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Giovanni La Rosa, Domenico d'Avella, Alfredo Conti, Salvatore Cardali, Domenico La Torre, Fabio Cacciola, Marcello Longo and Francesco Tomasello

Spinal epidural hematomas (SEHs) are uncommon complications caused by traumatic injuries to the spine. Emergency surgical evacuation is the standard treatment. Although recognized in the literature, the possibility of nonsurgical treatment of traumatic SEHs is far from being codified. The authors report on the treatment of four patients whose traumatic SEHs were diagnosed by magnetic resonance (MRI) imaging and managed conservatively with excellent results.

All patients had suffered severe spine injury with fracture of a lumbar vertebral body, were admitted within 12 hours of trauma, and exhibited only minimal neurological disturbances on admission. Magnetic resonance imaging studies were performed within 24 hours of trauma. Hematomas appeared isointense/slightly hyperintense on T1- and heterogeneous on T2-weighted MR images. Clot thickness varied between 0.8 cm and 1 cm, width between 1 cm and 1.8 cm, and length between 2.7 and 9 cm. In light of each patient's fairly good neurological condition a conservative approach was taken. In all cases serial MR imaging documented progressive clot resolution, which was completed within 8 to 10 days of trauma. At discharge all patients were neurologically intact.

The conservative treatment option of traumatic SEH should be reserved for exceptional cases whose deficits are minimal, when neurological deterioration is followed by early and sustained spontaneous recovery, and when there are clear medical contraindications for surgery. The results of the present study confirm that nonsurgical treatment is feasible in a subgroup of minimally symptomatic patients who harbor moderate-sized SEHs. Although the authors' experience shows a good spontaneous outcome of some traumatic SEH, further studies are necessary to understand the real spectrum of nonsurgical treatment of such lesions.

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Giovanni La Rosa, Domenico d'Avella, Alfredo Conti, Salvatore Cardali, Domenico La Torre, Fabio Cacciola, Marcello Longo and Francesco Tomasello

✓ Spinal epidural hematomas (SEHs) are uncommon complications of traumatic injury to the spine. Emergency surgical evacuation is the standard treatment. Although it is recognized in the literature, the possibility of nonsurgical treatment of traumatic SEH is far from being codified. The authors report excellent outcomes in four conservatively managed patients who had sustained a severe spine injury with fracture of the lumbar vertebral body and in whom traumatic SEHs were diagnosed by magnetic resonance imaging. Although in the authors' experience a good spontaneous outcome in this subgroup of minimally symptomatic patients harboring moderate-sized SEHs has been achieved, further studies are necessary to understand the real spectrum of nonsurgical treatment of such lesions.

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Giovanni La Rosa, Antonino Germanò, Alfredo Conti, Fabio Cacciola, Gerardo Caruso and Francesco Tomasello

Surgery for adult patients with lumbar and lumbosacral spondylolisthesis is reserved for those with intractable radiculopathy, claudication, or symptomatic spinal instability. Internal fixation, in which posterior fusion, transpedicular screw fixation, and implantation of titanium devices are performed, has been advocated to improve fusion rates and clinical results. Fourteen consecutive patients with Grade II to III lumbar and lumbosacral spondylolisthesis who underwent posterior decompression, reduction, autologous posterior facet joint arthrodesis, and SOCON-SRI implantation are retrospectively reviewed.

All patients underwent complete preoperative clinical and neuroradiological evaluation. Treatment consisted of posterior decompressive surgery and implantation of the SOCON-SRI system (transpedicular screws, prebent longitudinal rods, and one locking-screw clamps). Distraction of the interbody space and rotation were performed to achieve an optimum spinal realignment. The facet joints were fused by using autologous bone graft. The authors obtained detailed clinical, functional, economic, and neuroradiological follow-up data for up to 14 months (range 8–18 months).

The efficacy of the treatment was evaluated by comparing pre- and postoperative data. Pain was decreased in all cases, neurological dysfunction ameliorated in 50%, and functional and economic status was improved in 78% and 100%, respectively. No cases of fusion failure or instrumentation-related complications occurred. The authors describe their results of treating patients with spondylolisthesis in the light of the rationale for surgery and the more recent pertinent literature.

