Reconstituting human somitogenesis in vitro.

The segmented body plan of vertebrates is established during somitogenesis, a well-studied process in model organisms; however, the details of this process in humans remain largely unknown owing to ethical and technical limitations. Despite recent advances with pluripotent stem cell-based approaches1-5, models that robustly recapitulate human somitogenesis in both space and time remain scarce. Here we introduce a pluripotent stem cell-derived mesoderm-based 3D model of human segmentation and somitogenesis-which we termed 'axioloid'-that captures accurately the oscillatory dynamics of the segmentation clock and the morphological and molecular characteristics of sequential somite formation in vitro. Axioloids show proper rostrocaudal patterning of forming segments and robust anterior-posterior FGF-WNT signalling gradients and retinoic acid signalling components. We identify an unexpected critical role of retinoic acid signalling in the stabilization of forming segments, indicating distinct, but also synergistic effects of retinoic acid and extracellular matrix on the formation and epithelialization of somites. Comparative analysis demonstrates marked similarities of axioloids to the human embryo, further validated by the presence of a Hox code in axioloids. Finally, we demonstrate the utility of axioloids for studying the pathogenesis of human congenital spine diseases using induced pluripotent stem cells with mutations in HES7 and MESP2. Our results indicate that axioloids represent a promising platform for the study of axial development and disease in humans.

Safety and clinical contribution of computed tomography-guided biopsy for cervical spine lesion.

INTRODUCTION: The purpose is to clarify the safety and clinical contribution of computed tomography (CT)-guided percutaneous needle-biopsy for patients with cervical spine lesion. MATERIAL AND METHODS: Between June 2015 and August 2022, CT-guided percutaneous needle biopsies were performed for 15 cervical spine lesions of 15 patients (8 male, 7 female; 2-81 years old). The technical success, clinical contribution, and safety were evaluated. Technical success was defined as the completion of the biopsy procedure. Clinical contribution was defined as any contribution to the therapeutic strategy. Safety was assessed by the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: The technical success rate was 100%. In all 15 patients, nontarget organs (e.g., major vessels, spinal cord) could be avoided. The post-biopsy histological diagnoses were myeloma (n = 2), metastatic adenocarcinoma (n = 2), chordoma (n = 2), Langerhans cell histiocytosis (n = 3), and one case each of malignant lymphoma, schwannoma, pyogenic spondylitis, non-pyogenic spondylitis, degenerative change, and non-pathological fracture. All of these diagnoses contributed to the therapeutic strategy decisions. One case of grade 2 pain was observed, but no complications with grade 3 or more were observed during or after the biopsies. CONCLUSION: CT-guided percutaneous needle biopsies for cervical spine lesions were safe and clinically beneficial.

What does degeneration at the cervicothoracic junction tell us? A kinematic MRI study of 93 individuals.

PURPOSE: Current decision-making in multilevel cervical fusion weighs the potential to protect adjacent levels and reduce reoperation risk by crossing the cervicothoracic junction (C7/T1) against increased operative time and risk of complication. Careful planning is required, and the planned distal and adjacent levels should be assessed for degenerative disc disease (DDD). This study assessed whether DDD at the cervicothoracic junction was associated with DDD, disc height, translational motion, or angular variation in the adjacent superior (C6/C7) or inferior (T1/T2) levels. METHODS: This study retrospectively analyzed 93 cases with kinematic MRI. Cases were randomly selected from a database with inclusion criteria being no prior spine surgery and images having sufficient quality for analysis. DDD was assessed using Pfirrmann classification. Vertebral body bone marrow lesions were assessed using Modic changes. Disc height was measured at the mid-disc in neutral and extension. Translational motion and angular variation were calculated by assessing translational or angular motion segment integrity respectively in flexion and extension. Statistical associations were assessed with scatterplots and Kendall's tau. RESULTS: DDD at C7/T1 was positively associated with DDD at C6/C7 (tau = 0.53, p < 0.01) and T1/T2 (tau = 0.58, p < 0.01), with greater disc height in neutral position at T1/T2 (tau = 0.22, p < 0.01), and with greater disc height in extended position at C7/T1 (tau = 0.17, p = 0.04) and at T1/T2 (tau = 0.21, p < 0.01). DDD at C7/T1 was negatively associated with angular variation at C6/C7 (tau = - 0.23, p < 0.01). No association was appreciated between DDD at C7/T1 and translational motion. CONCLUSION: The association of DDD at the cervicothoracic junction with DDD at the adjacent levels emphasizes the necessity for careful selection of the distal level in multilevel fusion in the distal cervical spine.

