Scoliosis Development in Spinal Muscular Atrophy: The Influences of Genetic Severity, Functional Level, and Disease-Modifying Treatments.

BACKGROUND: Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to deficiency in SMN protein and loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes, including nusinersen and gene replacement therapies, have improved gross motor and respiratory function, but their impact on scoliosis development has not been established. This study aimed to determine risk factors for scoliosis development in SMA, specifically genetic severity and DMA use. METHODS: In this retrospective cohort study, children with SMA and minimum 2-year follow-up were included. The primary outcome was the prevalence of clinically relevant scoliosis. Secondary outcomes included SMA type, SMN2 copy number, Hammersmith Functional Motor Scale (HFMS), ambulatory status [functional mobility scale at 50m (FMS 50 )], DMA use, and hip displacement as risk factors. Univariate/multivariate logistic regression analyses were performed to identify dependent/independent risk factors. RESULTS: One hundred sixty-five patients (51% female) with SMA types I-III met the inclusion criteria, with total follow-up of 9.8 years. The prevalence of scoliosis was 79%; age of onset 7.9 years. The major curve angle for the entire cohort at first assessment and final follow-up was 37 degrees (SD: 27 degrees) and 62 degrees (SD: 31 degrees) ( P <0.0001), respectively. Significant risk factors for scoliosis by univariate analysis were SMA type (I/II, P =0.02), HFMS (>23, P <0.001), nonambulatory status (FMS 50 =1, P <0.0001), DMA treatment ( P =0.02), and hip displacement ( P <0.0001). Multivariate analysis revealed that HFMS >23 ( P =0.02) and DMA ( P =0.05) treatment were independent (protective) risk factors. CONCLUSIONS: The development of scoliosis in SMA is high, with risk factors associated with proxy measures of disease severity, including SMA type, nonambulatory status, hip displacement, and most notably, gross motor function (by HFMS). DMA use and HFMS >23 were associated with a decreased risk of scoliosis development. Identified risk factors can be used in the development of surveillance programs for early detection of scoliosis in SMA. LEVEL OF EVIDENCE: Level III.

Incidence of Tether Breakage in Anterior Vertebral Body Tethering.

BACKGROUND: Thoracic anterior vertebral body tethering (TAVBT) is an emerging treatment for adolescent idiopathic scoliosis. Tether breakage is a known complication of TAVBT with incompletely known incidence. We aim to define the incidence of tether breakage in patients with adolescent idiopathic scoliosis who undergo TAVBT. The incidence of tether breakage in TAVBT is hypothesized to be high and increase with time postoperatively. METHODS: All patients with right-sided, thoracic curves who underwent TAVBT with at least 2 and up to 3 years of radiographic follow-up were included. Tether breakage between 2 vertebrae was defined a priori as any increase in adjacent screw angle >5 degrees from the minimum over the follow-up period. The presence and timing of tether breakage were noted for each patient. A Kaplan-Meier survival analysis was performed to calculate expected tether breakage up to 36 months. χ 2 analysis was performed to examine the relationship between tether breakage and reoperations. Independent t test was used to compare the average final Cobb angle between cohorts. RESULTS: In total, 208 patients from 10 centers were included in our review. Radiographically identified tether breakage occurred in 75 patients (36%). The initial break occurred at or beyond 24 months in 66 patients (88%). Kaplan-Meier survival analysis estimated the cumulative rate of expected tether breakage to be 19% at 24 months, increasing to 50% at 36 months. Twenty-one patients (28%) with a radiographically identified tether breakage went on to require reoperation, with 9 patients (12%) requiring conversion to posterior spinal fusion. Patients with a radiographically identified tether breakage went on to require conversion to posterior spinal fusion more often than those patients without identified tether breakage (12% vs. 2%; P =0.004). The average major coronal curve angle at final follow-up was significantly larger for patients with radiographically identified tether breakage than for those without tether breakage (31 deg±12 deg vs. 26 deg±12 deg; P =0.002). CONCLUSIONS: The incidence of tether breakage in TAVBT is high, and it is expected to occur in 50% of patients by 36 months postoperatively. LEVEL OF EVIDENCE: Level IV.

Operative differences for posterior spinal fusion after vertebral body tethering: Are we fusing more levels in the end?

