Andrew T. Dailey

Differential Macrophage Responses in the Peripheral and Central Nervous System during Wallerian Degeneration of Axons

We characterized quantitatively the macrophage response following axonal injury in both the peripheral (PNS) and central nervous system (CNS) of adult mammals. A monoclonal antibody (ED-1) which stains monocytes, macrophages, and activated microglia was employed. In one model, Wallerian degeneration of the sciatic nerve was studied. An increase in the number of macrophages was seen as early as 1 day following nerve transection. Macrophage number increased synchronously along the length of degenerating nerve over a 21-day period. In a second model, transection of a spinal dorsal sensory root allowed us to compare and contrast the macrophage response along the PNS and CNS portions of a single axonal pathway. An increased number of macrophages restricted to the PNS portion of this pathway was seen by 3 days and continued to increase over a 14-day period. Myelin breakdown occurred in association with an increase in the number of macrophages by 3 days in the PNS but not the CNS portion of the degenerating dorsal root axon pathway. Low-affinity nerve growth factor receptor immunohistochemical staining increased by Day 1 in the PNS but not the CNS portion of this pathway, occurring prior to the invasion of macrophages. In both models, the morphology of infiltrating macrophages changed over time from small slender ramified cells to large elongated multivacuolated cells. In conclusion, our results demonstrate that the macrophage response during Wallerian degeneration of axons in adult mammals is much more rapid and robust in the PNS, where axonal regeneration occurs, than in the CNS, where axonal regeneration is far more limited.

Magnetic resonance neurography of peripheral nerve degeneration and regeneration

1To date, no study has shown that this technique can visualise the process of peripheral nerve degeneration and regeneration over time. We show how MRN signal changes during degeneration and regeneration of an injured peripheral nerve correlated with clinical and electrodiagnostic findings. A 29-year-old man had a traumatic laceration of the right sciatic nerve in the lower thigh resulting in an inability to dorsiflex and evert his right foot. Emergency surgery documented complete transection of the peroneal nerve which was surgically anastomosed. On referral 2 months later, clinical and electrodiagnostic examinations confirmed complete denervation of all muscles supplied by this nerve. Follow-up examinations 4 and 6 months after the injury showed no reinnervation of these muscles. MRN images were obtained on a 1·5-Tesla scanner (Signa; General Electric, Milwaukee, WI) with custom-designed phasedarray coils and imaging protocols previously described: 1

Risk Factors for Respiratory Failure Following Operative Stabilization of Thoracic and Lumbar Spine Fractures

BACKGROUND Respiratory failure is a serious complication that can adversely affect the hospital course and survival of multiply injured patients. Some studies have suggested that delayed surgical stabilization of spine fractures may increase the incidence of respiratory complications. However, the authors of these studies analyzed small sets of patients and did not assess the independent effects of multiple risk factors. METHODS A retrospective cohort study was conducted at a regional level-I trauma center to identify risk factors for respiratory failure in patients with surgically treated thoracic and lumbar spine fractures. Demographic, diagnostic, and procedural variables were identified. The incidence of respiratory failure was determined in an adult respiratory distress syndrome registry maintained concurrently at the same institution. Univariate and multivariate analyses were used to determine independent risk factors for respiratory failure. An algorithm was formulated to predict respiratory failure. RESULTS Respiratory failure developed in 140 of the 1032 patients in the study cohort. Patients with respiratory failure were older; had a higher mean Injury Severity Score (ISS) and Charlson Comorbidity Index Score; had greater incidences of pneumothorax, pulmonary contusion, and thoracic level injury; had a lower mean Glasgow Coma Score (GCS); were more likely to have had a posterior surgical approach; and had a longer mean time from admission to surgical stabilization than the patients without respiratory failure (p < 0.05). Multivariate analysis identified five independent risk factors for respiratory failure: an age of more than thirty-five years, an ISS of > 25 points, a GCS of < or = 12 points, blunt chest injury, and surgical stabilization performed more than two days after admission. An algorithm was created to determine, on the basis of the number of preoperative predictors present, the relative risk of respiratory failure when surgery was delayed for more than two days. CONCLUSIONS Independent risk factors for respiratory failure were identified in an analysis of a large cohort of patients who had undergone operative stabilization of thoracic and lumbar spine fractures. Early operative stabilization of these fractures, the only risk factor that can be controlled by the physician, may decrease the risk of respiratory failure in multiply injured patients.

Inter- and intraobserver reliability of computed tomography in assessment of thoracic pedicle screw placement

Study Design. Reliability study of computed tomography imaging in 12 cadaver specimens instrumented with titanium or stainless steel thoracic pedicle screws. Objective. To evaluate inter- and intraobserver reliability of computed tomography scan in determining the accuracy of thoracic pedicle screw placement and to identify the differences in observers’ agreement when viewing stainless steel versus titanium screws. Summary of Background Data. Computed tomography is often used to assess the accuracy of pedicle screw placement. Accuracy of screw placement is important in the thoracic spine where pedicle morphometry increases the difficulty of screw placement (vital structures are at increased risk). The current literature lacks a critical evaluation of computed tomography reliability among observers. Methods. Twelve adult cadavers were instrumented with thoracic pedicle screws. Nine cadavers were instrumented with titanium screws and three with stainless steel screws. The spines were imaged with computed tomography. Three observers used a grading scale to score the extent of pedicle violation and independently scored the placement of each pedicle screw on three separate occasions. Interobserver and intraobserver agreement were determined by using the kappa statistic. Results. The mean kappa score for interobserver agreement for all 12 specimens (including titanium and stainless steel screws) was 0.51, which correlates with a moderate degree of agreement. Although the interobserver kappa statistics for titanium (&kgr; = 0.53) and stainless screws (&kgr; = 0.44) showed a moderate degree of agreement, the intraobserver reliability was substantial (&kgr; = 0.63). The mean intraobserver kappa for titanium screws was 0.63 and for stainless steel screws was 0.62. Conclusions. Our data show that interobserver agreement is moderate and intraobserver agreement is substantial when computed tomography is used to assess placement of thoracic pedicle screws. We conclude that computed tomography is reliable for evaluating thoracic pedicle screw placement throughout the thoracic spine.