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Domenico Gerardo Iacopino, Maria Giusa, Alfredo Conti, Salvatore Cardali and Francesco Tomasello

The authors describe a case of spinal arteriovenous fistula (AVF) treated by a microvauscular Doppler–assisted surgical interruption of the arterialized vein. Microvascular Doppler monitoring represents a valid, widely available, non-invasive tool that enables identification, through flow spectrum analysis, of components of this type of vascular malformation. In this case because the location of the fistula was identified prior to opening the dura only minimally invasive surgery was required. Direct recordings of the arterialized draining vein and the nidus of the fistula demonstrated a pathological spectrum caused by the arterial supply and the disturbed venous outflow in which a high-resistance flow pattern and low diastolic flow resembling an arterial-like flow velocity were observed. The fistula was obliterated by interruption of the draining vein, and Doppler measurements provided information on flow velocity changes in the medullary veins from an arterial to a venous pattern. The absence of any residual flow in the AVF confirmed successful hemodynamic treatment.

Intraoperative microvascular Doppler recording during surgical closure of spinal AVF is a widely available and reliable monitoring modality that helps to produce excellent clinical results.

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Giovanni La Rosa, Fabio Cacciola, Alfredo Conti, Salvatore Cardali, Domenico La Torre, Nicola Maria Gambadauro and Francesco Tomasello

Object

Clinical and radiographic results in 30 consecutive patients who underwent posterior lumbar fixation and posterior facet joint or posterior interbody fusion for Meyerding Grade II/III spondylolisthesis were assessed: 1) to address the suitability of a dynamic stabilization; and 2) to investigate whether there are differences in terms of clinical and functional results and biomechanical properties between these two types of arthrodesis.

Methods

Between June 1998 and April 2000, 16 patients underwent posterior interfacet fusion and implantation of the SOCON-SRI system. In 14 patients posterior lumbar interbody fusion (PLIF) and placement of the same system were performed. Clinical, economic, functional, and radiographic data were recorded pre- and postoperatively.

The average changes in the Prolo Scale economic and functional scores were 1.25 and 1.62, respectively, in patients who underwent posterior fusion; the average measured preoperative vertebral slippage was 47.8% (range 30–65%), and postoperatively it was 18.5% (range 15–25%). In patients in whom PLIF was performed, the average changes in economic and functional score were 1.21 and 1.36, respectively, and the average preoperative vertebral slippage was 43.5% (range 30–55%) compared with 20% (range 15–25%) postoperatively.

Conclusions

The use of a segmental pedicle screw fixation with the SOCON-SRI system successfully combines the goal of solid fusion with the requirements of nerve root decompression. When the two fusion techniques were compared, an overall superior reliability and resistance of the systems was associated with the PLIF procedure (p = 0.04) but clinical outcomes did not differ greatly (p ≥ 0.05).

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Giovanni Grasso, Marcello Passalacqua, Alessandra Sfacteria, Alfredo Conti, Antonio Morabito, Giuseppe Mazzullo, Gionata De Vico, Michele Buemi, Battesimo Macrì and Francesco Tomasello

Object. Results of recent studies indicate that erythropoietin (EPO) produces a neuroprotective effect on experimental subarachnoid hemorrhage (SAH). It has been reported that S-100 protein levels increase in cerebrospinal fluid (CSF) after SAH, providing a highly prognostic indication of unfavorable outcome. This study was conducted to validate further the findings of S-100 protein as an index of brain damage and to assess whether treatment with recombinant human EPO (rhEPO) would limit the increase of S-100 protein level in CSF following experimental SAH.

