Illusions of fusions: assessing cervical vertebral fusion on lateral cephalograms, multidetector computed tomographs, and cone-beam computed tomographs

INTRODUCTION The aims of this study were to compare lateral cephalograms with other radiologic methods for diagnosing suspected fusions of the cervical spine and to validate the assessment of congenital fusions and osteoarthritic changes against the anatomic truth. METHODS Four cadaver heads were selected with fusion of vertebrae C2 and C3 seen on a lateral cephalogram. Multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) were performed and assessed by 5 general radiologists and 5 oral radiologists, respectively. Vertebrae C2 and C3 were examined for osseous fusions, and the left and right facet joints were diagnosed for osteoarthritis. Subsequently, the C2 and C3 were macerated and appraised by a pathologist. Descriptive analysis was performed, and interrater agreements between and within the groups were computed. RESULTS All macerated specimens showed osteoarthritic findings of varying degrees, but no congenital bony fusion. All observers agreed that no fusion was found on MDCT or CBCT. They disagreed on the prevalence of osteoarthritic deformities (general radiologists/MDCT, 100%; oral radiologists/CBCT, 93.3%) and joint space assessment in the facet joints (kappa = 0.452). The agreement within the rater groups differed considerably (general radiologists/MDCT, kappa = 0.612; oral radiologists/CBCT, kappa = 0.240). CONCLUSIONS Lateral cephalograms do not provide dependable data to assess the cervical spine for fusions and cause false-positive detections. Both MDCT interpreted by general radiologists and CBCT interpreted by oral radiologists are reliable methods to exclude potential fusions. Degenerative osteoarthritic changes are diagnosed more accurately and consistently by general radiologists evaluating MDCT.

Comparison of the biomechanical properties of a ventral cervical intervertebral anchored fusion device with locking plate fixation applied to cadaveric canine cervical spines

OBJECTIVE: To evaluate fixation properties of a new intervertebral anchored fusion device and compare these with ventral locking plate fixation. STUDY DESIGN: In vitro biomechanical evaluation. ANIMALS: Cadaveric canine C4-C7 cervical spines (n = 9). METHODS: Cervical spines were nondestructively loaded with pure moments in a nonconstraining testing apparatus to induce flexion/extension while angular motion was measured. Range of motion (ROM) and neutral zone (NZ) were calculated for (1) intact specimens, (2) specimens after discectomy and fixation with a purpose-built intervertebral fusion cage with integrated ventral fixation, and (3) after removal of the device and fixation with a ventral locking plate. RESULTS: Both fixation techniques resulted in a decrease in ROM and NZ (P < .001) compared with the intact segments. There were no significant differences between the anchored spacer and locking plate fixation. CONCLUSION: An anchored spacer appears to provide similar biomechanical stability to that of locking plate fixation.

Far lateral lumbar disc extrusion: MRI findings and surgical treatment

This case report describes the magnetic resonance imaging (MRI) findings and the treatment of a far lateral extrusion of disc material at the sixth and seventh lumbar vertebrae (L6-L7) in a five-year-old male Alpine Dachsbracke dog referred to our hospital for investigation of the complaint of a one week progressive lameness in the left pelvic limb and poorly localized back pain. An extra-foraminal left lateral disc herniation impinging on the sixth lumbar nerve root was diagnosed by MRI examinations. Due to the far lateral position of the extruded disc material on MRI, surgical opening of the spinal canal was not necessary. Removal of the herniated soft disc material impinging on the L6 nerve root, and fenestration of the L6-L7 disc was performed laterally. To the author's knowledge 'far-lateral' disc herniation beyond the neuroforamen without any spinal canal contact has not been described in dogs until now. A complete recovery with no evidence of pain was achieved only after a couple of weeks after surgery. We acknowledge that it is possible that other pathological mechanisms may have contributed to clinical signs and to a delayed recovery.

