The effectiveness of a protocol without routine radiographs for follow-up of adolescent idiopathic scoliosis patients (CURVE): a study protocol.

BACKGROUND AND PURPOSE: Current follow-up protocols for adolescent idiopathic scoliosis (AIS) are based on consensus and consist of regular full-spine radiographs to monitor curve progression and surgical complications. Consensus exists to avoid inappropriate use of radiographs in children. It is unknown whether a standard radiologic follow-up (S-FU) approach is necessary or if a patient-empowered follow-up (PE-FU) approach can reduce the number of radiographs without treatment consequences. METHODS AND ANALYSES: A nationwide multicenter pragmatic randomized preference trial was designed for 3 follow-up subgroups (pre-treatment, post-brace, post-surgery) to compare PE-FU and S-FU. 812 patients with AIS (age 10-18 years) will be included in the randomized trial or preference cohorts. Primary outcome is the proportion of radiographs with a treatment consequence for each subgroup. Secondary outcomes consist of the proportion of patients with delayed initiation of treatment due to non-routine radiographic follow-up, radiation exposure, societal costs, positive predictive value, and interrelation of clinical assessment, quality of life, and parameters for initiation of treatment during follow-up. Outcomes will be analyzed using linear mixed-effects models, adjusted for relevant baseline covariates, and are based on intention-to-treat principle. Study summary: (i) a national, multicenter pragmatic randomized trial addressing the optimal frequency of radiographic follow-up in patients with AIS; (ii) first study that includes patient-empowered follow-up; (iii) an inclusive study with 3 follow-up subgroups and few exclusion criteria representative for clinical reality; (iv) preference cohorts alongside to amplify generalizability; (v) first study conducting an economic evaluation comparing both follow-up approaches.

The Dutch version of the Spinal Appearance Questionnaire for adolescents with idiopathic scoliosis: patient-based cross-cultural adaptation and measurement properties evaluation.

PURPOSE: Adolescent idiopathic scoliosis (AIS) affects the appearance of spine and trunk. The Spinal Appearance Questionnaire (SAQ) assesses the perception of appearance in AIS patients. The aim of this study is to translate and culturally adapt the recommended short version of the SAQ into Dutch and to test its measurement properties. METHODS: A Dutch SAQ (14-item; appearance and expectations domains) was developed following guidelines for translation and cross-cultural adaptation. The COSMIN Study Design checklist was used for measurement properties evaluation. In this multicenter study, the Dutch SAQ, SRS-22R and NPRS (back pain) were administered to 113 AIS patients (aged 15.4 years [SD 2.2], 21.2% male). Floor and ceiling effects were evaluated for content analysis. For reliability, internal consistency (Cronbach's alpha) and test-retest reliability (ICC; n = 34) were evaluated. Predefined hypotheses of relationships with other questionnaires and between subgroups based on scoliosis severity (radiological and clinical) were tested for construct validity. Exploratory factor analysis (EFA) was performed to investigate the validity of the underlying structure of this 14-item questionnaire. RESULTS: No floor and ceiling effects were found for domains and total scores. Cronbach's alpha ranged from 0.84 to 0.89. ICCs varied from 0.76 to 0.77. For construct validity, 89% (8/9) of the predefined hypotheses were confirmed. Significant higher scores for the appearance domain were found for subgroups based on radiological (Cobb angle; > 25.0°) and clinical outcomes. (Angle of Trunk Rotation; > 9.0°). A two-factor structure was found (EV 5.13; 36.63% explained variance). CONCLUSION: The Dutch SAQ is an adequate, valid and reliable instrument to evaluate patients' perception of appearance in AIS. LEVEL OF EVIDENCE: Level I-diagnostic studies.

Incomplete spinal cord injury following minor trauma in two siblings with spondylocostal dysostis type 6.

