Response of the rat spinal cord to X-ray microbeams

BACKGROUND AND PURPOSE: To quantify the late dose-related responses of the rat cervical spinal cord to X-ray irradiations by an array of microbeams or by a single millimeter beam. MATERIALS AND METHODS: Necks of anesthetized rats were irradiated transversely by an 11mm wide array of 52 parallel, 35μm wide, vertical X-ray microbeams, separated by 210μm intervals between centers. Comparison was made with rats irradiated with a 1.35mm wide single beam of similar X-rays. Rats were killed when paresis developed, or up to 383days post irradiation (dpi). RESULTS: Microbeam peak/valley doses of ≈357/12.7Gy to 715/25.4Gy to an 11mm long segment of the spinal cord, or single beam doses of ≈146-454Gy to a 1.35mm long segment caused foreleg paresis and histopathologically verified spinal cord damage; rats exposed to peak/valley doses up to 253/9Gy were paresis-free at 383dpi. CONCLUSIONS: Whereas microbeam radiation therapy [MRT] for malignant gliomas implanted in rat brains can be safe, palliative or curative, the high tolerance of normal rat spinal cords to similar microbeam exposures justifies testing MRT for autochthonous malignancies in the central nervous system of larger animals with a view to subsequent clinical applications.

Rapid assessment of internodal myelin integrity in central nervous system tissue

Monitoring pathology/regeneration in experimental models of de-/remyelination requires an accurate measure not only of functional changes but also of the amount of myelin. We tested whether X-ray diffraction (XRD), which measures periodicity in unfixed myelin, can assess the structural integrity of myelin in fixed tissue. From laboratories involved in spinal cord injury research and in studying the aging primate brain, we solicited "blind" samples and used an electronic detector to record rapidly the diffraction patterns (30 min each pattern) from them. We assessed myelin integrity by measuring its periodicity and relative amount. Fixation of tissue itself introduced +/-10% variation in periodicity and +/-40% variation in relative amount of myelin. For samples having the most native-like periods, the relative amounts of myelin detected allowed distinctions to be made between normal and demyelinating segments, between motor and sensory tracts within the spinal cord, and between aged and young primate CNS. Different periodicities also allowed distinctions to be made between samples from spinal cord and nerve roots and between well-fixed and poorly fixed samples. Our findings suggest that, in addition to evaluating the effectiveness of different fixatives, XRD could also be used as a robust and rapid technique for quantitating the relative amount of myelin among spinal cords and other CNS tissue samples from experimental models of de- and remyelination.

In vivo compatibility of Dynesys(®) spinal implants: a case series of five retrieved periprosthetic tissue samples and corresponding implants

PURPOSE To determine whether particulate debris is present in periprosthetic tissue from revised Dynesys(®) devices, and if present, elicits a biological tissue reaction. METHODS Five Dynesys(®) dynamic stabilization systems consisting of pedicle screws (Ti alloy), polycarbonate-urethane (PCU) spacers and a polyethylene-terephthalate (PET) cord were explanted for pain and screw loosening after a mean of 2.86 years (1.9-5.3 years). Optical microscopy and scanning electron microscopy were used to evaluate wear, deformation and surface damage, and attenuated total reflectance Fourier transform infrared spectroscopy to assess surface chemical composition of the spacers. Periprosthetic tissue morphology and wear debris were determined using light microscopy, and PCU and PET wear debris by polarized light microscopy. RESULTS All implants had surface damage on the PCU spacers consistent with scratches and plastic deformation; 3 of 5 exhibited abrasive wear zones. In addition to fraying of the outer fibers of the PET cords in five implants, one case also evidenced cord fracture. The pedicle screws were unremarkable. Patient periprosthetic tissues around the three implants with visible PCU damage contained wear debris and a corresponding macrophage infiltration. For the patient revised for cord fracture, the tissues also contained large wear particles (>10 μm) and giant cells. Tissues from the other two patients showed comparable morphologies consisting of dense fibrous tissue with no inflammation or wear debris. CONCLUSIONS This is the first study to evaluate wear accumulation and local tissue responses for explanted Dynesys(®) devices. Polymer wear debris and an associated foreign-body macrophage response were observed in three of five cases.

