Kia Rezajooi

NG2 proteoglycan expression in the peripheral nervous system: upregulation following injury and comparison with CNS lesions

The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and thus may be able to inhibit axonal regeneration in the CNS. We have used immunohistochemistry to compare the expression of NG2 in the PNS, where axons regenerate, and the spinal cord, where regeneration fails. NG2 is expressed by satellite cells in dorsal root ganglia (DRG) and in the perineurium and endoneurium of intact sciatic nerves of adult rats. Endoneurial NG2-positive cells were S100-negative. Injury to dorsal roots, ventral rami or sciatic nerves had no effect on NG2 expression in DRG but sciatic nerve section or crush caused an upregulation of NG2 in the damaged nerve. Strongly NG2-positive cells in damaged nerves were S100-negative. The proximal stump of severed nerves was capped by dense NG2, which surrounded bundles of regenerating axons. The distal stump, into which axons regenerated, also contained many NG2-positive/S100-negative cells. Immunoelectron microscopy revealed that most NG2-positive cells in distal stumps had perineurial or fibroblast-like morphologies, with NG2 being concentrated at the poles of the cells in regions exhibiting microvillus-like protrusions or caveolae. Compression and partial transection injuries to the spinal cord also caused an upregulation of NG2, and NG2-positive cells and processes invaded the lesion sites. Transganglionically labelled ascending dorsal column fibres, stimulated to sprout by a conditioning sciatic nerve injury, ended in the borders of lesions among many NG2-positive processes. Thus, NG2 upregulation is a feature of the response to injury in peripheral nerves and in the spinal cord, but it does not appear to limit regeneration in the sciatic nerve.

Peritumoral edema and prognosis in intracranial meningioma surgery

Peritumoral brain edema (PTBE) is often associated with meningiomas. PTBE is probably implicated in the complications occurring in intracranial meningiomas. The goal of this study was to determine the exact implication of PTBE in prognosis. Thirty consecutive patients who underwent surgery for intracranial meningiomas were investigated over a 1-year period. We focused on the clinical and radiological status before and after surgery, and postoperative complications. Multiple regression analysis revealed a close correlation (p<0.05) between PTBE and symptoms, type of arterial supply, difficulty of surgical removal, and postoperative complications. PTBE is likely implicated in the morbidity of intracranial meningiomas. We suggest predictive factors for difficult surgical resection, and emphasise the importance of medical preoperative management and post-operative follow-up.

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse

BackgroundThe chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve.ResultsWe studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST) axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC) axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion), most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice.Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG) cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses revealed significant differences between wild-type and knockout mice.ConclusionThese findings show that NG2 is unlikely to be a major inhibitor of axonal regeneration after injury to the CNS, and, further, that NG2 is unlikely to be necessary for regeneration or functional recovery following peripheral nerve injury.

Financial and clinical governance implications of clinical coding accuracy in neurosurgery: A multidisciplinary audit

Clinical coding is the translation of documented clinical activities during an admission to a codified language. Healthcare Resource Groupings (HRGs) are derived from coding data and are used to calculate payment to hospitals in England, Wales and Scotland and to conduct national audit and benchmarking exercises. Coding is an error-prone process and an understanding of its accuracy within neurosurgery is critical for financial, organizational and clinical governance purposes. We undertook a multidisciplinary audit of neurosurgical clinical coding accuracy. Neurosurgeons trained in coding assessed the accuracy of 386 patient episodes. Where clinicians felt a coding error was present, the case was discussed with an experienced clinical coder. Concordance between the initial coder-only clinical coding and the final clinician-coder multidisciplinary coding was assessed. At least one coding error occurred in 71/386 patients (18.4%). There were 36 diagnosis and 93 procedure errors and in 40 cases, the initial HRG changed (10.4%). Financially, this translated to £111 revenue-loss per patient episode and projected to £171,452 of annual loss to the department. 85% of all coding errors were due to accumulation of coding changes that occurred only once in the whole data set. Neurosurgical clinical coding is error-prone. This is financially disadvantageous and with the coding data being the source of comparisons within and between departments, coding inaccuracies paint a distorted picture of departmental activity and subspecialism in audit and benchmarking. Clinical engagement improves accuracy and is encouraged within a clinical governance framework.

Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

BackgroundInflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation.ResultsApplication of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site.ConclusionInflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.

