Secukinumab in patients with psoriatic arthritis and axial manifestations: results from the double-blind, randomised, phase 3 MAXIMISE trial.

OBJECTIVES: MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial manifestations of psoriatic arthritis (PsA). METHODS: This phase 3b, double-blind, placebo-controlled, multi-centre 52-week trial included patients (≥18 years) diagnosed with PsA and classified by ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria, with spinal pain Visual Analogue Score ≥40/100 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite use of at least two non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomised (1:1:1) to secukinumab 300 mg, secukinumab 150 mg or placebo weekly for 4 weeks and every 4 weeks thereafter. At week 12, placebo patients were re-randomised to secukinumab 300/150 mg. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society) response with secukinumab 300 mg at week 12. RESULTS: Patients were randomly assigned; 167 to secukinumab 300 mg, 165 to secukinumab 150 mg and 166 to placebo. Secukinumab 300 mg and 150 mg significantly improved ASAS20 response versus placebo at week 12 (63% and 66% vs 31% placebo). The OR (95% CI) comparing secukinumab 300 mg and 150 mg versus placebo, using a logistic regression model after multiple imputation, was 3.8 (2.4 and 6.1) and 4.4 (2.7 and 7.0; p<0.0001). CONCLUSIONS: Secukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs. TRIAL REGISTRATION NUMBER: NCT02721966.

Tendinitis calcificante del musculo largo del cuello: presentación de un caso clínico / Calcific tendinitis of the longus colli muscle: a case report / Tendinite calcificante do músculo longo do pescoço: apresentação de um caso clínico

La tendinitis calcificante del músculo largo del cuello es una patología subdiagnsoticada, de baja frecuencia, autolimitada. Se presenta clínicamente como una de las causas de odinofagia en la consulta médica. Se produce debido al depósito de cristales de hidroxiapatita en espacio retrofaríngeo, desencadenándose una respuesta inflamatoria local. En la TMLC el principal diagnóstico diferencial es el absceso retrofaríngeo, ya que puede presentarse clínicamente con odinofagia, disfagia , disminución de la movilidad del cuello y cervicalgia. En nuestro trabajo se analiza un caso clínico sobre dicha patología, en un hombre de 45 años; realizando un análisis de la sintomatología, diagnóstico y tratamiento de esta entidad.

Calcific tendinitis of the long neck muscle is an underdiagnosed, low frequency, self-limited pathology. It is clinically presented as one of the causes of odynophagia in the medical consultation. It occurs due to the deposit of hydroxyapatite crystals in the retropharyngeal space, triggering a local inflammatory response. On This patholgy, the main differential diagnosis is retropharyngeal abscess, since it can present clinically with odynophagia, dysphagia, decreased mobility of the neck, and neck pain. In our work, a clinical case of this pathology is analyzed, in a 45-year-old man; performing an analysis of the symptoms, diagnosis and treatment of this entity.

A tendinite calcificante do músculo longo do pescoço é uma patologia subdiagnsoticada, de baixa frequência, autolimitada. Apresenta-se clinicamente como uma das causas de odinofagia na consulta médica. Ocorre devido ao depósito de cristais de hidroxiapatita em espaço retrofaríngeo, desencadeando-se uma resposta inflamatória local. Na TMLC o principal diagnóstico diferencial é o abscesso retrofaríngeo, já que pode apresentar-se clinicamente com odinofagia, disfagia , diminuição da mobilidade do pescoço e cervicalgia. Em nosso trabalho analisa-se um caso clínico sobre essa patologia, em um homem de 45 anos; realizando uma análise da sintomatologia, diagnóstico e tratamento desta entidade.

Chondrosarcoma in the body of the C2 vertebral axis.

Chondrosarcoma, a malignant bone tumor, is rarely encountered in the cervical spine. This article describes a patient whose neck pain and dysphagia were caused by an expansive, destructive lesion with calcification that was located in the body of the axis (C2 vertebra), the first time a chondrosarcoma has been reported in this location.

Surgical Fixation Using Screw-Rod Construct Instrumentation for Upper Cervical Instability in Pediatric Down Syndrome Patients.