Air within the spinal canal in spontaneous pneumomediastinum

Spontaneous pneumomediastinum is an uncommon benign condition that is occasionally associated with air within the spinal canal. We describe a further case in a 14-year-old girl and suggest a classification system based on a detailed review of the previous literature. Forty-eight patients with spontaneous pneumomediastinum and intraspinal air accumulation (36 men and 12 women, age range 4-72 years, median age 18 years) were grouped into those with underlying lung disease (n = 13), those with other underlying etiologic factors (n = 22), and those arising spontaneously (n = 13). Neurologic symptoms or signs were noted in one case. The remaining cases were successfully managed conservatively. In spontaneous pneumomediastinum, accumulation of air within the spinal canal is self-limiting and benign. The same management is advised in spontaneous pneumomediastinum with and without intraspinal air accumulation.

Ultrastructural changes in diaphragm neuromuscular junctions in a severe mouse model for Spinal Muscular Atrophy and their prevention by bifunctional U7 snRNA correcting SMN2 splicing

In Spinal Muscular Atrophy (SMA), the SMN1 gene is deleted or inactivated. Because of a splicing problem, the second copy gene, SMN2, generates insufficient amounts of functional SMN protein, leading to the death of spinal cord motoneurons. For a "severe" mouse SMA model (Smn -/-, hSMN2 +/+; with affected pups dying at 5-7 days), which most closely mimicks the genetic set-up in human SMA patients, we characterise SMA-related ultrastructural changes in neuromuscular junctions (NMJs) of two striated muscles with discrete functions. In the diaphragm, but not the soleus muscle of 4-days old SMA mice, mitochondria on both sides of the NMJs degenerate, and perisynaptic Schwann cells as well as endoneurial fibroblasts show striking changes in morphology. Importantly, NMJs of SMA mice in which a modified U7 snRNA corrects SMN2 splicing and delays or prevents SMA symptoms are normal. This ultrastructural study reveals novel features of NMJ alterations - in particular the involvement of perisynaptic Schwann cells - that may be relevant for human SMA pathogenesis.

Development of a documentation instrument for the conservative treatment of spinal disorders in the International Spine Registry, Spine Tango

Spine Tango is the first and only International Spine Registry in operation to date. So far, only surgical spinal interventions have been recorded and no comparable structured and comprehensive documentation instrument for conservative treatments of spinal disorders is available. This study reports on the development of a documentation instrument for the conservative treatment of spinal disorders by using the Delphi consensus method. It was conducted with a group of international experts in the field. We also assessed the usability of this new assessment tool with a prospective feasibility study on 97 outpatients and inpatients with low back or neck pain undergoing conservative treatment. The new 'Spine Tango conservative' questionnaire proved useful and suitable for the documentation of pathologies, conservative treatments and outcomes of patients with low back or neck problems. A follow-up questionnaire seemed less important in the predominantly outpatient setting. In the feasibility study, between 43 and 63% of patients reached the minimal clinically important difference in pain relief and Core Outcome Measures Index at 3 months after therapy; 87% of patients with back pain and 85% with neck pain were satisfied with the received treatment. With 'Spine Tango conservative' a first step has been taken to develop and implement a complementary system for documentation and evaluation of non-surgical spinal interventions and outcomes within the framework of the International Spine Registry. It proved useful and feasible in a first pilot study, but it will take the experience of many more cases and therapists to develop a version similarly mature as the surgical instruments of Spine Tango.

Nerve root sedimentation sign: evaluation of a new radiological sign in lumbar spinal stenosis

Retrospective case-referent study.

Preoperative mapping of arterial spinal supply using 3.0-T MR angiography with an intravasal contrast medium and high-spatial-resolution steady-state

Preoperative mapping of the arterial spinal supply prior to thoracoabdominal aortic aneurysm repair is highly relevant because of high risk for postoperative ischemic spinal cord injuries such as paraparesis or paraplegia.