Anterior cervical corpectomy: review and comparison of results using titanium mesh cages and carbon fibre reinforced polymer cages.

Different types of cages have recently become available for reconstruction following anterior cervical corpectomy. We review the results using titanium mesh cages (TMC) and stackable CFRP (carbon fibre reinforced polymer) cages. Forty-two patients who underwent anterior cervical corpectomy between November 2001 and September 2008 were retrospectively reviewed. Pathologies included cervical spondylotic myelopathy (CSM), cervical radiculopathy, OPLL (ossified posterior longitudinal ligament), metastasis/primary bone tumour, rheumatoid arthritis and deformity correction. All patients were evaluated clinically and radiologically. Outcome was assessed on the basis of the Odoms criteria, neck disability index (NDI) and myelopathy disability index (MDI). Mean age was 60 years and mean follow-up was 1½ years. Majority of the patients had single-level corpectomy. Twenty-three patients had TMC cages while 19 patients had CFRP cages. The mean subsidence noted with TMC cage was 1.91 mm, while with the stackable CFRP cage it was 0.5 mm. This difference was statistically significant (p < 0.05). However, there was no statistically significant correlation noted between subsidence and clinical outcome (p > 0.05) or between subsidence and post-operative sagittal alignment (p > 0.05) in either of the groups. Three patients had significant subsidence (>3 mm), one of whom was symptomatic. There were no hardware-related complications. On the basis of the Odoms criterion, 9 patients (21.4%) had an excellent outcome, 14 patients (33.3%) had a good outcome, 9 patients (21.4%) had a fair outcome and 5 patients (11.9%) had a poor outcome, i.e. symptoms and signs unchanged or exacerbated. Mean post-operative NDI was 26.27% and mean post-operative MDI was 19.31%. Fusion was noted in all 42 cases. Both TMC and stackable CFRP cages provide solid anterior column reconstruction with good outcome following anterior cervical corpectomy. However, more subsidence is noted with TMC cages though this might not significantly alter the clinical outcome unless the subsidence is significant (>3 mm).

Lemierre’s syndrome: AN UNUSUAL MANIFESTATION OF SPINAL INFECTION

We report a case of Lemierres syndrome complicated by an epidural abscess. This manifestation of Lemierres syndrome has not been described previously.

Osteochondroma of C1 causing vertebral artery occlusion.

Abstract Spinal osteochondromas constitute a small percentage of all intraspinal tumours, and are a rare cause of neurological symptoms. We describe a patient with a vertebral artery occlusion secondary to an osteochondroma of the C1 vertebra presenting with symptoms of cerebral ischaemia. This case is reported because of its extreme rarity.

Malignant PEComa of the lumbar vertebra: a rare bone tumour

We describe the case of a 26-year-old patient with a perivascular epithelioid cell tumour (PEComa) involving the 5th lumbar vertebra. Radiological findings, pathological features and treatment are presented. We conclude that PEComas should be considered in the differential diagnosis of vertebral lesions.

Osteosarcoma of the spine: Dismal past, any hope for the future?

Abstract Purpose. The purpose of this study was to analyse all cases of spinal osteosarcoma (OS) treated in a regional bone tumour unit over the last 27 years. We were primarily interested in overall survival following tumour surgery, and if there is a difference in the survival of patients undergoing en bloc resection versus non-en bloc surgery. Methods. Prospectively maintained tumour databases were searched in a regional bone tumour unit. All cases of surgically managed spinal OS were extracted and inpatient notes, imaging (including staging), histological margin status, and outcomes (neurological deficit and survival curves) were reviewed. Results. Twenty-six patients were identified between 1985 and 2012. The median age was 26.5 years (range 6–78 y). Overall Kaplan–Meier survival was 69.5% (95% CI: 46.3–84.2%) and 10.8% (95% CI: 1.8–29.0%) at 1 and 5 years, respectively. There appears to be improved survival associated with primary spinal OS compared to that of metastatic disease, but this does not reach statistical significance (p = 0.29, Cox proportional hazards analysis). En bloc resection results in a significantly improved survival time compared to non-en bloc (biopsy and debulking): 44.1% alive at 2 years compared to 9.4%, respectively, p = 0.009. Conclusions. En bloc resection for primary spinal OS is associated with improved survival; there have been major changes in both surgical treatment and chemo/radiotherapy regimens over the period studied, potentially confounding the interpretation.