STUDY DESIGN: Retrospective case series. OBJECTIVES: To describe the indications and outcomes of cervical fixation using modern instrumentation in a case series of pediatric Down syndrome (DS) patients. SUMMARY OF BACKGROUND DATA: Cervical instability is the major cervical spine concern in children with DS. Although fixation techniques have advanced over the past quarter-century, the outcome of fixation with modern instrumentation for upper cervical instability in DS patients has not been thoroughly investigated. METHODS: We searched the orthopedic database at our institution for patients with a diagnosis of DS who had undergone a cervical spine fusion between 2006 and 2017. Patient demographics, diagnoses, surgical indications, surgical details, and complications were recorded. Preoperative imaging was reviewed to determine atlanto-dens intervals and spinal cord signal changes. Postoperative radiographs or CT scans were reviewed to determine union. RESULTS: Twelve DS patients met our inclusion criteria. The mean age at surgery was 9.3 years (range 3.8-18.8 years). Patients with secondary causes of instability included 7 patients with os odontoideum and 1 patient with a pars fracture. Three patients (25%) were identified on asymptomatic screening, with none of these having cord signal changes on magnetic resonance imaging (MRI). Modern implants (screws, plates, cages) were used in every patient in our series. The mean number of levels fused was 1.9 (range 1-5). The overall complication rate was 41.7% (5/12). Four patients required repeat surgery for nonunion. All patients with adequate radiographic follow-up demonstrated union (11/11, 100%). One patient was lost to follow-up. CONCLUSIONS: Fixation for cervical instability is a critical component of the management of DS. A minority of patients receiving surgery were identified through asymptomatic screening. There was a high complication risk associated with surgery in our study; however, the addition of rigid fixation has lessened the complication rate compared with previous studies. LEVEL OF EVIDENCE: Level IV.

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

OBJECTIVES: To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). METHODS: Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. RESULTS: A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). CONCLUSION: TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.

Reduction of atlantoaxial dislocation prevented by pathological position of the transverse ligament in fixed, irreducible os odontoideum: operative illustrations and radiographic correlates in 41 patients.

OBJECTIVE Os odontoideum (OO) is a craniovertebral junction (CVJ) abnormality in which an ossicle (small bone) is cranial to a hypoplastic dens by a variable gap. This abnormality can result in instability, which may be reducible or irreducible. What leads to irreducibility in OO is unclear. Therefore, the authors sought to better understand the causes of irreducibility in OO. METHODS A retrospective review was conducted, which identified more than 200 patients who had undergone surgical treatment for OO between 1978 and 2015 at the University of Iowa Hospitals and Clinics. Only the 41 patients who had irreducible OO were included in this study. All inpatient and outpatient records were retrospectively reviewed, and patient demographics, clinical presentation, radiographic findings, surgical treatment, and operative findings were recorded and analyzed. RESULTS The cohort of 41 patients who were found to have irreducible OO included both children and adults. A majority of patients were adults (61% were 18 years or older). Clinical presentation included neck pain and headache in the majority of patients (93%). Weakness, sensory disturbances, and myelopathy were invariably present in all 41 patients (100%). Down syndrome was much more common in the pediatric cohort than in the adult cohort; of the 16 pediatric patients, 6 had Down syndrome (38%), and none of the adults did. Of the 16 pediatric patients, 5 had segmentation failure (31%) in the subaxial spine, and none of the adults did. A form of atlantoaxial dislocation was seen in all cases. On CT imaging, atlantoaxial facets were dislocated in all 41 cases but did not have osseous changes that would have prevented reduction. On MRI, the transverse ligament was identified anterior and inferior to the ossicle and superior to the hypoplastic odontoid process in all cases in which these studies were available (i.e., post-MRI era; 36 of 36 cases). The ligament was hypointense on T2-weighted images but also had an associated hyperintense signal on T2 images. Intraoperatively, the transverse ligament was identified anterior and inferior to the ossicle and superior to the hypoplastic odontoid process in all 41 cases. CONCLUSIONS In the largest series to date of irreducible OO and the only study to examine variable factors that lead to irreducibility in OO, the authors found that the position of the transverse ligament anterior and inferior to the ossicle is the most common factor in the irreducibility of OO. The presence of granulation tissue and of the dystopic variant of OO is also associated with irreducibility. The presence of Down syndrome and segmentation failure probably leads to faster progression of ligamentous incompetence and therefore earlier presentation of instability and irreducibility. This is the first study in which intraoperative findings regarding the transverse ligament have been correlated with MRI.

10 kHz High-Frequency Spinal Cord Stimulation for Chronic Axial Low Back Pain in Patients With No History of Spinal Surgery: A Preliminary, Prospective, Open Label and Proof-of-Concept Study.