Biallelic pathogenic variants of the RIPPLY2 gene have been recognized to cause a subtype of autosomal recessive spondylocostal dysostosis (SCDO6), characterized by predominant cervical spine malformation with minor or absent involvement of the ribs. To date, RIPPLY2 associated SCDO6 has been described in ten patients in five studies with accompanying clinical symptoms varying from transient and recurrent torticollis to flaccid quadriplegia. Here, we describe two additional patients in one family in which the c.A238T:p.Arg80* RIPPLY2 mutation in the homozygous state, was associated with severe malformation of the posterior elements of the cervical vertebral column. In both cases neurological symptoms occurred early in life due to spinal cord compromise. These two cases, in keeping with previous reports, highlight the early and progressive natural history of cervical deformity in this rare skeletal dysplasia and the need for close neurological and radiological surveillance. Surgical decision-making needs to carefully balance the need for early intervention to protect spinal cord function on one hand, with the problem of bone malformation and skeletal immaturity on the other.

Validity and reliability of the adapted Dutch version of the Brace Questionnaire (BrQ).

BACKGROUND AND PURPOSE: The Brace Questionnaire (BrQ) is a disease-specific health-related quality of life (HRQOL) instrument for measuring perceived health status of scoliosis patients undergoing brace treatment. The purpose of this study is to evaluate the validity and reliability of a translated and culturally adapted Dutch version of the BrQ. PATIENTS AND METHODS: The original Greek BrQ was translated into Dutch and a cross-cultural adaptation and validation processes were conducted. Subsequently, 80 adolescent idiopathic scoliosis (AIS) patients undergoing active brace treatment were included from 4 scoliosis centers to evaluate the validity and reliability of the Dutch version of the BrQ. The questionnaire's floor and ceiling effects, internal consistency, and test-retest reliability were assessed. Concurrent validity was evaluated by comparing the BrQ with the revised Scoliosis Research Society 22-item questionnaire (SRS-22r) scores. RESULTS: The mean total BrQ score was 75.9 (standard deviation [SD] 11.3) and the mean domain scores varied between 3.4 (SD 0.9) and 4.2 (SD 0.7) for the domains "vitality" and "bodily pain," respectively. There were no floor and ceiling effects for the total BrQ score. The BrQ showed satisfactory internal consistency in most subdomains with a Cronbach's α ranging between 0.35 for the domain "general health perception" and 0.89 for the domain "self-esteem and aesthetics." Excellent test-retest reproducibility was observed for the total BrQ score (ICC 0.91), and the BrQ was successfully validated against the SRS-22r. CONCLUSION: The translated and culturally adapted Dutch version of the BrQ is a valid and reliable HRQOL instrument for AIS patients undergoing brace treatment.

Translation and validation of the Dutch Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) to evaluate health-related quality of life in patients with symptomatic spinal metastases.

BACKGROUND: The primary goal of palliative treatment of spinal metastases is to maintain or improve health-related quality of life (HRQOL). We translated and validated a Dutch version of The Spine Oncology Study Group Outcome Questionnaire (SOSGOQ2.0), a valid and reliable 20-item questionnaire to evaluate HRQOL in patients with spinal metastases. METHODS: After cross-cultural translation and adaptation, the questionnaire was pre-tested in fifteen patients referred for spine surgery and/or radiotherapy. This resulted in a final questionnaire that was sent to patients for assessment of internal consistency, construct (i.e., convergent and divergent) validity, discriminative power and test-retest reliability. RESULTS: Overall, 147 patients (mean age 65.6 years, SD = 10.4) completed the questionnaire after a median time of 45.4 months (IQR = 18.9-72.9) after spine surgery and/or radiotherapy. Internal consistency was good for the Physical function, Pain, and Mental health domains (α = 0.87, 0.86, 0.72), but not for Social function (α = 0.04). Good convergent validity was demonstrated except for Social function (rs = 0.37 95%CI = 0.21-0.51). Discriminative power between patients with ECOG performance scores of 0-1 and 2-4 was found on all domains and Neurological function items. Test-retest reliability was acceptable for Physical function, Pain and Mental health (ICC = 0.89 95%CI = 0.81-0.94, ICC = 0.88 95%CI = 0.78-0.93, ICC = 0.68 95%CI = 0.48-0.81), whereas ICC = 0.45 (95%CI = 0.17-0.66) for Social function was below threshold. After removing item 20 from the Social function domain, internal consistency improved, and convergent validity and test-retest reliability were good. CONCLUSION: The Dutch version of the SOSGOQ2.0 questionnaire is a reliable and valid tool to measure HRQOL in patients with spinal metastases. Item 20 was removed to retain psychometric properties.

Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study.

CONTEXT: Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity. OBJECTIVE: To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS. METHODS: We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature. RESULTS: We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below -2.5) and 143 (54%) had osteopenia (T-score -1 to -2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P = .005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified. CONCLUSION: Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients.

Rate and Predictors of Failure in the Conservative Management of Stable Thoracolumbar Burst Fractures: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review. OBJECTIVES: Management of stable traumatic thoracolumbar burst fractures in neurologically-intact patients remains controversial. Conservative management fails in a subset of patients who require subsequent surgical fixation. The aim of this review is to (1) determine the rate of conservative management failure, and (2) analyze predictive factors at admission influencing conservative management failure. METHODS: A systematic review adhering to PRISMA guidelines was performed. Studies with data pertaining to traumatic thoracolumbar burst fractures without posterior osteoligamentous injury (e.g. AO Type A3/A4) and/or the rate and predictive factors of conservative management failure were included. Risk of bias appraisal was performed. Pooled analysis of rates of failure was performed with qualitative analysis of predictors of conservative management failure. RESULTS: 16 articles were included in this review (11 pertaining to rate of conservative management failure, 5 pertaining to predictive risk factors). Rate of failure of conservative management from a pooled analysis of 601 patients is 9.2% (95% CI: 4.5%-13.9%). Admission factors predictive of conservative management failure include age, greater initial kyphotic angle, greater initial interpedicular distance, smaller initial residual canal size, greater Load Sharing Classification (LSC) score and greater admission Visual Analog Scale (VAS) pain scores. CONCLUSION: A proportion (9.2%) of conservatively managed, neurologically-intact thoracolumbar burst fractures fail conservative management. Among other factors, age, kyphotic angle, residual canal area and interpedicular distance should be investigated in prospective studies to identify the subset of patients prone to failure of conservative management. Surgical management should be carefully considered in patients with the above risk factors.

Effects of 8 years of growth hormone treatment on scoliosis in children with Prader-Willi syndrome.

OBJECTIVE: Scoliosis is frequently seen in children with Prader-Willi syndrome (PWS). There is still concern that growth hormone (GH) treatment might increase the risk of onset or progression of scoliosis. Short-term data suggested no adverse effects of GH on scoliosis, but long-term effects of GH treatment on development of scoliosis in PWS are unknown. This study investigated the effects of 8 years of GH treatment on scoliosis in children with PWS. DESIGN: Open-label, prospective cohort study in 103 children with PWS receiving GH for 8 years was analyzed. Prevalence and severity of scoliosis were compared to a group of 23 age-matched GH-untreated children with PWS. METHODS: Spine X-rays and DEXA-scans were performed, and Cobb angel was measured by two independent observers. RESULTS: After 8 years of GH treatment, at median age of 10.8 years, prevalence of scoliosis was 77.7%. No difference in prevalence or severity of scoliosis was found between GH-treated and age-matched untreated children with PWS (P = 0.409 and P = 0.709, respectively). Height SDS and trunkLBM were significantly higher in GH-treated children. Higher bone mineral density of the lumbar spine was found in children without scoliosis after 8 years of GH. Bone mineral apparent density of lumbar spine (BMADLS) SDS was associated with lower Cobb angle (r = -0.270, P = 0.008). CONCLUSIONS: Eight years of GH treatment has no adverse effects on the prevalence and severity of scoliosis in children with PWS until 11 years of age. As BMADLS SDS is inversely associated with Cobb angle, it is pivotal to optimize the BMD status in children with PWS.