PURPOSE: Little is known about the perioperative characteristics associated with a posterior spinal fusion (PSF) in adolescent idiopathic scoliosis patients previously treated with vertebral body tethering (VBT). We aimed to determine if operative time, estimated blood loss, postoperative length of stay, instrumentation type, and implant density differed in patients that received a PSF (i.e., PSF-Only) or a PSF following a failed VBT (i.e., PSF-VBT). METHODS: We retrospectively assessed matched cohort data (PSF-VBT = 22; PSF-Only = 22) from two multi-center registries. We obtained: (1) operative time, (2) estimated blood loss, (3) postoperative length of stay, (4) instrumentation type, and (5) implant density. Theoretical fusion levels prior to the index procedure were obtained for PSF-VBT and compared to the actual levels fused. RESULTS: We observed no difference in operative time, estimated blood loss, or postoperative length of stay. Instrumentation type was all-screw in PSF-Only and varied in PSF-VBT with nearly 25% of patients exhibiting a hybrid construct. There was no added benefit to removing anterior instrumentation prior to fusion; however, implant density was higher in PSF-Only (1.9 ± 0.2) than when compared to PSF-VBT (1.7 ± 0.3). An additional two levels were fused in 50% of PSF-VBT patients, most of which were added to the distal end of the construct. CONCLUSIONS: We found that operative time, estimated blood loss, and postoperative length of stay were similar in both cohorts; however, the length of the fusion construct in PSF-VBT is likely to be two levels longer when a failed VBT is converted to a PSF.

Orthopaedic Manifestations of Transverse Myelitis in Children.

BACKGROUND: Transverse myelitis (TM) is a rare inflammatory disorder of the spinal cord. It can have a heterogeneous presentation with sensory, motor, and autonomic dysfunction. Neurological sequelae of TM include autonomic dysfunction, motor weakness, and/or spasticity. Studies describing orthopaedic deformities and treatments associated with TM are nonexistent. This purpose of this study was to describe the orthopaedic manifestations of TM in children. METHODS: A multicenter retrospective review was conducted of patients, 0 to 21 years of age, with TM presenting over a 15-year period at 4 academic children's hospitals. Those with confirmed diagnosis of TM and referred to an orthopaedic surgeon were included. Demographics, orthopaedic manifestations, operative/nonoperative treatments, and complications were recorded. Descriptive statistics were used for data reporting. RESULTS: Of 119 patients identified with TM, 37 saw an orthopaedic surgeon. By etiology, 23 were idiopathic (62%), 10 infectious (27%), 3 (8%) inflammatory/autoimmune, and 1 (3%) vascular. The mean age at diagnosis was 6.7 (SD: 5.5) years and at orthopaedic presentation was 8.4 (SD: 5.2) years. Orthopaedic manifestations included scoliosis in 13 (35%), gait abnormalities in 7 (19%), foot deformities in 7 (19%), upper extremity issues in 7 (19%), symptomatic spasticity in 6 (16%), lower extremity muscle contractures in 6 (16%), fractures in 6 (16%), hip displacement in 3 (8%), pain in 2 (5%), and limb length discrepancy in 2 (5%) patients. Seven children (19%) were seen for establishment of care. In all, 14 (38%) underwent operative intervention, mainly for soft-tissue and scoliosis management. Four patients had baclofen pump placement for spasticity management. Postoperative complications occurred in 36% of cases, most commonly because of infection. Neither topographic pattern nor location of lesion had a significant relationship with need for hip or spine surgery. CONCLUSIONS: This report describes the orthopaedic manifestations associated with TM in children, nearly 40% of whom required operative intervention(s). Understanding the breadth of musculoskeletal burden incurred in TM can help develop surveillance programs to identify and treat these deformities in a timely manner. LEVEL OF EVIDENCE: Level IV.

Conservation Genomics of the Threatened Western Spadefoot, Spea hammondii, in Urbanized Southern California.