Predictive factors for degenerative lumbar spinal stenosis: a model obtained from a machine learning algorithm technique.

BACKGROUND: Degenerative lumbar spinal stenosis (DLSS) is the most common spine disease in the elderly population. It is usually associated with lumbar spine joints/or ligaments degeneration. Machine learning technique is an exclusive method for handling big data analysis; however, the development of this method for spine pathology is rare. This study aims to detect the essential variables that predict the development of symptomatic DLSS using the random forest of machine learning (ML) algorithms technique. METHODS: A retrospective study with two groups of individuals. The first included 165 with symptomatic DLSS (sex ratio 80 M/85F), and the second included 180 individuals from the general population (sex ratio: 90 M/90F) without lumbar spinal stenosis symptoms. Lumbar spine measurements such as vertebral or spinal canal diameters from L1 to S1 were conducted on computerized tomography (CT) images. Demographic and health data of all the participants (e.g., body mass index and diabetes mellitus) were also recorded. RESULTS: The decision tree model of ML demonstrate that the anteroposterior diameter of the bony canal at L5 (males) and L4 (females) levels have the greatest stimulus for symptomatic DLSS (scores of 1 and 0.938). In addition, combination of these variables with other lumbar spine features is mandatory for developing the DLSS. CONCLUSIONS: Our results indicate that combination of lumbar spine characteristics such as bony canal and vertebral body dimensions rather than the presence of a sole variable is highly associated with symptomatic DLSS onset.

Do Modic changes contribute to lumbar instability or other way around? A retrospective study based on their types, extents, and affected lumbar segments.

BACKGROUND: Which types of Modic changes (MCs) and whether or how specific factors associated to MCs work on lumbar instability have yet to be well understood. The purpose of this study was to investigate the influences of the types of MCs, the extent of MCs lesion involvement, and different lumbar levels involved by MCs on lumbar instability. METHODS: This retrospective study included 263 adult subjects with MCs who underwent lumbar X-ray examinations in the neutral, flexion, and extension positions. All patients who met our inclusion criteria were examined with 1.5 Tesla magnetic resonance units. Two experienced authors with more than three-year clinical experience independently evaluated and measured the subjects' radiographic images. The subgroup analysis was performed to detect the differences in subjects' baseline characteristics and lumbar segmental motions among three types of MCs, the extent of MCs lesion involvement and different lumbar levels involved by MCs. RESULTS: There was a statistical difference in body mass index (BMI) between different involvement extent of MCs (p < 0.01), indicating that the subjects with high BMI are more likely to develop severe MCs. The subjects with Modic type 1 change (MC1) had a significant increase in lumbar angular motion than those with Modic type 2 change (MC2) and Modic type 3 change (MC3) (p < 0.01) and compared with MC3, a significant increase in lumbar translation motion was detected in subjects with MC1 and MC2 (p < 0.01). While, angular motion decreased, translation motion increased significantly as the extent of MCs lesion involvement aggravated (p < 0.01). However, there were no statistical differences in lumbar angular and translation motions between different lumbar levels involved by MCs (p > 0.05). CONCLUSIONS: Higher BMI might be a risk factor for the development of severe MCs. MC1 and MC2 significantly contribute to lumbar instability. The extents of MCs lesion involvement are strongly associated with lumbar instability. However, different lumbar levels involved by MCs have little effect on lumbar stability.

Percutaneous spine biopsy: reaching those hard-to-reach places.