The Role of Spinal Orthoses in Osteoporotic Vertebral Fractures of the Elderly Population (Age 60 Years or Older): Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: Spinal orthoses have been generally used in the management of osteoporotic vertebral fractures in the elderly population with purported positive biomechanical and functional effects. To our knowledge, this is the first systematic review of the literature examining the role of spinal orthoses in osteoporotic elderly patients who sustain low energy trauma vertebral fractures. METHODS: A systematic literature review adherent to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Methodical searches utilizing MEDLINE, EMBASE, Google Scholar, and Cochrane Databases was performed. RESULTS: Of the 2019 articles initially retrieved, 7 published articles (4 randomized controlled trials and 3 prospective cohort studies) satisfied the inclusion criteria. Five studies reported improvement in quantitative measurements of spinal column stability when either a rigid or semirigid orthosis was used, while 1 study was equivocal. The studies also showed the translation of biomechanical benefit into significant functional improvement as manifested by improved postural stability and reduced body sway. Subjective improvement in pain scores and quality of life was also noted with bracing. CONCLUSION: The use of spinal orthoses in neurologically intact elderly patients aged 60 years and older with osteoporotic compression vertebral fractures results in improved biomechanical vertebral stability, reduced kyphotic deformity, enhanced postural stability, greater muscular strength and superior functional outcomes.

The Safety Profile of Intentional or Iatrogenic Sacrifice of the Artery of Adamkiewciz and Its Vicinity's Spinal Segmental Arteries: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: There is paucity of consensus on whether (1) the artery of Adamkiewicz (AoA) and (2) the number of contiguous segmental spinal arteries (SSAs) that can be safely ligated without causing spinal cord ischemia. The objective of this review is to determine the risk of motor neurological deficits from iatrogenic sacrifice of the (1) AoA and (2) its vicinity's SSAs. METHODS: Systematic review of the spine and vascular surgery was carried out in accordance to PRISMA guidelines. Outcomes in terms of risk of postoperative motor neurological deficit with occlusion of the AoA, bilateral contiguous SSAs, or unilateral contiguous SSAs were analyzed. RESULTS: Ten articles, all retrospective case series, were included. Three studies (total N = 50) demonstrated a postoperative neurological deficit risk of 4.0% when the AoA is occluded. When 1 to 6 pairs of SSAs (without knowledge of AoA location) were ligated, the postoperative neurological deficit risk was 0.6%, as compared with 5.4% when more than 6 bilateral pairs of SSAs were ligated (relative risk [RR] = 0.105, 95% CI 0.013-0.841, P = .0337). For unilateral ligation of SSAs of two to nine levels, the risk of postoperative neurological deficit does not exceed 1.3%. CONCLUSION: The current best evidence indicates that (1) occlusion of the AoA and (2) occlusion of up to 6 pairs of SSAs is associated with a low risk of postoperative neurological deficit. This limited number of low quality studies restrict the ability to draw definitive conclusions. Ligation of AoA and SSAs should only be undertaken when absolutely required to mitigate the small but devastating risk of paralysis.

Cyanoacrylate Dermal Closure in Spine Surgery: Systematic Review and Pooled Analysis.

STUDY DESIGN: Systematic review. OBJECTIVES: Cyanoacrylate glue closure has been utilized for dermal closure in surgical incisions. Its safety and efficacy in spine surgery are not established. The authors perform a systematic review to determine the rate of surgical site infection (SSI), wound dehiscence, and wound erythema with cyanoacrylate dermal closure in spine surgery. METHODS: A systematic review adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed utilizing the PubMed/MEDLINE, EMBASE, and Cochrane databases on patients undergoing spine surgery with cyanoacrylate dermal closure. Pooled analysis was performed with stratification of patients according to spinal level and the presence/absence of instrumentation. Risk-of-bias and methodological quality was appraised using 17 prespecified criteria. RESULTS: Five articles (1 retrospective cohort study, 4 cases series) with a total of 1282 patients were included. A total of 967 patients, all diagnosed with degenerative spine disease, were suitable for pooled analysis. In 290 patients who underwent anterior cervical discectomy and fusion, and in 23 patients with posterior cervical decompression (without instrumentation), there was 0% rate of SSI, wound dehiscence, and erythema. In 489 patients who underwent lumbar microdiscectomy, there was 0.41% rate of SSI, 0.20% rate of wound dehiscence, and 0.20% rate of wound erythema. In 165 lumbar laminectomy patients, there was a 1.82% rate of SSI, 0.61% rate of wound dehiscence, and 0% rate of wound erythema. CONCLUSION: Cyanoacrylate dermal closure for the aforementioned procedures is associated with low rates of wound complications (SSI, dehiscence, and erythema). Further studies should be performed, especially in nondegenerative surgery, instrumented thoracic and lumbar spine surgery.