OBJECTIVE: To explore the effectiveness of 10 kHz high frequency spinal cord stimulation (HF10 therapy) treatment of chronic low back pain in patients who have not had spinal surgery. METHODS: Patients with chronic low back pain without prior spinal surgery were evaluated by a team of spine surgeons to rule out any spinal pathology amenable to surgical interventions and by a multidisciplinary pain team to confirm eligibility for the study. After a successful (>50% back pain reduction) trial of HF10 therapy, enrolled subjects underwent permanent system implantation and were followed-up one year post-implant. RESULTS: About 95% of the enrolled subjects (20/21) received the permanent system. At 12 months post-implant, both back pain VAS score and ODI were significantly reduced compared with baseline values (by 73% and 48%, respectively); an estimated quality-adjusted life year gain of 0.47 and a reduction in opioid use by 64% was observed. Four more patients among those unable to work at baseline due to back pain were employed at 12 months post-implant. There were no serious adverse events. CONCLUSION: HF10 therapy may provide significant back pain relief, reduction in disability, improvement quality of life, and reduction in opioid use in chronic low back pain not resulting from spinal surgery.

Cervical Spine pain as a presenting complaint in metastatic pancreatic cancer: a case report.

A 48 year-old female presented to her primary care physician with a two-month history of neck pain with negative cervical spine x-rays. During that office visit, the patient was noted to be tachycardic with EKG revealing ST depressions, which led to hospital admission. Acute coronary syndrome was ruled out, however, persistent neck pain warranted inpatient MRI of the cervical spine, which revealed a cervical spine lesion. Extensive investigation and biopsy ultimately confirmed stage IV pancreatic adenocarcinoma with metastases to the bone, liver, and likely lung. In the literature, the findings of a primary metastatic site being bone is rare with only a few case reports showing vertebral or sternal metastasis as the first clinical manifestation of pancreatic cancer. The uniqueness of this case lies in the only presenting complaint being cervical spine pain in the setting of extensive metastases to the liver, bone, and likely lung.

In vivo pre-activation of monocytes in patients with axial spondyloarthritis.

INTRODUCTION: Innate immune responses, including monocyte functions, seem to play an important role in the pathogenesis of axial spondyloarthritis (axSpA). Therefore, we characterized the phenotype and functional state of monocytes of patients with axSpA. METHODS: Fifty-seven patients with axSpA, 11 patients with rheumatoid arthritis (RA), and 29 healthy controls were included in the study. We determined the percentage of classic, intermediate, and non-classic monocytes according to CD14 and CD16 expression and the expression of Toll-like receptor (TLR) 1, 2, and 4 in whole blood by flow cytometry. The percentage of monocytes producing interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNFα), IL-12/23p40, and IL-1 receptor antagonist (IL-1ra) was detected by flow cytometry after stimulation of whole blood without and with different TLR and nucleotide-binding oligomerization domain ligands-i.e., lipopolysaccharide (LPS), fibroblast-stimulating lipopeptid-1, PAM3CSK4, and muramyl dipeptide (MDP)-for 5 h. IL-10 production was measured after 18 h of stimulation in supernatants by enzyme-linked immunosorbent assay. RESULTS: In patients with axSpA but not patients with RA, we found higher frequencies of classic monocytes than in controls (median of 90.4% versus 80.4%, P < 0.05), higher frequencies of monocytes spontaneously producing IL-1beta and IL-1ra (P < 0.05), and a higher percentage of monocytes producing IL-1beta after MDP stimulation (P < 0.05). Elevated cytokine production was confined to axSpA patients under conventional therapy (non-steroidal anti-inflammatory drugs) and not found in patients under TNFα inhibitor treatment. The LPS-induced production of IL-6 and IL-10 was lower in axSpA patients compared with controls (P < 0.05). Monocytic TLR expression was unaffected in patients with axSpA. CONCLUSION: Enhanced spontaneous and MDP-induced cytokine secretion by monocytes suggests in vivo pre-activation of monocytes in axSpA patients under conventional therapy which is reverted under TNF inhibitor treatment.

Advances in classification, basic mechanisms and clinical science in ankylosing spondylitis and axial spondyloarthritis.