Cancer is a leading cause of death, with the spine being the most common site for skeletal metastasis. The spine is also a site for primary malignancy, such as sarcoma and chordoma, as well as non-neoplastic pathologies. An accurate diagnosis of spinal neoplastic diseases is crucial in determining appropriate management. With the advent of personalised oncology, the need to establish a definitive histopathologic diagnosis to guide management is more important than ever. Percutaneous biopsy has proven to be safe and efficient in establishing a reliable histopathologic diagnosis. The spine, however, can be a challenging site to biopsy, due to the proximity of critical neurovascular, respiratory, and gastrointestinal structures. Successful spine biopsy depends on several factors: suspected diagnosis, size of the lesion, location within the spine, modality for best imaging guidance, operator experience, technical equipment considerations, and desired approach and associated limitations. The specimen must also be obtained with a biopsy route amenable to any future surgical intervention, with surgical input often sought, frequently in a multidisciplinary setting, to confirm procedure-specific goals and expectations. Knowledge of the requisite local anatomy, procedural and patient-specific indications, and contraindications and various approaches that may be used to access different segments of the spine, potential complications, and how to address these are keys to a successful percutaneous spinal biopsy, even in the most challenging of circumstances.

SOX9+ enthesis cells are associated with spinal ankylosis in ankylosing spondylitis.

OBJECTIVE: Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known. DESIGN: To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques. Enthesis cells were isolated, characterized, stimulated with TNF and/or IL-17A, and analysed by cell-based experimental tools. RESULTS: We found diffusely distributed granular tissue and cartilage in the subchondral bone in AS. Co-expression of SOX9, a specific transcription factor in cartilage, and matrix metalloproteinase 13 (MMP13) was found in the granular tissues within the subchondral bone from AS patients. Intriguingly, SOX9 expression was significantly higher in AS enthesis cells than controls and correlated with TNFR1 and IL-17RA expressions, which is important for high reactivity to TNF and IL-17A cytokines. Co-stimulation by TNF and IL-17A resulted in accelerated mineralization/calcification features, and increased OCN expression in AS enthesis cells. Furthermore, SOX9 overexpression in enthesis leads to promoting mineralization feature by TNF and IL-17A stimuli. Finally, OCN expression is elevated in the destructive enthesis of advanced AS. CONCLUSION: These findings provide insight into the links between inflammation and the mineralization of entheseal tissue as the initiation of spinal ankylosis, emphasizing the importance of SOX9+ enthesis cells.

Imaging of Spine Infections.

The incidence of spondylodiskitis has increased over the last 20 years worldwide, especially in the immunodepressed population, and it remains a complex pathology, both in terms of diagnosis and treatment. Because clinical symptoms are often nonspecific and blood culture negative, imaging plays an essential role in the diagnostic process. Magnetic resonance imaging, in particular, is the gold standard technique because it can show essential findings such as vertebral bone marrow, disk signal alteration, a paravertebral or epidural abscess, and, in the advanced stage of disease, fusion or collapse of the vertebral elements. However, many noninfectious spine diseases can simulate spinal infection. In this article, we present imaging features of specific infectious spine diseases that help radiologists make the distinction between infectious and noninfectious processes.

Optimal screw positioning in cervical pedicles to avoid complications.

