV.

[The influence of backpack weight in school children: gait, muscle activity, posture and stability]. / Einfluss des Schulrucksackgewichtes bei Grundschulkindern: Gang, Muskelaktivität, Haltung und Stabilität.

BACKGROUND: Wearing a school backpack every day may cause postural problems and affect the gait pattern of children and adolescents. The aim of the present study was to analyze the influence of a 4 kg backpack load on the gait pattern and postural sway. OBJECTIVES: The aim of the present study was to analyze the influence of a backpack load of 4 kg on the gait and postural sway of elementary school children. MATERIAL AND METHODS: In this prospective study, a group of 12 elementary school children aged between 7 and 10 years without neurological or orthopedic problems participated. The measurements included a clinical examination, three-dimensional gait analysis with electromyographic recordings and measurement of postural sway on a force plate. RESULTS: The backpack load, on average 15% of the body weight, led to a slower walking speed, shorter step length and increased double-support phase. Increased anterior pelvic and trunk tilt, as well as hip flexion were also observed. Furthermore, the muscle activity and postural sway of the children were affected by the increased load. CONCLUSIONS: School backpacks weighing 4 kg caused changes in gait, muscle activity, posture and stability in elementary school children. Due to the weight of the backpack, the centre of mass shifted backwards and the children became less stable. During gait, this was compensated by increased anterior pelvic and trunk tilt and increased hip flexion. The activity of the paraspinal muscles was decreased and indicates that the backpack is carried passively. This may cause a negative long-term effect.

[Claims and realities of brace treatment : Primary correction of scoliosis in children and adolescents]. / Anspruch und Wirklichkeit bei der Korsettbehandlung : Primärkorrektur bei Skoliosen im Kindes- und Jugendalter.

BACKGROUND: It is understood that an effective brace therapy requires a primary curve angle reduction of 50% after administering the first orthotic brace. OBJECTIVES: The aim of the study was to determine the efficacy of conservative brace therapy for scoliosis with a curve angle above 20° and to determine possible influencing factors. MATERIALS AND METHODS: The current study included a cohort of 110 scoliosis patients with conservative brace therapy. The development of the scoliotic curve during brace therapy was documented for an average of 40 months. Influencing factors such as the initial Risser sign, age at the start of treatment, gender, curve patterns and body mass index were analyzed. RESULTS: The collective consisted of 88 patients with idiopathic and 22 with neuromuscular spinal deformities. At the beginning of the brace therapy, the average age was 12.2 ± 2.8 years with a mean scoliosis curve angle of 30.4°â€¯± 12.5°. The primary brace reduced the scoliotic curve by 31% to 20.9°. In children and adolescents with lower maturity status, the success of the brace therapy was greater than in patients with a higher Risser sign. In addition, children with obesity had less success during brace therapy than normal- or underweight children. CONCLUSIONS: The initial curvature correction of 50% required for effective brace therapy could only be achieved in one third of the patients. On average, the correction was 31%.

Health-related quality of life in early-onset-scoliosis patients treated with growth-friendly implants is influenced by etiology, complication rate and ambulatory ability.

BACKGROUND: Progressive Early-Onset Scoliosis (EOS) in children may lead to surgical interventions with growth-friendly implants, which require repeated lengthening procedures in order to allow adequate growth. Quality of life was studied using the validated German version of the EOS-Questionnaire (EOSQ-24-G) in surgically treated EOS children with different lengthening modalities. METHODS: EOSQ-24-G and the KINDLR questionnaire were given to families with EOS children who had been treated by either vertical expandable prosthetic titanium rib implants and repetitive lengthening surgeries every 6 months or children who had received a magnetically expansion controlled implant, which was externally lengthened every 3 months. Results were compared according to differences between the two tests, and with possible influencing factors such as surgical method, severity of scoliosis, relative improvement of curvature, etiology, weight, age, travelling distance, complications, ambulatory ability and others. RESULTS: 56 children with an average curve angle of 69° corrected to 33° (52%; average age 5.6 yrs) answered the EOSQ-24-G and the KINDLR after an average follow-up of 3.9 years. Health-related quality of life (HRQoL) was not affected by the initial scoliosis correction, the number of surgeries or the implant type. However, there was a negative correlation with non-ambulatory status, complications during treatment and for children with a neuromuscular scoliosis. CONCLUSION: Using the validated EOSQ-24-G, no statistically significant differences were found between the group of children receiving repetitive surgeries and children with external lengthening procedures without surgery. However, results were influenced by the etiology, complication rate or ambulatory ability. LEVEL OF EVIDENCE/CLINICAL RELEVANCE: Therapeutic Level IV.