Does Combined Anterior-Posterior Approach Improve Outcomes Compared with Posterioronly Approach in Traumatic Thoracolumbar Burst Fractures?: A Systematic Review.

The aim of this systematic review was to evaluate the surgical, radiological, and functional outcomes of posterior-only versus combined anterior-posterior approaches in patients with traumatic thoracolumbar burst fractures. The ideal approach (anterior-only, posterior-only, or combined anterior-posterior) for the surgical management of thoracolumbar burst fracture remains controversial, with each approach having its advantages and disadvantages. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed (registration no., CRD42018115120). The authors reviewed comparative studies evaluating posterior-only approach compared with combined anterior-posterior approaches with respect to clinical, surgical, radiographic, and functional outcome measures. Five retrospective cohort studies were included. Postoperative neurological deterioration was not reported in either group. Operative time, estimated blood loss, and postoperative length of stay were increased among patients in the combined anterior-posterior group in one study and equivalent between groups in another study. No significant difference was observed between the two approaches with regards to long-term postoperative Cobb angle (mean difference, -0.2; 95% confidence interval, -5.2 to 4.8; p =0.936). Moreover, no significant difference in functional patient outcomes was observed in the 36item Short-Form Health Survey, Visual Analog Scale, and return-to-work rates between the two groups. The available evidence does not indicate improved clinical, radiologic (including kyphotic deformity), and functional outcomes in the combined anterior-posterior and posterior-only approaches in the management of traumatic thoracolumbar burst fractures. Further studies are required to ascertain if a subset of patients will benefit from a combined anterior-posterior approach.

Prophylactic postoperative measures to minimize surgical site infections in spine surgery: systematic review and evidence summary.

BACKGROUND CONTEXT: There are three phases in prophylaxis of surgical site infections (SSI): preoperative, intraoperative and postoperative. There is lack of consensus and paucity of evidence with SSI prophylaxis in the postoperative period. PURPOSE: To systematically evaluate the literature, and provide evidence-based summaries on postoperative measures for SSI prophylaxis in spine surgery. STUDY DESIGN: Systematic review, meta-analysis, evidence synthesis. METHODS: A systematic review conforming to PRIMSA guidelines was performed utilizing PubMed (MEDLINE), EMBASE, and the Cochrane Database from inception to January 2019. The GRADE approach was used for quality appraisal and synthesis of evidence. Six postoperative care domains with associated key questions were identified. Included studies were extracted into evidence tables, data synthesized quantitatively and qualitatively, and evidence appraised per GRADE approach. RESULTS: Forty-one studies (nine RCT, 32 cohort studies) were included. In the setting of preincisional antimicrobial prophylaxis (AMP) administration, use of postoperative AMP for SSI reduction has not been found to reduce rate of SSI in lumbosacral spine surgery. Prolonged administration of AMP for more than 48 hours postoperatively does not seem to reduce the rate of SSI in decompression-only or lumbar spine fusion surgery. Utilization of wound drainage systems in lumbosacral spine and adolescent idiopathic scoliosis corrective surgery does not seem to alter the overall rate of SSI in spine surgery. Concomitant administration of AMP in the presence of a wound drain does not seem to reduce the overall rate of SSI, deep SSI, or superficial SSI in thoracolumbar fusion performed for degenerative and deformity spine pathologies, and in adolescent idiopathic scoliosis corrective surgery. Enhanced-recovery after surgery clinical pathways and infection-specific protocols do not seem to reduce rate of SSI in spine surgery. Insufficient evidence exists for other types of spine surgery not mentioned above, and also for non-AMP pharmacological measures, dressing type and duration, suture and staple management, and postoperative nutrition for SSI prophylaxis in spine surgery. CONCLUSIONS: Despite the postoperative period being key in SSI prophylaxis, the literature is sparse and without consensus on optimum postoperative care for SSI prevention in spine surgery. The current best evidence is presented with its limitations. High quality studies addressing high risk cohorts such as the elderly, obese, and diabetic populations, and for traumatic and oncological indications are urgently required.