BACKGROUND: Cervical instability can be caused by a variety of factors, including trauma, tumors, or infection. The cervical transpedicular screw (CPS) is one of the most modern procedures for treating cervical instability. Despite the fact that numerous innovative techniques for CPS have been proposed, the appropriate screw entry points and screw directions have yet to be thoroughly established. The aim of this study is to determine the screw insertion angles and screw entry point distances based on reference points, pedicle axis lengths, and pedicle axis intersections for each vertebra from cervical (C) C2 to C7 in both right and left by gender and age groups. METHODS: In this study, computed tomography (CT) images of patients who underwent cervical examination for any reason were evaluated retrospectively. A total of 100 patients (59 men and 41 females), ranging in age from 18 to 79 years (mean 43 years), were randomly selected for the study. Patients with a history of cervical pathology or surgery were excluded. CT images turned into 3D reconstructed images and density settings were made so that bone tissue could be best observed using OsiriX software. Pedicle axis length (PAL), pedicle transverse angle (PTA), pedicle sagittal angle (PSA), distance of screw entry point to lateral notch (DLN), distance of screw entry point to inferior articular process (DIAP), and pedicle axis intersections were measured. RESULTS: According to our findings, the optimal entry point should be 2-4 mm medial to the lateral notch and 8-12 mm superior to inferior articular process. PTA ranges between 30 to 45°, while PSA ranges between 11 to 15°. Except for the C2 pedicles, which were slightly shorter, the pedicle axis lengths (PAL) were similar from C3 to C7 in the total group. The intersection of the right and left pedicle axes was determined to be the most in C4 (51.21% in females and 72.88% in males). DISCUSSION: This study has shown that intersections of the pedicle axis must be considered in both genders, especially in C4. Standardizing optimal entry points and trajectories is crucial for improving the CPS technique's safety and effectiveness.

Standardized uptake values of 99mTc-MDP in normal vertebrae assessed using quantitative SPECT/CT for differentiation diagnosis of benign and malignant bone lesions.

BACKGROUND: Quantitative bone SPECT/CT is useful for disease follow up and inter-patient comparison. For bone metastatic malignant lesions, spine is the most commonly invaded site. However, Quantitative studies with large sample size investigating all the segments of normal cervical, thoracic and lumbar vertebrae are seldom reported. This study was to evaluate the quantitative tomography of normal vertebrae using 99mTc-MDP with SPECT/CT to investigate the feasibility of standardized uptake value (SUV) for differential diagnosis of benign and malignant bone lesions. METHODS: A retrospective study was carried out involving 221 patients (116 males and 105 females) who underwent SPECT/CT scan using 99mTc-MDP. The maximum SUV (SUVmax), mean SUV (SUVmean) and CT values (Hounsfield Unit, HU) of 2416 normal vertebrae bodies, 157 benign bone lesions and 118 malignant bone metastasis foci were obtained. The correlations between SUVmax of normal vertebrae and CT values of normal vertebrae, age, height, weight, BMI of patients were analyzed. Statistical analysis was performed with data of normal, benign and malignant groups corresponding to same sites and gender. RESULTS: The SUVmax and SUVmean of normal vertebrae in males were markedly higher than those in females (P < 0.0009). The SUVmax of each normal vertebral segment showed a strong negative correlation with CT values in both males and females (r = - 0.89 and - 0.92, respectively; P < 0.0009). The SUVmax of normal vertebrae also showed significant correlation with weight, height, and BMI in males (r = 0.4, P < 0.0009; r = 0.28, P = 0.005; r = 0.22, P = 0.026), and significant correlation with weight and BMI in females (r = 0.32, P = 0.009; r = 0.23, P = 0.031). The SUVmax of normal group, benign bone lesion group and malignant bone metastasis foci group showed statistical differences in both males and females. CONCLUSION: Our study evaluated SUVmax and SUVmean of normal vertebrae, benign bone lesion and malignant bone metastasis foci with a large sample population. Preliminary results proved the potential value of SUVmax in differentiation benign and malignant bone lesions. The results may provide a quantitative reference for clinical diagnosis and the evaluation of therapeutic response in vertebral lesions.

An Unrecognized Ligament and its Ossification in the Craniocervical Junction: Prevalence, Patient Characteristics, and Anatomic Evidence.