Structural rearrangements of the central region of the morbillivirus attachment protein stalk domain trigger F protein refolding for membrane fusion

It is unknown how receptor binding by the paramyxovirus attachment proteins (HN, H, or G) triggers the fusion (F) protein to fuse with the plasma membrane for cell entry. H-proteins of the morbillivirus genus consist of a stalk ectodomain supporting a cuboidal head; physiological oligomers consist of non-covalent dimer-of-dimers. We report here the successful engineering of intermolecular disulfide bonds within the central region (residues 91-115) of the morbillivirus H-stalk; a sub-domain that also encompasses the putative F-contacting section (residues 111-118). Remarkably, several intersubunit crosslinks abrogated membrane fusion, but bioactivity was restored under reducing conditions. This phenotype extended equally to H proteins derived from virulent and attenuated morbillivirus strains and was independent of the nature of the contacted receptor. Our data reveal that the morbillivirus H-stalk domain is composed of four tightly-packed subunits. Upon receptor binding, these subunits structurally rearrange, possibly inducing conformational changes within the central region of the stalk, which, in turn, promote fusion. Given that the fundamental architecture appears conserved among paramyxovirus attachment protein stalk domains, we predict that these motions may act as a universal paramyxovirus F-triggering mechanism.

Increasing the Antitumor Effect of an EpCAM-Targeting Fusion Toxin by Facile Click PEGylation

Fusion toxins used for cancer-related therapy have demonstrated short circulation half-lives, which impairs tumor localization and, hence, efficacy. Here, we demonstrate that the pharmacokinetics of a fusion toxin composed of a designed ankyrin repeat protein (DARPin) and domain I–truncated Pseudomonas Exotoxin A (PE40/ETA″) can be significantly improved by facile bioorthogonal conjugation with a polyethylene glycol (PEG) polymer at a unique position. Fusion of the anti-EpCAM DARPin Ec1 to ETA″ and expression in methionine-auxotrophic E. coli enabled introduction of the nonnatural amino acid azidohomoalanine (Aha) at position 1 for strain-promoted click PEGylation. PEGylated Ec1-ETA″ was characterized by detailed biochemical analysis, and its potential for tumor targeting was assessed using carcinoma cell lines of various histotypes in vitro, and subcutaneous and orthotopic tumor xenografts in vivo. The mild click reaction resulted in a well-defined mono-PEGylated product, which could be readily purified to homogeneity. Despite an increased hydrodynamic radius resulting from the polymer, the fusion toxin demonstrated high EpCAM-binding activity and retained cytotoxicity in the femtomolar range. Pharmacologic analysis in mice unveiled an almost 6-fold increase in the elimination half-life (14 vs. 82 minutes) and a more than 7-fold increase in the area under the curve (AUC) compared with non-PEGylated Ec1-ETA″, which directly translated in increased and longer-lasting effects on established tumor xenografts. Our data underline the great potential of combining the inherent advantages of the DARPin format with bioorthogonal click chemistry to overcome the limitations of engineering fusion toxins with enhanced efficacy for cancer-related therapy.

Mechanism for active membrane fusion triggering by morbillivirus attachment protein.

The paramyxovirus entry machinery consists of two glycoproteins that tightly cooperate to achieve membrane fusion for cell entry: the tetrameric attachment protein (HN, H, or G, depending on the paramyxovirus genus) and the trimeric fusion protein (F). Here, we explore whether receptor-induced conformational changes within morbillivirus H proteins promote membrane fusion by a mechanism requiring the active destabilization of prefusion F or by the dissociation of prefusion F from intracellularly preformed glycoprotein complexes. To properly probe F conformations, we identified anti-F monoclonal antibodies (MAbs) that recognize conformation-dependent epitopes. Through heat treatment as a surrogate for H-mediated F triggering, we demonstrate with these MAbs that the morbillivirus F trimer contains a sufficiently high inherent activation energy barrier to maintain the metastable prefusion state even in the absence of H. This notion was further validated by exploring the conformational states of destabilized F mutants and stabilized soluble F variants combined with the use of a membrane fusion inhibitor (3g). Taken together, our findings reveal that the morbillivirus H protein must lower the activation energy barrier of metastable prefusion F for fusion triggering.