Anterior versus posterior approach in traumatic thoracolumbar burst fractures deemed for surgical management: Systematic review and meta-analysis.

Uncertainties remain regarding the optimal surgical approach in the treatment of traumatic thoracolumbar burst fractures. We aim to compare the surgical, radiological and functional outcomes in anterior versus posterior approaches in patients with traumatic thoracolumbar burst fractures deemed for surgical management. A systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Qualitative analysis and where suitable, meta-analysis were performed to compute pooled estimates of the differences between anterior and posterior approaches. A total of six studies (three observational, one prospective non-randomized trial, two randomized controlled trials) were included. There were no cases of postoperative neurological decline. Meta-analysis demonstrates a longer duration (Mean Difference (MD) + 81.68, 95% CI 39.20 to 123.16, p < 0.001) and increased estimated blood loss (MD + 426.27, 95% CI 119.84 to 732.70, p = 0.006) for the anterior approach. No difference between approaches was found regarding length of hospital stay, late postoperative kyphotic angle, construct failure rate, instrumentation revision rate, rate of return to work, and total hospital charges. Limitations include the small number of, and heterogeneity across studies. Given the similarities in neurological, radiological and functional outcomes between the two approaches, the longer duration and estimated blood loss in the anterior approach should be a point of consideration when selecting the surgical approach. There is an urgent need for contemporary, high quality research in this area.

Factors predictive of topographical accuracy in spine level localization.

BACKGROUND: Pre-operative spine level localization by palpation of anatomical landmarks (ribs, spinous processes) in posterior approaches for surgeries from T4 to L2 is often inaccurate. This can lead to ineffective utilization of procedural time, increased radiation dose, potentially longer skin incision and wrong level surgery. Factors affecting topographical accuracy includes body mass index (BMI) of the patient, congenital or acquired deformity and knowledge of topographical anatomy. METHODS: All patients had the presumed location of their pathology marked on the skin using anatomical landmarks prior to application of the Target Tape® (Vancouver, BC, Canada) and verification using an anterior-posterior radiograph. Potential factors predictive of accurate pre-operative spine level localization such as age, gender, BMI, palpable deformity, pathology related interspinous distance (ISPD) and pathology related skin to spinous process distance were evaluated. RESULTS: A prospective study was performed with 30 consecutive patients undergoing posterior spine surgery (T4 to L2). Accuracy of pathology related spine level localization using anatomical landmarks was only 40%. Pathology related ISPDs of more than 10 mm and palpable deformity was significantly correlated with successful determination of spine levels using anatomical landmarks. CONCLUSIONS: This study showed that poor spine level localization using anatomical landmarks was associated with pathology related ISPDs of less than 10 mm. Conversely, patients with palpable spinal deformity have their levels easily localized.

A prospective serial MRI study following acute traumatic cervical spinal cord injury.

PURPOSE: In acute traumatic cervical spinal cord injury (SCI) patients, we sought to characterize how objective MRI measures of injury change during the first 3 week post-injury. METHODS: Six MRI scans each were planned in 19 cervical SCI patients within the first 3 week post-injury. Length of cord edema, maximum spinal cord compression, maximum canal compromise, and presence and length of hematoma were measured. RESULTS: Length of spinal cord edema increased in the first 48 h after SCI, followed by a gradual decrease in the 3 weeks after injury. This was predominantly seen in the more severe grades of SCI. Hematoma in the spinal cord was seen in all AIS-A and B patients. CONCLUSION: This study demonstrates the dynamic nature of imaging changes on MRI in the first weeks after injury and highlights the importance of taking into account the timing of imaging when interpreting objective measures of damage.