BACKGROUND: In the craniocervical junction, the ligaments between the anterior foramen magnum and the anterior arch of the atlas are not well defined, and ossification of the ligaments in this region has rarely been reported. Characterizing the anatomy and ossification of these ligaments may help in the diagnosis and treatment of disorders in this region. QUESTIONS/PURPOSES: (1) What is the prevalence of an unrecognized ossification at the craniocervical junction in patients with cervical spine disorders, and what are the patient characteristics associated with this ossification? (2) Do patients with this ossification have a greater risk of ossification of other structures at the craniocervical junction or cervical spine? (3) Is there an unreported ligament at this ossified site? METHODS: We conducted a retrospective study of 578 hospitalized patients who underwent CT for cervical spine disorders between January 2016 and July 2020. Based on the inclusion criteria, 11% (66 of 578) were excluded because of a cervical or craniocervical tumor, deformity, infection, fracture or dislocation, or prior surgery, leaving 89% (512 of 578) for analysis. These 512 patients had diagnoses of cervical radiculopathy, cervical myelopathy, cervical spondylotic amyotrophy, cervical spinal cord injury without a radiographic abnormality, or axial neck pain. Their mean age was 57 years (range 22-90 years), and 60% of the patients were men. Patient characteristics including age, gender, and diagnosis were retrieved from a longitudinally maintained institutional database. CT images were used to assess the presence of a previously unrecognized ossification and ossification of other structures in the craniocervical junction and cervical spine, including the posterior longitudinal ligament, anterior longitudinal ligament, nuchal ligament, ligamentum flavum, transverse ligament, and apical ligament, as well as diffuse idiopathic skeletal hyperostosis (DISH). The association between these structures was also assessed. This unreported ossification was called the capped dens sign. It was defined and graded from 1 to 3. Grade 3 was defined as the typical capped dens sign. Cervical spine MRI was used to assess whether there was an unreported structure in the same region as where the capped dens sign was detected on CT images. In the database of a recent study, there were 33 patients younger than 41 years. Nine percent (three of 33) were excluded because they did not have cervical spine MRI. MRIs of the remaining 30 patients were assessed. Their mean age was 35 years (range 22-40 years), and 58% were men. All cervical spine CT images and MRIs were reviewed by one senior spine surgeon and one junior spine surgeon twice with a 2-week interval. Blinding was accomplished by removing identifying information from the radiographs and randomly assigning them to each examiner. Any discrepancy with respect to the grade of the capped dens sign was adjudicated by a third blinded senior spine surgeon. Intrarater and interrater reliabilities were assessed by calculating weighted kappa statistics. No ligament or membrane was reported at this site. MRI is not sensitive to identify thin tissue in this region, especially when severe degeneration has occurred. A cadaveric study was conducted to discover a potential ligament between the inferior margin of the foramen magnum and the anterior arch of the atlas, as prompted by the newly discovered ossification in the clinical analysis of this study. Six embalmed human cadaveric craniocervical regions (three male and three female cadavers; median age 56 years, range 45-78 years) were dissected by a senior anatomist and a senior anatomy technician. A mid-sagittal section of the craniocervical junction was created, allowing us to explore the interval between the anterior foramen magnum and anterior arch of the atlas. A histologic analysis was conducted in two of the six cadavers (a male cadaver, 45 years; and a female cadaver, 51 years). Slides were made with 4-µm sections and stained with hematoxylin and eosin. RESULTS: A novel capped dens sign was detected in 39% (198 of 512) of the patients and the most typical capped dens sign was detected in 19% (96 of 512) of patients. The prevalence of this sign was the highest in patients with cervical spondylotic amyotrophy (12 of 25 patients). The prevalence of ossification of the anterior longitudinal ligament, ligamentum nuchae, and apical ligament, as well as DISH, was higher in patients with a capped dens sign than in those without (p = 0.04, p < 0.001, p < 0.001, and p = 0.001, respectively). The capped dens sign was identified in 69% (18 of 26) of the patients with DISH. A thin and short band-like structure or osteophyte was detected on MRI in 87% (26 of 30), in the same region as the capped dens sign. In the cadaveric study, an unreported, distinct ligamentous structure was identified at this ossified site. It originated from the posterosuperior rim of the anterior arch of the atlas to the inferior margin of the foramen magnum, which we called the inter-atlanto-occipital ligament. It was found in all six dissected craniocervical junctions. The histologic analysis revealed dense connective tissue. CONCLUSION: More than one-third of the patients in this series demonstrated CT evidence of a previously unrecognized ossification in the craniocervical junction, which we called the capped dens sign. Anatomic evidence of this sign, which was a previously unidentified ligament, was also newly discovered in this region. This study was conducted among Asian patients and specimens. Further studies among diverse ethnic groups may be needed to generalize the results. An additional well-designed prospective study will be needed to provide further evidence regarding the potential pathophysiology and clinical relevance of the capped dens sign. Furthermore, the cadaveric analysis in this study was only a preliminary report of the ligament; further biomechanical research is needed to investigate its function. CLINICAL RELEVANCE: Knowledge of this novel ligament may improve the diagnosis and treatment of craniocervical stability and dislocation. Ossification of this ligament is correlated with age, cervical spondylotic amyotrophy, and DISH. We wonder whether patients with cervical degenerative disorders who also have a capped dens sign may be at risk for the formation of osteophytes of an uncovertebral joint, which may result in palsy of the upper limb muscles. The capped dens sign may be the craniocervical manifestation of DISH. This possible association between the capped dens sign and DISH should be considered when performing surgery on patients with the capped dens sign.