Methods. Thirty-two rabbits were each assigned to one of four groups: Group 1, control; Group 2, SAH; Group 3, SAH plus placebo; and Group 4, SAH plus rhEPO (each group consisted of eight rabbits). The rhEPO and placebo were administered to the rabbits after SAH had been induced, and S-100 protein levels in the CSF of these animals were measured at 24, 48, and 72 hours after the experimental procedure. In each group of animals levels of S-100 protein were compared with the mortality rate, neurological outcome, and neuronal ischemic damage. High S-100 protein levels were found in rabbits in Groups 2 and 3, which exhibited poor neurological status and harbored a high number of damaged cortical neurons. Favorable neurological outcome and significant reductions in total numbers of damaged neurons were observed in animals in Group 4 in which there were significantly lower S-100 protein concentrations compared with animals in Groups 2 and 3 (p < 0.001).

Conclusions. The results of this study support the concept that determination of the S-100 protein level in CSF has prognostic value after SAH. The findings also confirm that rhEPO acts as a neuroprotective agent during experimental SAH.

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Domenico G. Iacopino, Alfredo Conti, Calogero Battaglia, Clotilde Siliotti, Tullio Lucanto, Letterio B. Santamaria and Francesco Tomasello

Object. Nitrous oxide has an adverse effect on cerebrovascular hemodynamics. Increased intracranial pressure, cerebral blood flow (CBF), cerebral metabolic rate of O2 (CMRO2), and reduced autoregulation indices have been reported, but their magnitudes are still being debated.

This study was designed to evaluate the effect of N2O on CBF and autoregulatory indexes during N2O—sevoflurane anesthesia in a prospective randomized controlled series of patients.

Methods. Two groups of 20 patients were studied on the basis of the use of N2O in the anesthetic gas mixture. The transient hyperemic response test, which relies on transcranial Doppler ultrasound techniques, was used to assess cerebral hemodynamics.

The time-averaged mean flow velocity, considered to be an index of actual CBF, increased significantly (p < 0.001) after introduction of N2O. The hyperemic response, considered as the index of autoregulatory potential, decreased significantly after introduction of N2O into the gas mixture (p < 0.001).

Conclusions. The increase in CBF and the reduction in autoregulatory indices suggest caution in using N2O during sevoflurane anesthesia, especially in patients with reduced autoregulatory reserve and during neurosurgical interventions. Transcranial Doppler ultrasonography is an efficacious method to evaluate the effects of anesthetic agents on CBF.

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Giovanni La Rosa, Alfredo Conti, Fabio Cacciola, Salvatore Cardali, Domenico La Torre, Nicola Maria Gambadauro and Francesco Tomasello

Object. Posterolateral fusion involving instrumentation-assisted segmental fixation represents a valid procedure in the treatment of lumbar instability. In cases of anterior column failure, such as in isthmic spondylolisthesis, supplemental posterior lumbar interbody fusion (PLIF) may improve the fusion rate and endurance of the construct. Posterior lumbar interbody fusion is, however, a more demanding procedure and increases costs and risks of the intervention. The advantages of this technique must, therefore, be weighed against those of a simple posterior lumbar fusion.

Methods. Thirty-five consecutive patients underwent pedicle screw fixation for isthmic spondylolisthesis. In 18 patients posterior lumbar fusion was performed, and in 17 patients PLIF was added. Clinical, economic, functional, and radiographic data were assessed to determine differences in clinical and functional results and biomechanical properties.

At 2-year follow-up examination, the correction of subluxation, disc height, and foraminal area were maintained in the group in which a PLIF procedure was performed, but not in the posterolateral fusion—only group (p < 0.05). Nevertheless, no statistical intergroup differences were demonstrated in terms of neurological improvement (p = 1), economic (p = 0.43), or functional (p = 0.95) outcome, nor in terms of fusion rate (p = 0.49).

Conclusions. The authors' findings support the view that an interbody fusion confers superior mechanical strength to the spinal construct; when posterolateral fusion is the sole intervention, progressive loss of the extreme correction can be expected. Such mechanical insufficiency, however, did not influence clinical outcome.