High Correlation Between Achieved and Expected Distraction Using Magnetically Controlled Growth Rods (MCGR) With Rib to Pelvis Fixation in Pediatric Spine Deformity.

PURPOSE: Magnetically controlled implant systems have been established to treat severe progressive spinal deformity in children. The purpose of this study was to evaluate (1) the ratio between achieved and expected distraction length, (2) the complication rate and its risk factors as well as (3) the correlation of the distraction length and the length of the spine. METHODS: A total of 40 patients with an average follow-up of 34 (14 to 57) months were prospectively included in the study. Children underwent lengthening procedures every three months. The ratio between the distraction lengths was determined by comparing the measured distraction length of the rod on radiographs with the distraction length displayed on the external remote controller for the magnetically controlled growing rod (MCGR). Age, weight, height, and complications were repeatedly recorded. RESULTS: The analysis of 746 procedures showed the actual distraction to be 94.4% of the expected one. No difference between implants on the concave and convex spinal side was observed. The overall complication rate was 4.6% mainly because of failure of the implant or lack of implant extension, which was directly related to an increased BMI. There was also a strong correlation between achieved implant distraction length and gain in spinal length. CONCLUSIONS: Our study demonstrates a high ratio (0.94) between achieved and expected distraction length of magnetically controlled spinal rods. The complication rate was low (4.6%) and correlated to a high BMI. The correlation between the achieved implant distraction length and spinal length indicates the efficiency of the MCGR therapy. LEVEL OF EVIDENCE: Therapeutic Level IV.

Brain oxygen tension controls the expansion of outer subventricular zone-like basal progenitors in the developing mouse brain.

The mammalian neocortex shows a conserved six-layered structure that differs between species in the total number of cortical neurons produced owing to differences in the relative abundance of distinct progenitor populations. Recent studies have identified a new class of proliferative neurogenic cells in the outer subventricular zone (OSVZ) in gyrencephalic species such as primates and ferrets. Lissencephalic brains of mice possess fewer OSVZ-like progenitor cells and these do not constitute a distinct layer. Most in vitro and in vivo studies have shown that oxygen regulates the maintenance, proliferation and differentiation of neural progenitor cells. Here we dissect the effects of fetal brain oxygen tension on neural progenitor cell activity using a novel mouse model that allows oxygen tension to be controlled within the hypoxic microenvironment in the neurogenic niche of the fetal brain in vivo. Indeed, maternal oxygen treatment of 10%, 21% and 75% atmospheric oxygen tension for 48 h translates into robust changes in fetal brain oxygenation. Increased oxygen tension in fetal mouse forebrain in vivo leads to a marked expansion of a distinct proliferative cell population, basal to the SVZ. These cells constitute a novel neurogenic cell layer, similar to the OSVZ, and contribute to corticogenesis by heading for deeper cortical layers as a part of the cortical plate.

Surgical Treatment of Spinal Deformities in Young Paraplegic Children with Intraspinal Tumors.

Bilateral vertical expandable prosthetic titanium rib (VEPTR) treatment using rib-to-pelvis constructs without touching the spine is a safe surgical technique to correct scoliosis while still allowing further MRI or neurosurgical interventions. In this retrospective cohort study, 4 paraplegic children with spinal deformity after intraspinal tumors and 4 children with neuromuscular diseases were compared. VEPTR treatment was able to considerably reduce the main scoliotic curve in both patient groups (41 vs. 40%). However, the tumor group constantly showed more severe curve progression over time and less favorable pelvic obliquity control. In conclusion, bilateral VEPTR can be expected to be less satisfying in children with tumors.

