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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.
Subject(s)
Bone Lengthening , Orthopedics , Animals , Swine , Osmosis , Bone Plates , WaterABSTRACT
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.
Subject(s)
Muscular Atrophy, Spinal , Scoliosis , Spinal Fusion , Adolescent , Humans , Child , Scoliosis/diagnostic imaging , Scoliosis/surgery , Treatment Outcome , Lung Volume Measurements , Muscular Atrophy, Spinal/diagnostic imaging , Muscular Atrophy, Spinal/surgery , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Ribs/diagnostic imaging , Ribs/surgery , Spinal Fusion/methodsABSTRACT
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.
Subject(s)
Muscular Atrophy, Spinal , Scoliosis , Spinal Fusion , Humans , Child , Adolescent , Scoliosis/diagnostic imaging , Scoliosis/etiology , Scoliosis/surgery , Treatment Outcome , Muscular Atrophy, Spinal/surgery , Muscular Atrophy, Spinal/complications , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Bone Density , Spinal Fusion/methodsABSTRACT
Background and Objectives: The physiological oxygen tension in fetal brains (â¼3%, 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.
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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.
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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.
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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.
Subject(s)
Muscular Atrophy, Spinal , Scoliosis , Spinal Fusion , Adolescent , Child , Humans , Muscular Atrophy, Spinal/complications , Muscular Atrophy, Spinal/diagnostic imaging , Muscular Atrophy, Spinal/surgery , Prospective Studies , Scoliosis/complications , Scoliosis/diagnostic imaging , Scoliosis/surgery , Spinal Fusion/methods , Spine/diagnostic imaging , Spine/surgery , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Vertebral BodyABSTRACT
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.
Subject(s)
Flatfoot , Orthopedic Procedures , Subtalar Joint , Adolescent , Flatfoot/diagnostic imaging , Flatfoot/surgery , Foot/diagnostic imaging , Foot/surgery , Humans , Orthopedic Procedures/methods , Radiography , Subtalar Joint/diagnostic imaging , Subtalar Joint/surgery , Treatment OutcomeABSTRACT
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.
Subject(s)
Scoliosis , Biomechanical Phenomena , Child , Child, Preschool , Cohort Studies , Gait , Humans , Pelvis/diagnostic imaging , Pelvis/surgery , Ribs/diagnostic imaging , Ribs/surgery , Scoliosis/diagnostic imaging , Scoliosis/surgery , SpineABSTRACT
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.
Subject(s)
Elbow Joint , Humeral Fractures , Child , Elbow Joint/diagnostic imaging , Elbow Joint/surgery , Humans , Humeral Fractures/complications , Humeral Fractures/diagnostic imaging , Humeral Fractures/surgery , Humerus/diagnostic imaging , Torsion Abnormality , UltrasonographyABSTRACT
In recent decades, magnetically controlled growing rods (MCGR) were established to treat progressive early-onset scoliosis. The aim of this investigation was to assess the effect of long-term MCGR with continuous distraction on intervertebral discs in scoliotic children. Magnetic resonance imaging (MRI) of 33 children with spinal muscular atrophy was analyzed by grading intervertebral disc degeneration (IDD) and measuring intervertebral disc volume. Cohort I (n = 17) were children who had continuous spinal distraction with MCGRs for 5.1 years and MRI before (av. age 8.1) and after (av. age 13.4) MCGR treatment. Cohort II (n = 16, av. age 13.7) were patients without prior surgical treatment. Lumbar intervertebral disc volume of cohort I did not change during 5.1 years of MCGR treatment, whereas disc volumes were significantly larger in age- and disease-matched children without prior treatment (cohort II). Cohort I showed more IDD after MCGR treatment in comparison to early MRI studies of the same patients and children without surgical treatment. MRI data showed a volume reduction and disc degeneration of lower thoracic and lumbar intervertebral discs in scoliotic children after continuous spinal distraction with MCGRs. These effects were confirmed in the same subjects before and after treatment as well as in surgically untreated controls.
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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.
Subject(s)
Scoliosis , Vertebral Body , Adolescent , Child , Cross-Sectional Studies , Humans , Prospective Studies , Scoliosis/diagnostic imaging , Scoliosis/surgery , Thoracic VertebraeABSTRACT
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 4â¯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 4â¯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.