The field of spondyloarthritis (SpA) has seen huge advances over the past 5 years. The classification of axial disease has been redefined by the axial SpA criteria that incorporate disease captured before radiographic damage is evident as well as established erosive sacroiliac joint disease. Our knowledge of genetics and basic immunological pathways has progressed significantly. In addition, revolutionary progress has been achieved with the availability of tumour necrosis factor inhibitors for treating patients with moderate to severe disease. In parallel, several of novel biomarkers have been identified that show significant promise for the future. Advances in magnetic resonance imaging have helped define positive disease. We have identified that T1 and short tau inversion recovery sequences are best for the diagnosis of axial SpA, and gadolinium contrast is not additive for diagnosis. Progress has been made in identifying potential agents and strategies that reduce radiographic progression. Several referral strategies aimed at appropriate identification of patients have been trialled and found to be effective. There is still substantial work ahead, but the advances of the last 5 years have made a huge and tangible difference at the clinical coalface, and we suggest that this trend will continue.

Treatment of C-2 metastatic tumors with intraoperative transoral or transpedicular vertebroplasty and occipitocervical posterior fixation.

OBJECT: Metastatic spinal tumors of the atlantoaxial region are quite uncommon, and surgery is challenging. The aim in this study was to evaluate the safety and efficacy of transoral or transpedicular vertebroplasty combined with posterior fixation in C-2 metastatic disease. METHODS: The authors collected from a hospital database all cases of C-2 metastatic tumor treated in the period from January 2009 to December 2012. Cases with histologically confirmed metastatic disease were included, but those with epidural tumorous propagation and signs of spinal cord compression were excluded. RESULTS: Five patients (3 females, 2 males) with osteolytic C-2 metastasis were eligible for this study. In 3 cases a purely posterior approach was taken to perform a dorsal open C-2 biopsy and transpedicular vertebroplasty followed by posterior occipitocervical fixation. In the other 2 cases a transoral C-2 biopsy and vertebroplasty were performed in combination with dorsal occipitocervical fixation during the same operative session. Patients were followed up with regular fluoroscopy, MRI, and CT studies as well as neurological examinations. During an average follow-up of 13 months (range 8-19 months), no surgical or neurological complications were associated with this combined approach. In all cases spinal stability and pain reduction were detected. The average pain score according to the visual analog scale was 3.5 after surgery (range 2-5); before surgery, the average score was 7 (range 6-8). The average volume of polymethylmethacrylate injected was 4 ml. The body and dens of the C-2 vertebra was filled more than 60% for each patient. CONCLUSIONS: In this small series, simultaneous intraoperative transoral or transpedicular vertebroplasty and dorsal occipitocervical fixation proved to be a safe and effective treatment for patients with osteolytic C-2 metastatic tumors. These techniques may provide excellent pain relief and improvements in quality of life. The true value of these combined techniques should be evaluated in larger series.

Holospinal epidural abscess of the spinal axis: two illustrative cases with review of treatment strategies and surgical techniques.

Despite the increasing prevalence of spinal infections, the subcategory of holospinal epidural abscesses (HEAs) is extremely infrequent and requires unique management. Panspinal imaging (preferably MRI), modern aggressive antibiotic therapy, and prompt surgical intervention remain the standard of care for all spinal axis infections including HEAs; however, the surgical decision making on timing and extent of the procedure still remain ill defined for HEAs. Decompression including skip laminectomies or laminoplasties is described, with varied clinical outcomes. In this review the authors present the illustrative cases of 2 patients with HEAs who were treated using skip laminectomies and epidural catheter irrigation techniques. The discussion highlights different management strategies including the role of conservative (nonsurgical) management in these lesions, especially with an already identified pathogen and the absence of mass effect on MRI or significant neurological defects. Among fewer than 25 case reports of HEA published in the past 25 years, the most important aspect in deciding a role for surgery is the neurological examination. Nearly 20% were treated successfully with medical therapy alone if neurologically intact. None of the reported cases had an associated cranial infection with HEA, because the dural adhesion around the foramen magnum prevented rostral spread of infection. Traditionally a posterior approach to the epidural space with irrigation is performed, unless an extensive focal ventral collection is causing cord compression. Surgical intervention for HEA should be an adjuvant treatment strategy for all acutely deteriorating patients, whereas aspiration of other infected sites like a psoas abscess can determine an infective pathogen, and appropriate antibiotic treatment may avoid surgical intervention in the neurologically intact patient.

Primary atlantoaxial bone tumors in children: management strategies and long-term follow-up.