Fatal alveolar echinococcosis of the lumbar spine

For the last 10 years, the southern part of Belgium has been recognized as a low-risk area of endemicity for alveolar echinococcosis. This infection, caused by Echinococcus multilocularis, usually induces a severe liver condition and can sometimes spread to other organs. However, alveolar echinococcosis involving bones has been described only very rarely. Here, a fatal case of spondylodiscitis due to E. multilocularis contracted in southern Belgium is reported.

Histomorphometric and Radiographical Changes After Lumbar Implantation of the PEEK Nonfusion Interspinous Device in the BB.4S Rat Model

Study Design. An experimental animal study. Objective. To investigate histomorphometric and radiographical changes in the BB.4S rat model after PEEK (polyetheretherketone) nonfusion interspinous device implantation. Summary of Background Data. Clinical effectiveness of the PEEK nonfusion spine implant Wallis (Abbott, Bordeaux, France; now Zimmer, Warsaw, IN) is well documented. However, there is a lack of evidence on the long-term effects of this implant on bone, in particular its influence on structural changes of bone elements of the lumbar spine. Methods. Twenty-four male BB.4S rats aged 11 weeks underwent surgery for implantation of a PEEK nonfusion interspinous device or for a sham procedure in 3 groups of 8 animals each: 1) implantation at level L4–L5; 2) implantation at level L5–L6; and 3) sham surgery. Eleven weeks postoperatively osteolyses at the implant-bone interface were measured via radiograph, bone mineral density of vertebral bodies was analyzed using osteodensitometry, and bone mineral content as well as resorption of the spinous processes were examined by histomorphometry. Results. Resorption of the spinous processes at the site of the interspinous implant was found in all treated segments. There was no significant difference in either bone density of vertebral bodies or histomorphometric structure of the spinous processes between adjacent vertebral bodies, between treated and untreated segments and between groups. Conclusion. These findings indicate that resorption of spinous processes because of a result of implant loosening, inhibit the targeted load redistribution through the PEEK nonfusion interspinous device in the lumbar spinal segment of the rat. This leads to reduced long-term stability of the implant in the animal model. These results suggest that PEEK nonfusion interspinous devices like the Wallis implants may have time-limited effects and should only be used for specified indications.

Increased intraoperative epidural pressure in lumbar spinal stenosis patients with a positive nerve root sedimentation sign

Purpose The sedimentation sign (SedSign) has been shown to discriminate well between selected patients with and without lumbar spinal stenosis (LSS). The purpose of this study was to compare the pressure values associated with LSS versus non-LSS and discuss whether a positive SedSign may be related to increased epidural pressure at the level of the stenosis. Methods We measured the intraoperative epidural pressure in five patients without LSS and a negative SedSign, and in five patients with LSS and a positive SedSign using a Codman TM catheter in prone position under radioscopy. Results Patients with a negative SedSign had a median epidural pressure of 9 mmHg independent of the measurement location. Breath and pulse-synchronous waves accounted for 1–3 mmHg. In patients with monosegmental LSS and a positive SedSign, the epidural pressure above and below the stenosis was similar (median 8–9 mmHg). At the level of the stenosis the median epidural pressure was 22 mmHg. A breath and pulse-synchronous wave was present cranial to the stenosis, but absent below. These findings were independent of the cross-sectional area of the spinal canal at the level of the stenosis. Conclusions Patients with LSS have an increased epidural pressure at the level of the stenosis and altered pressure wave characteristics below. We argue that the absence of sedimentation of lumbar nerve roots to the dorsal part of the dural sac in supine position may be due to tethering of affected nerve roots at the level of the stenosis.