Subject(s)
Gait , Posture , Adolescent , Biomechanical Phenomena , Body Weight , Child , Humans , Muscles , Prospective Studies , Schools , Walking , Weight-BearingABSTRACT
Childhood tumors of the central nervous system (CNS) and other entities affecting the spine are rare. Treatment options vary from surgical biopsy to partial, subtotal, and total resection, to radiation, to chemotherapy. The aim of this study is to investigate spinal deformity and subsequent surgical interventions in this patient cohort. A retrospective review at our institution identified children with CNS tumors, spinal tumors, and juxta-spinal tumors, as well as spinal deformities. Tumor entity, treatment, mobilization, and radiographic images were analyzed relative to the spinal deformity, using curve angles in two planes. Conservative or surgical interventions such as orthotic braces, growth-friendly spinal implants, and spinal fusions were evaluated and analyzed with respect to treatment results. Tumor entities in the 76 patients of this study included CNS tumors (n = 41), neurofibromatosis with spinal or paraspinal tumors (n = 14), bone tumors (n = 12), embryonal tumors (n = 7), and others (n = 2). The initial treatment consisted of surgical biopsy (n = 5), partial, subtotal, or total surgical resection (n = 59), or none (n = 12), followed by chemotherapy, radiotherapy, or both (n = 40). Out of 65 evaluated patients, 25 revealed a moderate or severe scoliotic deformity of 71° (range 21-116°), pathological thoracic kyphosis of 66° (range 50-130°), and lordosis of 61° (range 41-97°). Surgical treatment was performed on 21 patients with implantation of growth-friendly spinal implants (n = 9) as well as twelve dorsal spinal fusions (two with prior halo distraction). Surgical interventions significantly improved spinal deformities without additional neurological impairment. With the increasing number of children surviving rare tumors, attention should be focused on long-term problems such as spinal deformities and consequent disabilities. A significant number of children with CNS tumors, spinal tumors or juxta-spinal tumors required surgical intervention. Early information about spinal deformities and a close follow-up are mandatory for this patient group.
ABSTRACT
Magnetically controlled growing rods (MCGR) are commonly implanted for the treatment of early-onset scoliosis. While most authors report favorable short-term results, little is known about long-term deformity correction. This prospective cohort study assesses spinal deformity control in a homogeneous spinal muscular atrophy (SMA) patient group treated with MCGR implants, a standardized lengthening protocol and a minimum follow-up of four years. 17 SMA patients with progressive scoliosis were treated with MCGR implanted parallel to the spine with rib-to-pelvis fixation. Radiologic measurements were performed before and after MCGR implantation and during external lengthening procedures. These included measurements of the scoliotic curve, kyphosis, lordosis, pelvic obliquity and the spinal length. Additional clinical data of the complications were also analyzed. 17 children (mean age 7.4 years) were surgically treated and underwent a total of 376 lengthenings. Complication rates were 3.5% in respect to all interventions or 41% of the patients had complications during 3.5% of the lengthening sessions. The initial implantation significantly reduced the main scoliotic curve by 59%, with the correction remaining constant throughout the follow-up. Pelvic obliquity was also significantly and permanently corrected by 72%, whereas kyphosis and lordosis were not influenced. The spinal length could be significantly increased mostly during the first year of treatment. Bilateral implantation of MCGRs for correction of spinal deformity in children with SMA showed no decrease of the lengthening potential during a four-year follow-up. Therefore, the previously described 'law of diminishing returns' could not be applied to this patient population.Level of Evidence/Clinical relevance: Therapeutic Level IV.
Subject(s)
Bone Lengthening/instrumentation , Muscular Atrophy, Spinal/surgery , Spinal Curvatures/surgery , Bone Lengthening/methods , Child , Child, Preschool , Cohort Studies , Female , Humans , Internal Fixators , Kyphosis/etiology , Kyphosis/pathology , Kyphosis/surgery , Lordosis/etiology , Lordosis/pathology , Lordosis/surgery , Magnetics , Male , Muscular Atrophy, Spinal/complications , Muscular Atrophy, Spinal/pathology , Pelvis/surgery , Prospective Studies , Prostheses and Implants , Ribs/surgery , Scoliosis/etiology , Scoliosis/pathology , Scoliosis/surgery , Spinal Curvatures/etiology , Spinal Curvatures/pathology , Treatment OutcomeABSTRACT
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.