Populations of the western spadefoot (Spea hammondii) in southern California occur in one of the most urbanized and fragmented landscapes on the planet and have lost up to 80% of their native habitat. Orange County is one of the last strongholds for this pond-breeding amphibian in the region, and ongoing restoration efforts targeting S. hammondii have involved habitat protection and the construction of artificial breeding ponds. These efforts have successfully increased breeding activity, but genetic characterization of the populations, including estimates of effective population size and admixture between the gene pools of constructed artificial and natural ponds, has never been undertaken. Using thousands of genome-wide single-nucleotide polymorphisms, we characterized the population structure, genetic diversity, and genetic connectivity of spadefoots in Orange County to guide ongoing and future management efforts. We identified at least 2, and possibly 3 major genetic clusters, with additional substructure within clusters indicating that individual ponds are often genetically distinct. Estimates of landscape resistance suggest that ponds on either side of the Los Angeles Basin were likely interconnected historically, but intense urban development has rendered them essentially isolated, and the resulting risk of interruption to natural metapopulation dynamics appears to be high. Resistance surfaces show that the existing artificial ponds were well-placed and connected to natural populations by low-resistance corridors. Toad samples from all ponds (natural and artificial) returned extremely low estimates of effective population size, possibly due to a bottleneck caused by a recent multi-year drought. Management efforts should focus on maintaining gene flow among natural and artificial ponds by both assisted migration and construction of new ponds to bolster the existing pond network in the region.

Improving Quality in the Treatment of Pediatric Forearm Fractures: Minimizing the Need for Repeat Intervention With Long-arm Extension Casting.

PURPOSE: Repeat intervention for pediatric forearm fractures after closed manipulation is as high as 46% with flexed elbow (FE) long-arm casts. Casting with the elbow extended (EE) has been advocated as an alternative technique. We documented outcomes of patients treated with closed manipulation and casting with EE long-arm casts for displaced, diaphyseal both-bone forearm fractures. METHODS: We retrospectively reviewed charts for patients who had sedated manipulations and casting for closed, diaphyseal forearm fractures. Open fractures, immediate surgical intervention, metabolic bone disease, recurrent fractures, and Monteggia injuries were excluded. Closed manipulations were performed by orthopaedic residents assisted by cast technicians, with sedation provided by emergency department physicians. Radiographic angulation and displacement of the radius and ulna on immediate postreduction radiographs and all follow-up radiographs were recorded. Patients requiring repeat intervention were compared with those who did not by using the Mann-Whitney U and Fisher exact tests. RESULTS: Of 86 patients (7.2±2.8 y) available for analysis, 82 (95.3%) completed treatment after a single-sedated manipulation and placement of an EE long-arm cast. There were no malunions or nonunions. The average follow-up was 50 days. Four (4.7%) patients required repeat interventions (2 had surgery, 1 had a repeat sedated manipulation, and 1 had a nonsedated manipulation). There were no statistically significant differences in age, sex, laterality, fracture position in the diaphysis, or immediate postreduction angulation of the radius or ulna. A literature review showed average repeat intervention rates of 14.9% (range, 0% to 45.9%) for FE casts and 3.3% (range, 0% to 15%) for EE casts. CONCLUSIONS: There was a low rate of repeat interventions (4.7%) in patients with EE casts compared with historical rates for FE casts. Improving the quality of health care involves identifying and implementing practices that provide the best outcomes at the lowest costs. The use of EE long-arm casts following closed manipulation of pediatric forearm fractures may decrease the rate of repeat manipulation or surgery compared with conventional FE casts. LEVEL OF EVIDENCE: Level IV-case series.

Atlantoaxial rotatory subluxation in children.

Atlantoaxial rotatory subluxation is a rare condition in which patients present with the acute onset of torticollis. Atlantoaxial rotatory subluxation represents a spectrum of disease from muscle spasm to a fixed mechanical block to reduction of the atlantoaxial complex. If left untreated, some cases may resolve spontaneously; however, other cases may result in the development of secondary changes in the bony anatomy of the atlantoaxial joint, leading to persistent deformity. Diagnosis of the condition is largely clinical but can be aided by various imaging modalities, including radiographs, dynamic CT scanning, three-dimensional CT reconstructions, or MRI. Consideration should always be given to infection or other inflammatory disease as an underlying, precipitating cause. Treatments include observation, the use a cervical collar and analgesics, halter or skeletal traction, and posterior fusion of C1-C2. The most important factor for success of conservative treatment is the time from the onset of symptoms to recognition and the initiation of treatment.

Epiphyseal-entry cannulated screws for temporary guided growth of the knees: a retrospective review of 89 cases.