Histological characteristics of diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a predominantly radiographic diagnosis and histological knowledge of DISH is limited. The aim of this study was to describe the histological characteristics of DISH in the spinal column and to study the relation between DISH and intervertebral disc (IVD) degeneration. Therefore, 10 human cadaveric spines with fluoroscopic evidence of DISH were compared with 10 controls. Plain radiographs and computed tomography (CT) scans were obtained and tissue blocks were resected from three predefined levels of all specimens. The microscopic sections were scored by two blinded observers using a newly developed scoring system specific for characteristics of DISH and a validated scoring system for IVD degeneration. Maximum IVD height was measured on the CT scans. Analyses were performed using Fisher's exact test and Student's t-test. When compared to controls, the right sided sections from DISH specimens showed partial or complete bone bridges, consisting of cortical woven bone, accompanied by morphological changes in the adjoining part of the IVD. Using the histological scoring system for DISH, all parameters were significantly different between the DISH and control group (p < 0.01). The contralateral location did not show differences between the groups. The overall degree of IVD degeneration and height of IVD was comparable for the two groups. The histopathological changes observed in spines with DISH corresponded to the fluoroscopic images and CT scans. The degree of IVD degeneration and IVD height was comparable for both groups, suggesting a limited role for IVD degeneration in the pathogenesis of DISH. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:140-146, 2017.

The dog as an animal model for intervertebral disc degeneration?

STUDY DESIGN: Prospective observational and analytic study. OBJECTIVE: To investigate whether spontaneous intervertebral disc degeneration (IVDD) occurring in both chondrodystrophic (CD) and nonchondrodystrophic dogs (NCD) can be used as a valid translational model for human IVDD research. SUMMARY OF BACKGROUND DATA: Different animal models are used in IVDD research, but in most of these models IVDD is induced manually or chemically rather than occurring spontaneously. METHODS: A total of 184 intervertebral discs (IVDs) from 19 dogs of different breeds were used. The extent of IVDD was evaluated by macroscopic grading, histopathology, glycosaminoglycan content, and matrix metalloproteinase 2 activity. Canine data were compared with human IVD data acquired in this study or from the literature. RESULTS: Gross pathology of IVDD in both dog types (CD and NCD) and humans showed many similarities, but the cartilaginous endplates were significantly thicker and the subchondral cortices significantly thinner in humans than in dogs. Notochordal cells were still present in the IVDs of adult NCD but were not seen in the CD breeds or in humans. Signs of degeneration were seen in young dogs of CD breeds (<1 year of age), whereas this was only seen in older dogs of NCD breeds (5-7 years of age). The relative glycosaminoglycan content and metalloproteinase 2 activity in canine IVDD were similar to those in humans: metalloproteinase 2 activity increased and glycosaminoglycan content decreased with increasing severity of IVDD. CONCLUSION: IVDD is similar in humans and dogs. Both CD and NCD breeds may therefore serve as models of spontaneous IVDD for human research. However, as with all animal models, it is important to recognize interspecies differences and, indeed, the intraspecies differences between CD and NCD breeds (early vs. late onset of IVDD, respectively) to develop an optimal canine model of human IVDD.

Identification of cell surface-specific markers to target human nucleus pulposus cells: expression of carbonic anhydrase XII varies with age and degeneration.

OBJECTIVE: Back pain is a major cause of disability, affecting millions of people worldwide. One cause of axial back pain is degeneration of the nucleus pulposus (NP) of the intervertebral disc. This study was undertaken to investigate associations of NP cells with cell surface-specific proteins that differ from proteins in closely related cell types, i.e., intervertebral disc anulus fibrosus (AF) cells and articular cartilage (AC) chondrocytes, in order to identify potential surface molecules for directed delivery of therapeutic agents. METHODS: We conducted a complementary DNA microarray analysis of 16 human samples from 6 donors, followed by gene list reduction using a systematic approach. Genes that were more highly expressed in NP than AC cells, contained transmembrane domains, and appeared attractive for targeting were assessed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). As a viable candidate, carbonic anhydrase XII (CAXII) was analyzed at the protein level by immunohistochemistry and functional study. RESULTS: Microarray results demonstrated a clear divide between the AC and AF and between the AC and NP samples. However, the transcriptomic profile of AF and NP samples displayed a greater intersubject similarity. Of the 552 genes with up-regulated expression in NP cells, 90 contained transmembrane domains, and 28 were quantified by RT-PCR. Most intense CAXII labeling was observed in the NP of discs from young subjects and in degenerative tissue. CONCLUSION: CAXII may be considered for detection or targeting of degenerating disc cells. Furthermore, CAXII may be involved in pH regulation of NP cells. Its potential for directed delivery of regenerative factors and its functional role in NP cell homeostasis warrant further investigation.