Screw Malposition: Are There Long-term Repercussions to Malposition of Pedicle Screws?

BACKGROUND/INTRODUCTION: Pedicle screws have long been part of the continued advancements in spine surgery. Despite the many techniques that have been devised for their safe placement, malposition of screws continues to occur. Studies have evaluated the possible safe limits of screw malposition, and have given some insight on anatomic variation in spinal deformity. Review of the literature reveals several cases of deleterious long-term sequelae of malpositioned screws. DISCUSSION: With the current experience, proposed recommendations are provided to detect and avoid the potential long-term sequelae. Though the literature has helped to define possible concerning screws, there are no good studies predicting long-term risk. CONCLUSION: Improvements in technology and techniques, advancements in intraoperative confirmation and postoperative surveillance, studies that assist risk stratification, and expert consensus evaluations will help guide surgeons in their decision for addressing misplaced screws.

Spinal changes after craniospinal irradiation in pediatric patients.

BACKGROUND: To evaluate long-term degenerative changes in bone and soft tissue after craniospinal irradiation (CSI). PROCEDURE: An analysis was performed for 892 vertebral bodies in 220 pediatric patients treated with CSI. To analyze vertebral growth, vertebral body height was calculated. Signal changes for vertebral bodies on MRI, scoliosis and kyphosis, degenerative changes of vertebral bones and discs, and wedging or vertebral height loss were analyzed on images, and factors that influenced these changes were investigated. RESULTS: Vertebral growth was significantly correlated with radiation dose and growth hormone (GH) deficiency. Growth rate was significantly worse at a dose >39 Gy. Fatty marrow change was found in 83% of patients, 31% had disc degenerative changes, 13% had degenerative changes of spinal bones, 17% had wedging or spinal height loss, and 27% had scoliosis. CONCLUSIONS: Vertebral bone growth was significantly reduced when high doses were administered, and adequate GH replacement was important for bone growth. Even with symmetrical irradiation, the risk of scoliosis is high after CSI. There was also frequent progression of spinal demineralization and degenerative changes after CSI. Therefore, careful attention should be paid to spinal symptoms as pediatric patients grow into adulthood.

Predictive factors for positive disco-vertebral biopsy culture in pyogenic vertebral osteomyelitis, and impact of fluoroscopic versus scanographic guidance.