Oxygen regulates proliferation of neural stem cells through Wnt/ß-catenin signalling.

Reduced oxygen levels (1-5% O2, named herein 'physioxia') are beneficial for stem cell cultures leading to enhanced proliferation, better survival and higher differentiation potential, but the underlying molecular mechanisms remain elusive. A potential link between physioxia and the canonical Wnt pathway was found recently, but the differential involvement of this signalling pathway for the various stem cell properties such as proliferation, stem cell maintenance, and differentiation capacity remains enigmatic. We here demonstrate increased Wnt target gene transcription and stabilised active ß-catenin upon physioxic cell culture in primary tissue-specific foetal mouse neural stem cells. Knock-out of the main oxygen sensing molecule, hypoxia-inducible factor-1α (Hif-1α), had no impact on Wnt activation assuming that physioxia induces the Wnt pathway independently of Hif-1α. To determine the physiological relevance of physioxia-induced Wnt/ß-catenin signalling, we examined proliferation, cell cycle kinetics, survival and stem cell maintenance upon Wnt activation and inhibition. Whereas survival and stem cell maintenance seem to be independent of the Wnt pathway, our studies provide first evidence that Wnt/ß-catenin signalling positively stimulates proliferation of physioxic cells by affecting cell cycle regulation. Together, our results provide mechanistic insight into oxygen-mediated regulation of the self-renewal activity of neural stem cells.

Notch is Not Involved in Physioxia-Mediated Stem Cell Maintenance in Midbrain Neural Stem Cells.

Background and Objectives: The physiological oxygen tension in fetal brains (∼3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1α/Notch regulatory interactions as well as our observations that Hif-1α and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance. Methods and Results: Here we found that physioxia (3% O2) compared to normoxia (21% O2) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions. Conclusions: Notch signalling does not influence the fate decision of midbrain NSCs cultured in vitro in physioxia, where other factors like Hif-1α might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.

Osmotic pump with potential for bone lengthening distracts continuously in vitro and in vivo.

BACKGROUND: In pediatric orthopedics, long bone lengthening procedures are routinely performed using manual, motorized or magnetically controlled implants. This study aims to prove expansion of a newly designed osmotic pump prior to long bone lengthening in living organisms and to rule out any complications related to in vivo conditions, such as congestion of the semipermeable membrane, local infection, or lack of water to drive the osmotic pump, as well as to compare in vivo and in vitro expansion data. METHODS: Osmotic pumps, which were designed to distract a plate osteosynthesis, were inserted in the dorsal paraspinal musculature of four piglets. To compare the performance of the pumps in in vivo and in vitro conditions, another set of pumps was submerged in physiologic saline solution at different temperatures. The lengthening progress was measured radiographically and sonographically in the study animals. RESULTS: Both, in vitro and in vivo tested osmotic pumps started distraction after an intended rest phase of four days and distracted evenly over the following twelve days. No complications, clogging or damages occurred. However, we observed a temperature dependency of the distraction rate ranging from 0.98 mm/day at 39°C to 1.10 mm/day at 42°C. With a second setup, we confirmed that the distraction rate differed by 72% within a measured temperature interval of 14° C. CONCLUSIONS: The data presented here confirm that the novel osmotic pump showed comparable lengthening characteristics in vivo and in vitro. No complications, such as congestion of the semipermeable membrane, local infection, or lack of water to drive the osmotic pump were observed. Thus, osmotic pumps may have great potential in future applications such as long bone lengthening procedures, where continuous distraction probably provides a better bone quality than intermittent lengthening procedures. The fact that one pump failed to elongate in each condition, highlights the importance of technical improvement, but also demonstrates that this was not due to different circumstances within the in vivo or in vitro condition.

Serial Gene Expression Profiling of Neural Stem Cells Shows Transcriptome Switch by Long-Term Physioxia from Metabolic Adaption to Cell Signaling Profile.