Guided growth affects the physis in children to produce a desired effect. Several devices achieve alteration of growth, including staples, plates, and screws. Complications can include device failures, failure to modulate growth as expected, and unintended physeal arrest. We present the results of a unique technique designed to minimize these complications. This was a retrospective review of guided growth at the knee at a single institution utilizing cannulated screws with epiphyseal-entry points. Each case was reviewed to determine the presence of complications related to guided growth, including implant breakage, implant pull-out or pull-through, iatrogenic physeal arrest, failure to modulate growth, and the incidence of revision surgeries. There were 89 patients who had 146 epiphyseal-entry guided growth procedures with a total of 221 4.5 mm cannulated screws. There were no iatrogenic physeal arrests. Five (2.26%) screws in 4 (4.49%) patients had either a broken screw or screw pull-out/pull-through requiring revision procedures. Three patients had osteotomies after skeletal maturity. Four had revision-guided growth for other reasons: 2 due to a lack of timely follow-up, 1 for iatrogenic genu varum without implant failure, and 1 due to recurrent deformity after implant removal. Revision procedures were unanticipated in 6 (6.74%) patients. This study describes a technique for placing cannulated screws at the knee with epiphyseal starting points. Our rate of complications and number of revision surgeries compare favorably with those noted for other techniques. Guided growth using epiphyseal-entry cannulated screws is a safe, effective option for most patients.

Accuracy of screw placement during vertebral body tethering using fluoroscopic guidance and anatomic landmarks.

PURPOSE: To determine the accuracy of screw placement using fluoroscopy and anatomic landmarks during vertebral body tethering (VBT) surgery. METHODS: Ten patients with 73 VBT screws were converted to posterior spinal fusion (PSF) after continued curve progression. The positions of each VBT screw were analyzed using intraoperative computed tomography (CT) scans performed for image guidance during VBT. Differences for screws placed using an open versus thoracoscopic approach were noted for the screw position in each vertebra, distance from the spinal canal, unicortical versus bicortical placement, the distance of screw tips from the thoracic aorta, and impingement of screws on adjacent rib heads. RESULTS: Seventy three (73) screws in ten (10) patients were available for analysis. Only 21% of screws were placed traversing the middle one-third of the vertebral body, without spinal canal penetration, with the distal tip placed unicortically or bicortically as planned, and without touching the thoracic aorta. The rates of non-ideal screw placement were not significantly different for screws placed via thoracoscopic versus open approaches. Five (5) screws (6.8%) penetrated the spinal canal 1-2 mm, but without known clinical sequelae. CONCLUSION: The majority of VBT screws available for analysis were placed in non-ideal positions, suggesting that accurate screw placement using intraoperative fluoroscopy and anatomic landmarks can be challenging, but without adverse clinical consequences.

Improving prediction of progression of idiopathic scoliosis based on curve size and skeletal maturity.

PURPOSE: To define the risk of curve progression of idiopathic scoliosis (IS) to 35°, 40°, 45°, and 50° based on current curve magnitude and Sanders stage for boys and girls, using a large cohort of patients and encounters, to improve granularity and allow more accurate estimations to guide treatment. METHODS: Retrospective analysis of a prospectively collected scoliosis database. Generalized estimation equation logistic regression models estimated probabilities of curve progression to 35°, 40°, 45°, and 50° based on starting curve size and Sanders stage. Probabilities and their 95% confidence intervals were calculated for each combination of variables to each endpoint separately for boys and girls. RESULTS: A total of 309 patients (80% girls) were included. Starting curve size and Sanders stage were significant predictors for progression in both sexes (all P ≤ 0.04). Higher starting curve sizes and lower Sanders stages were associated with greater odds of progression. Risk of progression was still present even at higher Sanders stages. CONCLUSION: IS curves follow a predictable pattern, having more risk for progression when curves are larger and Sanders stages are smaller. Risk of curve progression is a spectrum based on these factors, indicating some risk of progression exists even for many smaller curves with higher Sanders stages. The improved granularity of this analysis compared to prior efforts may be useful for counseling patients about the risks of curve progression to various curve size endpoints and may aid shared decision-making regarding treatments. LEVEL OF EVIDENCE OR CLINICAL RELEVANCE: Level III: retrospective cohort study.