BACKGROUND: The aims of this study were to identify the predictive factors for microbiological diagnosis through disco-vertebral biopsy (DVB) in patients with pyogenic vertebral osteomyelitis (PVO) and negative blood cultures, and compare the performance of DVB under fluoroscopic versus scanographic guidance. METHODS: We performed a cohort study comparing positive and negative DVB among patients with PVO. All cases of PVO undergoing a DVB for microbiological diagnosis in our center were retrospectively reviewed. Infections due to Mycobacterium tuberculosis, infections on foreign device, and non-septic diseases were excluded. Anamnestic, clinical, biological, microbiological, as well as radiological data were collected from medical charts thanks to a standardized data set. RESULTS: A total of 111 patients were screened; 88 patients were included. Microbiological cultures were positive in 53/88 (60.2%) patients. A thickening of the paravertebral tissue ≥10 mm on magnetic resonance imaging (MRI) in axial MR scans was a predictive factor of DVB microbiological positivity (52.4% vs. 13.3%; p = 0.006; OR = 5.4). Overall, 51 DVB were performed under fluoroscopic guidance and 37 under scanographic guidance. Considering lumbar DVB, 25/36 (69.4%) of cases yielded positive results under fluoroscopic guidance versus 5/15 (33.3%) under scanographic guidance (p = 0.02; OR = 4.4). No adverse event linked to DVB was notified. CONCLUSION: Every patient with PVO and negative blood cultures should undergo a DVB. A thickening of the paravertebral tissue ≥10 mm on MRI is associated with a higher rate of positive DVB culture. A lumbar DVB under fluoroscopic guidance is more sensitive than under scanographic guidance to identify the micro-organism involved.

Langerhans Cell Histiocytosis With Vertebral Involvement Diagnosed and Treated Over the Last 15 Years in a Single Canadian Pediatric Academic Institution.

We report 11 children with vertebral lesion of Langerhans cell histiocytosis (LCH) diagnosed and treated between 2000 and 2015. Vertebral lesions were usually present at LCH diagnosis. No child developed neurologic symptoms. Among 29 vertebral lesions, only 2 were unstable. Chemotherapy was used in all children but 3. A LCH recurrence was observed in 6 patients, involving vertebrae in 4 cases. All children were disease-free at their last follow-up. Sequelae were more often radiologic than clinical. Since potential recurrences and incomplete bone regeneration exist, discussion about optimal treatment and long-term follow-up of vertebral lesions are essential.

Vertebral column deformity with curved cross-stitch vertebrae in Norwegian seawater-farmed Atlantic salmon, Salmo salar L.

Pathological changes in the vertebral column of farmed Atlantic salmon in Norway have been reported since the 1990s. Based on the characteristic radiographic findings, we here present a vertebral column deformity named "curved cross-stitch vertebrae" that mainly affects the middle aspect of the vertebral column. Sixty fish, from the west/northwest coast of mid-Norway, were sampled at slaughter and examined by radiography, computed tomography (CT), necropsy, macrophotography, and histology. The vertebral deformities were radiographically graded as mild, moderate, or marked. The main differences between these grades of changes were defined by increased curving of the peripheries of endplates, reduced intervertebral spaces, and vertical displacement of the vertebrae. The curved rims of endplates were located peripheral to a continuous and approximately circular borderline. The CT studies revealed small, multifocal, hypo-attenuating, round to crescent-shaped areas in the notochord, compatible with the presence of gas. Additionally, histology revealed that the axial parts of endplates had circular zones with perforations, through which either notochordal tissue prolapsed into the vertebrae or vascularized fibrochondroid proliferations extended from the vertebrae into the notochord. Inflammation was present in many vertebral bodies. To the best of our knowledge, this is the first report of gas in the notochord of fish.

Surgical Management of Spinal Disorders in People with Mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) are a group of inherited, multisystem, lysosomal storage disorders involving specific lysosomal enzyme deficiencies that result in the accumulation of glycosaminoglycans (GAG) secondary to insufficient degradation within cell lysosomes. GAG accumulation affects both primary bone formation and secondary bone growth, resulting in growth impairment. Typical spinal manifestations in MPS are atlantoaxial instability, thoracolumbar kyphosis/scoliosis, and cervical/lumbar spinal canal stenosis. Spinal disorders and their severity depend on the MPS type and may be related to disease activity. Enzyme replacement therapy or hematopoietic stem cell transplantation has advantages regarding soft tissues; however, these therapeutic modalities are not effective for bone or cartilage and MPS-related bone deformity including the spine. Because spinal disorders show the most serious deterioration among patients with MPS, spinal surgeries are required although they are challenging and associated with high anesthesia-related risks. The aim of this review article is to provide the current comprehensive knowledge of representative spinal disease in MPS and its surgical management, including the related pathology, symptoms, and examinations.