Oxygen is an essential factor in the cellular microenvironment with pivotal effects on neural development with a particular sensitivity of midbrain neural stem cells (NSCs) to high atmospheric oxygen tension. However, most experiments are still performed at atmospheric O2 levels (21%, normoxia), whereas mammalian brain tissue is physiologically exposed to substantially lower O2 tensions around 3% (physioxia). We here performed serial Affymetrix gene array analyses to detect expression changes in mouse fetal NSCs from both midbrain and cortical tissues when kept at physioxia compared to normoxia. We identified more than 400 O2-regulated genes involved in cellular metabolism, cell proliferation/differentiation, and various signaling pathways. NSCs from both regions showed a low number but high conformity of regulated genes (9 genes in midbrain vs. 34 in cortical NSCs; 8 concordant expression changes) after short-term physioxia (2 days) with metabolic processes and cellular processes being the most prominent GO categories pointing to cellular adaption to lower oxygen levels. Gene expression profiles changed dramatically after long-term physioxia (13 days) with a higher number of regulated genes and more diverse expression patterns when comparing the two NSC types (338 genes in midbrain vs. 121 in cortical NSCs; 75 concordant changes). Most prominently, we observed a reduction of hits in metabolic processes but an increase in biological regulation and signaling pointing to a switch towards signaling processes and stem cell maintenance. Our data may serve as a basis for identifying potential signaling pathways that maintain stem cell characteristics in cortical versus midbrain physioxic stem cell niches.

Limited trunk motion and posterior pelvic tilting in ambulatory children treated with bilateral rib to pelvis implants for spinal deformity control.

In young children, growth-friendly spinal implants with bilateral rib to pelvis fixation are used to control progressive spinal deformity. Whereas curve progression, complications and side-effects have been extensively studied in this patient population, no data are available on gait pattern changes and postural body adjustments. Our study evaluates whether gait pattern changed for ambulatory children treated with bilateral rib to pelvis implants compared to age-matched healthy children. In this small cohort study, gait analysis was performed using spatiotemporal and kinematic parameters of four ambulatory children with severe scoliosis and growth-friendly spinal implants using the bilateral rib to pelvis fixation. Data were statistically analyzed and compared to seven healthy age-matched children. Between both groups, no differences were seen in walking speed, cadence and stride length. The treated patients showed a lower range of motion of the pelvic obliquity and of the trunk obliquity and rotation, but a higher knee flexion. Growth-friendly spinal implants with bilateral rib to pelvis fixation are commonly used in wheelchair children and rarely indicated in ambulatory patients. The presented data show reduced trunk and pelvis motion using this implant construct. These findings help to understand body postural adjustments and add valuable information for families and care providers when considering this surgery. Level of evidence: Therapeutic level IV.

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.

Reduced Volumetric Bone Mineral Density of the Spine in Adolescent Rett Girls with Scoliosis.

In advanced Rett syndrome (RTT), limited or complete loss of ambulation, nutritional problems and scoliosis are unfavorable factors for bone mineral density (BMD). Still, there are few data available in this research area. Spinal quantitative computed tomography (QCT) allows an exact measurement of the volumetric BMD (vBMD) in this patient group. Two examiners measured vBMD of thoracic and lumbar vertebrae on asynchronous calibrated CTs that were acquired prior to surgical scoliosis correction (n = 21, age 13.6 ± 2.5 years). The values were compared to age- and sex-matched healthy controls to additionally derive Z-scores (n = 22, age 13.8 ± 2.0 years). The results showed the most significant reduction of vBMD values in non-ambulatory RTT patients, with p < 0.001 and average BMD-Z-score −1.5 ± 0.2. In the subgroup comparison, non-ambulatory patients with valproate treatment had significant lower values (p < 0.001) than ambulatory patients without valproate therapy, with an average BMD-Z-score of −2.3 ± 0.2. Comparison of the Z-scores to critical BMD thresholds of 120 and 80 mg/cm3 showed normal Z-scores in case of the ambulatory RTT subgroup, as opposed to BMD-Z-scores of the non-ambulatory RTT subgroups, which were partially below osteopenia-equivalent values. Furthermore, valproate treatment seems to have a direct effect on vBMD in RTT patients and when combined with loss of ambulation, BMD-Z-scores are reduced to osteoporosis-equivalent levels or even further.