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Giovanni La Rosa, Salvatore Cardali, Tiziana Genovese, Alfredo Conti, Rosanna Di Paola, Domenico La Torre, Fabio Cacciola and Salvatore Cuzzocrea

Object. The nuclear factor—κB (NF-κB) is a transcription factor that plays a pivotal role in the induction of genes involved in physiological processes and in the response to inflammation. The authors of recent studies have demonstrated that NF-κB and oxidative stress contribute to secondary injury after impact-induced spinal cord injury (SCI) in the rat. Dithiocarbamates are antioxidants that are potent inhibitors of NF-κB. The authors postulated that pyrrolidine dithiocarbamate (PDTC) would attenuate NF-κB—related inflammatory and oxidative events that occur after SCI.

Methods. Spinal cord injury was induced by the application of vascular clips (force of 50 g) to the dura mater after a four-level T5–8 laminectomy. The authors investigated the effects of PDTC (30 mg/kg administered 30 minutes before SCI and 6 hours after SCI) on the development of the inflammatory response associated with SCI in rats. Levels of myeloperoxidase activity were measured as an indicator of polymorphonuclear infiltration; malondialdehyde levels in the spinal cord tissue were determined as an indicator of lipid peroxidation. The following studies were performed: immunohistochemical analysis to assess levels of inducible nitric oxide synthase (iNOS), nitrotyrosine formation, poly([adenosine diphosphate]-ribose) polymerase (PARP) activity; Western blot analysis to determine cytoplasmic levels of inhibitory—κB-α (IκB-α); and electrophoretic mobility-shift assay to measure the level of DNA/NF-κB binding.

The PDTC treatment exerted potent antiinflammatory effects with significant reduction of polymorphonuclear cell infiltration, lipid peroxidation, and iNOS activity. Furthermore, administration of PDTC reduced immunohistochemical evidence of formation of nitrotyrosine and PARP activation in the spinal cord section obtained in the SCI-treated rats. Additionally, PDTC treatment significantly prevented the activation of NF-κB (electrophoretic mobility-shift assay and immunoblot analysis).

Conclusions. Overall, the results clearly demonstrate that PDTC-related prevention of the activation of NF-κB reduces the development of some secondary injury events after SCI. Therefore, inhibition of NF-κB may represent a novel approach in the treatment of SCIs.

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Alfredo Conti, M'Hammed Aguennouz, Domenico La Torre, Salvatore Cardali, Filippo Flavio Angileri, Catia Buemi, Chiara Tomasello, Domenico Gerardo Iacopino, Domenico D'Avella, Giuseppe Vita and Francesco Tomasello

Object. Tumor necrosis factor receptor (TNFR)—associated factors (TRAFs) are a recently established group of proteins involved in the intracellular signaling of the TNFR superfamily members. The TRAFs have been implicated in promoting cell survival through the activation of transcription factor nuclear factor (NF)—κB. The authors investigated the expression of NF-κB, caspase 3, TRAF1, TRAF2, and TRAF-associated NF-κB activator/TRAF—interacting protein (TANK/I-TRAF), a regulator of TRAF activity, in human gliomas.

Methods. Tumor samples were obtained in 27 adult patients harboring seven low-grade gliomas, nine anaplastic astrocytomas, and 11 glioblastomas multiforme. The NF-κB activation was analyzed using the electrophoresis mobility shift assay; TRAF1, TRAF2, TANK/I-TRAF, and caspase 3 expression were studied using Western blot analysis.

Upregulated NF-κB DNA—binding activity, compared with that in normal brain tissue, was detected in all tumor samples (p = 0.002). The level of NF-κB activity showed some correlation with World Health Organization tumor grades (p = 0.01), even though variable activity levels were demonstrated in relation to tissue heterogeneity, which resulted in a substantial number of outliers in the quantitative analysis. Increased levels of TRAF1, TRAF2, and TANK/I-TRAF were expressed in astrocytomas compared with levels in normal brain tissue (p = 0.02, 0.006, and 0.01, respectively).

Conclusions. Data in this study confirm the upregulation of NF-κB in gliomas and reveal a correlation between levels of this transcription factor and tumor grade. A constitutive expression of TRAF1, TRAF2, and TANK/I-TRAF in human gliomas was documented. These proteins are involved in the intracellular signal transduction of the TNFR superfamily and in the control of NF-κB expression and its antiapoptotic activity.