Establishment and identification of a novel HTRA1 mutation mice model.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathyis a rare form of inherited cerebral small vessel disease associated with mutations in the high-temperature requirement serine peptidase A1 gene. As of now, only about 50 cases have been reported. In 2012, our group reported a family with a novel mutant of the high-temperature requirement serine peptidase A1 gene in China for the first time. To further explore the molecular pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, a recombination mouse model expressed human high-temperature requirement serine peptidase A1 gene mutant identified by our group was generated using the Donor & Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 system and termed the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model. Results show that Mut-high-temperature requirement serine peptidase A1 geneL364P mice present similar pathological characteristics to patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, suggesting that the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model was generated successfully. Moreover, apoptosis was induced in mouse brain vascular smooth muscle cells derived from Mut-high-temperature requirement serine peptidase A1 geneL364P mice. In summary, the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy mouse model described in this study will be beneficial to demonstrate the pathological mechanism of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy and provide new therapeutic targets for clinical treatment.

An Unusual Cause of Chronic Headache in an Adolescent Boy: A Case Report.

Spontaneous intracranial hypotension (SIH) is an under-diagnosed cause of headache in children and adolescents. SIH results from cerebrospinal fluid (CSF) leak due to breach in the dura mater and the etiology for dural breach is often diverse. We report an adolescent boy who presented with chronic episodic headache that later progressed to daily headache. There was a typical history of worsening of headache on upright position and relief of headache on lying down. He was treated with migraine prophylaxis in another hospital but there was no response. Marfanoid features and brisk deep tendon reflexes were observed on clinical examination. Brain magnetic resonance imaging (MRI) revealed sagging of the brain stem, pachymeningeal enhancement, and tonsillar herniation. MRI of spine myelogram confirmed multiple levels of CSF leak. He was initially managed with supportive measures and fluoroscopic-guided fibrin glue injection. Although child remained symptom-free for the next 6 months, he again developed headache. MRI and computed tomography spine myelogram revealed a meningeal diverticulum in the lumbar spine. He was managed with an autologous epidural blood patch and he has been well since then. In this report, we highlight the clinical and radiological pointers to the presence of SIH in children with recurrent headache.

Positive Predictive Values of Lumbar Spine Magnetic Resonance Imaging Findings for Provocative Discography.

PURPOSE: The purpose of this study was to calculate the positive predictive value (PPV) of lumbar spine magnetic resonance imaging (MRI) findings for a painful disc using provocative discography. MATERIALS AND METHODS: Lumbar spine discography records and prediscography MRIs of 736 patients (2457 discs) who underwent discography for diagnostic purposes from 2003 to 2007 were retrospectively reviewed in an Institutional Review Board-exempt and Health Insurance Portability and Accountability Act-compliant protocol. Each level was identified as having high-intensity zone (HIZ) disc, disc protrusion, disc extrusion, or combination (any herniation type), disc bulge, disc degeneration, and spondylolisthesis. Statistical analysis used a 2 × 2 contingency table of significant discography results for each of the MRI variables to calculate P value and PPV with a confidence interval from a binomial distribution. RESULTS: An HIZ disc has a PPV of 0.71 (0.65-0.76, P = 4.31E - 44) for a provocative discography. A disc protrusion has a PPV of 0.79 (0.73-0.83, P = 2.68E - 53). A disc extrusion has a PPV of 0.93 (0.79-0.98, P = 1.34E - 14), a bulge of 0.43 (0.37-0.48, P = 0.002), and a degenerative disc of 0.32 (0.28-0.35, P = 0.08), and spondylolisthesis has a PPV of 0.67 (0.59-0.73, P = 1.70E - 20). A herniation of either type (extrusion or protrusion) has a PPV of 0.80 (0.75-0.84, P = 5.86E - 69). CONCLUSIONS: Disc herniations and HIZ discs have high predictive value in identifying a pain generator. An extruded disc herniation has the highest PPV for discogenic pain.