Magnetic Resonance Neurography for Cervical Radiculopathy: A Preliminary Report

Magnetic resonance neurography was used to directly image cervical spinal nerves in patients with clinical and radiographic evidence of cervical radiculopathy. A magnetic resonance imaging phased-array coil system was used to obtain high-resolution coronal T1-weighted spin echo, coronal/axial T2-weighted fast spin echo with fat saturation, and coronal/axial fast short tau inversion recovery weighted images of the cervical spine and spinal nerves. Three patients with neck and upper extremity pain and one asymptomatic volunteer were studied. The T2-weighted and the fast short tau inversion recovery images demonstrated markedly increased signal in the proximal portion of the affected spinal nerves. In two patients, contrast-to-noise measurements of the affected spinal nerves showed a markedly increased intensity compared with that of the noninvolved spinal nerves. Our findings demonstrate that phased-array coils used in conjunction with magnetic resonance neurography sequences can detect signal abnormalities within compressed cervical spinal nerves in patients with corresponding radicular symptoms and findings. This technique may prove to be helpful in evaluating patients with multilevel disc and/or spondylotic disease of the cervical spine.

Paragangliomas of the sellar region: Report of two cases

Two cases of paraganglioma arising from the parasellar region are presented. Both occurred in middle-aged women who sought treatment of headaches but who had no endocrinological dysfunction; one case was associated with ophthalmoplegia from cavernous sinus involvement. Diagnosis in both cases was confirmed by typical histological appearance and cytochemical demonstration of immunoreactive chromogranin in tumor cells. The pathological features and possible pathogenesis of parasellar paragangliomas are discussed.

Paragangliomas of the Sellar Region

Two cases of paraganglioma arising from the parasellar region are presented. Both occurred in middle-aged women who sought treatment of headaches but who had no endocrinological dysfunction; one case was associated with ophthalmoplegia from cavernous sinus involvement. Diagnosis in both cases was confirmed by typical histological appearance and cytochemical demonstration of immunoreactive chromogranin in tumor cells. The pathological features and possible pathogenesis of parasellar paragangliomas are discussed.

Blocking of up-regulated ICAM-1 does not prevent macrophage infiltration during Wallerian degeneration of peripheral nerve.

Circulating blood monocytes infiltrate into distal degenerating nerve and differentiate into activated macrophages that remove degenerating axonal and myelin debris and promote axonal regeneration. The cellular and molecular mechanisms responsible for this monocyte-macrophage recruitment remain largely unknown. Cell adhesion molecules which mediate monocyte and endothelial cell interactions, such as the endothelial cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) interaction with the monocyte adhesion molecules Mac-1 (complement receptor type 3) and LFA-1 (lymphocyte function-associated antigen-1), have been shown to play a critical role in mediating the transendothelial migration of circulating monocytes into nonneural tissues following various types of injury. This study investigated whether these cell adhesion molecules also play a critical role in mediating monocyte-macrophage infiltration during Wallerian degeneration of peripheral nerve. Following sciatic nerve transection, Mac-1- and LFA-1-positive macrophages in distal degenerating nerve increased in number at 2 days and peaked at 14 days before declining. The number of ICAM-1-immunostained blood vessels increased maximally at 1 day before declining to baseline levels by 14 days. Three days following nerve transection, the intensity of ICAM-1 immunostaining on intraneural blood vessels was maximal and then decreased to baseline levels by 14 days. To test the role of ICAM-1 in mediating monocyte-macrophage recruitment, we used two complementary experimental strategies following a sciatic nerve transection: (1) intravenous administration of a rat ICAM-1-blocking monoclonal antibody and (2) ICAM-1 knockout mice. In both cases, the number of infiltrating monocytes-macrophages was above controls, which is opposite to what has been shown to occur in other tissues following injury.

Resolution of an actinomycotic abscess with nonsurgical treatment: case report.

A case of actinomycotic brain abscess is presented. Conservative treatment by prolonged administration of antibiotics after needle biopsy showed complete resolution of the abscess. Previously reported cases suggest that definitive treatment requires excision or open surgical drainage of the abscess. The case presented suggests an alternative approach to treating this unusual cause of brain abscess.

Sacral screw fixation

Because of the difficulty in obtaining a fusion across the lumbosacral junction, special consideration must be given to obtain adequate sacral fixation. Options include anteromedial (pedicle) or anterolateral (alar) screws at the S1. Alternatively, screws can be placed in the S2 region, although these screws are only viewed as adjuncts to other points of sacral fixation. Bone quality, purchase of cortical bone, and screw length all influence the strength of a construct, with bicortical purchase in the S1 pedicle identified as the best option in multiple load-to-failure tests. Surgeons must remember, however, that the added fixation afforded with bicortical placement of screws must be balanced with the added risk of neurovascular injury.