OBJECT: Atlantoaxial tumors account for a substantial proportion of primary bone tumors in children. Before resection, surgeons must consider the complex regional anatomy, the potential for neurological compromise, craniocervical instability, and the question of tumor resectability in a growing spine. Using current technology, the authors analyzed surgical cases in this light and present outcomes and treatment recommendations after long-term patient follow-up. METHODS: The authors reviewed clinical records for 23 children whose primary atlantoaxial bone tumors were treated from 1996 through 2010. RESULTS: Pathological lesions among the 23 patients were 4 aneurysmal bone cysts, 2 osteochondromas, 5 chordomas, 4 osteoblastomas, 3 fibrous dysplasias, 4 eosinophilic granulomas, and 1 Ewing's sarcoma. Clinical presentation consisted of neck pain (n = 23), headaches and occipital pain (n = 16), myelopathy (n = 8), and torticollis (n = 4). Selective angiography and coil embolization were undertaken for all patients with aneurysmal bone cysts and osteoblastomas, 2 patients with chordomas, 1 patient with fibrous dysplasia, and 1 patient with Ewing's sarcoma. Primary embolization treatment of radiation-induced aneurysmal bone cyst of the atlas showed complete reossification. Results of CT-guided needle biopsy were diagnostic for 1 patient with eosinophilic granuloma and 1 with Ewing's sarcoma. Needle biopsies performed before referral were associated with extreme blood loss for 1 patient and misdiagnosis for 2 patients. Surgery involved lateral extrapharyngeal, transoral, posterior, and posterolateral approaches with vertebral artery rerouting. Complete resection was possible for 9 patients (2 with osteochondroma, 3 with fibrous dysplasia, 2 with chordoma, and 2 with osteoblastoma). Decompression and internal fusion were performed for 3 patients with aneurysmal bone cysts. Of the 23 patients, 7 underwent dorsal fusion and 4 underwent ventral fusion of the axis body. Chemotherapy was necessary for the patients with eosinophilic granuloma with multifocal disease and for the patient with Ewing's sarcoma. There was no morbidity, and there were no deaths. All patients with benign lesions were free of disease at the time of the follow-up visit (mean ± SD follow-up 8.8 ± 1.1 years; range 2-18 years). Chordomas received proton or LINAC irradiation, and as of 4-15 years of follow-up, no recurrence has been noted. CONCLUSIONS: Because most atlantoaxial tumors in children are benign, an intralesional procedure could suffice. Vascular control and staged resection are critical. Ventral transoral fusion or lateral extrapharyngeal fusion has been successful. Resection with ventral fusion and reconstruction are essential for vertebral body collapse. Management of eosinophilic granulomas must be individualized and might require diagnosis through needle biopsy.

A very rare cause of neck pain: primary Ewing sarcoma of the axis.

We report the case of a 7-year-old boy who presented with a 1-month history of neck pain, left-sided torticollis, and no neurological deficit. Computed tomography and magnetic resonance imaging revealed an expansile lesion in the axis, with epidural and prevertebral soft tissue components. Histopathologic examination of the biopsy specimen revealed primary vertebral Ewing sarcoma. This is the first case of primary vertebral Ewing sarcoma that has presented with torticollis. It is essential for physicians to be familiar with this condition and the associated imaging findings because early diagnosis of such cases is the key to better prognosis.

Cervical myelopathy caused by invagination of anomalous lamina of the axis.

The authors report a case of cervical myelopathy caused by invagination of the bilaterally separated lamina of the axis. They also present a literature review. The patient was a previously healthy 68-year-old man with a 1-year history of slowly progressive gait disturbance, right-hand clumsiness, and right dominant sensory disturbance in his trunk and extremities. Both MRI and CT showed that the spinal cord was markedly compressed at the C2-3 level, on the right side, by a deeply invaginated anomalous lamina of the axis. A bilaterally separated lamina was also visible. The patient underwent removal of the anomalous invaginated fragment of the separated lamina and the spinous process of the axis. One year after surgery, his myelopathic symptoms had almost completely resolved. Here, the authors present the case of a patient with an extremely rare anomaly of the lamina of the axis. The underlying pathogenesis of this anomaly could be the failure of the 2 chondrification centers on either side to fuse into a single ossification center. Surgical removal of the anomalous invaginated lamina produced a satisfactory outcome.

Percutaneous vertebroplasty of the C2 body and dens using the anterior oblique ascending transdiscal approach.

This first description of percutaneous vertebroplasty (PVP) of the second cervical vertebra (C2) using an ascending oblique transdiscal approach is a case report of a 63-year-old woman who complained of neck pain that was resistant to painkillers and the result of an osteolytic metastatic lesion of C2. PVP was performed using an ascending oblique transdiscal approach, a percutaneous technique that had never been described before. It has since been used in more than 15 patients, resulting in pain relief and stabilization of C2 with good distribution of cement across the vertebral body and dens. Also, there were no complications and no leakage of cement along the path of the needle.