Subject(s)
Bone Development/genetics , Motor Neurons/metabolism , Muscular Atrophy, Spinal/genetics , Neurodegenerative Diseases/genetics , Survival of Motor Neuron 1 Protein/genetics , Adolescent , Animals , Bone Density/genetics , Cartilage/growth & development , Cartilage/pathology , Central Nervous System/metabolism , Central Nervous System/pathology , Child , Chondrocytes/metabolism , Chondrocytes/pathology , Disease Models, Animal , Female , Humans , Male , Mice , Motor Neurons/pathology , Muscular Atrophy, Spinal/diagnostic imaging , Muscular Atrophy, Spinal/pathology , Nerve Degeneration/genetics , Nerve Degeneration/pathology , Neurodegenerative Diseases/diagnostic imaging , Neurodegenerative Diseases/pathology , PhenotypeABSTRACT
BACKGROUND: Almost all children with spinal muscular atrophy (SMA) develop a scoliosis during childhood and adolescence. In the last decades, growth-friendly spinal implants have been established as an interim solution for these patients until definite spinal fusion can be performed. The effect of those implants on the final outcome has yet to be described. OBJECTIVE: To assess the effect of prior growth-friendly spinal surgical treatment on the outcome after spinal fusion in SMA children in comparison to untreated SMA patients through the prospective study. METHODS: A total of 28 SMA patients with (n = 14) and without (n = 14) prior surgical treatment with growth-friendly implants were included. Average surgical treatment prior to definite spinal fusion was 4.9 yr. Scoliotic curve angle, pelvic obliquity, spinal length, kyphosis, and lordosis were evaluated for children with prior treatment and before and after dorsal spondylodesis for all children. RESULTS: The curve angle before definite spinal fusion averaged at 104° for SMA patients without prior treatment and 71° for patients with prior treatment. Spondylodesis reduced the scoliotic curve to 50° and 33°, respectively, which equals a correction of 52% vs 54%. Pelvic obliquity could be improved by spinal fusion in all patients with better results in the pretreated group. Results for spinal length, kyphosis, and lordosis were similar in both groups. CONCLUSION: These data show the positive effect of prior growth-friendly surgical treatment on radiographic results of spinal fusion in children with SMA. Both scoliotic curve angles and pelvic obliquity showed significantly better values when patients had growth-friendly implants before definite spinal fusion.
Subject(s)
Muscular Atrophy, Spinal/complications , Orthopedic Procedures/instrumentation , Prostheses and Implants , Scoliosis/etiology , Scoliosis/surgery , Spinal Fusion/methods , Adolescent , Child , Female , Humans , Male , Orthopedic Procedures/methods , Treatment OutcomeABSTRACT
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%.
Subject(s)
Scoliosis/therapy , Adolescent , Braces , Child , Cohort Studies , Conservative Treatment , Humans , Treatment OutcomeABSTRACT
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.
Subject(s)
Bone Lengthening/instrumentation , Child Development , Prostheses and Implants , Quality of Life , Scoliosis/surgery , Age of Onset , Ambulatory Care/statistics & numerical data , Bone Lengthening/methods , Bone Lengthening/statistics & numerical data , Child , Child, Preschool , Female , Follow-Up Studies , Health Services Accessibility/statistics & numerical data , Humans , Male , Reoperation/statistics & numerical data , Scoliosis/complications , Surveys and Questionnaires/statistics & numerical data , Treatment OutcomeABSTRACT
OBJECTIVE: During childhood, early-onset scoliosis (EOS) may show severe progressive deformity, which consequently leads to aggressive treatment strategies, such as serial casting, long-term bracing, or surgical interventions. The latter usually includes repeated surgeries for implant lengthening every 6 months in order to allow sufficient growth of the thorax and spine. In 2011, the 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24) was introduced to measure health-related quality of life for this patient group and their families. Since then, cross-culturally adapted versions of the EOSQ-24 have been published in Spanish, Turkish, traditional Chinese, and Norwegian. The purpose of the study was to transculturally adapt the original English version of the EOSQ-24 into the German language and evaluate the reliability of the German version. METHODS: After adaptation and forward/backward translation, the German version of the EOSQ-24 was given to the parents or caregivers of 67 EOS patients (33 male, 34 female) Data quality was evaluated by mean, standard deviation, percentage of data missing, and extent of ceiling and floor effects. Reliability was estimated by internal consistency using Cronbach α and item-total correlations. RESULTS: In the study group (n = 67), 12 children were either observed (n = 7) or treated with a brace (n = 5). The other 55 patients were treated surgically with growth-friendly implants. The item response to the German EOSQ-24 was high with a minimum of missing data (1.7%). All items showed very good to excellent internal consistencies (0.879-0.903). Floor effects for the 24 items were between 0% and 31% and ceiling effects between 9% and 78%. The calculated Cronbach α for the 24-item scale was 0.9003, indicating excellent reliability. CONCLUSIONS: The German adaptation of the EOSQ-24 shows excellent reliability and therefore is a valid tool to measure objective health-related quality of life in children with EOS.