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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, 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, 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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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, 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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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.

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Giovanni Grasso, Alessandra Sfacteria, Serhat Erbayraktar, Marcello Passalacqua, Francesco Meli, Necati Gokmen, Osman Yilmaz, Domenico La Torre, Michele Buemi, Domenico G. Iacopino, Thomas Coleman, Anthony Cerami, Michael Brines, and Francesco Tomasello

Object

Spinal cord injury (SCI) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its nonerythropoietic derivatives asialoEPO and carbamylated EPO have markedly improved functional outcome when administered after compressive SCI. However, an optimum treatment paradigm is currently unknown. Because the uninjured spinal cord expresses a high density of EPO receptor (EPOR) in the basal state, signaling through these existing receptors in advance of injury (pharmacological preconditioning) might confer neuroprotection and therefore be potentially useful in situations of anticipated damage.

Methods

The authors compared asialoEPO, a molecule that binds to the EPOR with high affinity but with a brief serum half-life (t1/2 < 2 minutes), to EPO to determine whether a single dose (10 μg/kg of body weight) administered by intravenous injection 24 hours before 1 minute of spinal cord compression provides benefit as determined by a 6-week assessment of neurological outcome and by histopathological analysis. Rats pretreated with asialoEPO or EPO and then subjected to a compressive injury exhibited improved motor function over 42 days, compared with animals treated with saline solution. However, pretreatment efficacy was substantially poorer than efficacy of treatment initiated at the time of injury. Serum samples drawn immediately before compression confirmed that no detectable asialoEPO remained within the systemic circulation. Western blot and immunohistochemical analyses performed using uninjured spinal cord 24 hours after a dose of asialoEPO exhibited a marked increase in glial fibrillary acidic protein, suggesting a glial response to EPO administration.

Conclusions

These results demonstrate that EPO and its analog do not need to be present at the time of injury to provide tissue protection and that tissue protection is markedly effective when either agent is administered immediately after injury. Furthermore, the findings suggest that asialoEPO is a useful reagent with which to study the dynamics of EPO-mediated neuroprotection. In addition, the findings support the concept of using a nonerythropoietic EPO derivative to provide tissue protection without activating the undesirable effects of EPO.

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Alfredo Conti, Antonio Pontoriero, Ignazio Salamone, Carmelo Siragusa, Federica Midili, Domenico La Torre, Amedeo Calisto, Francesca Granata, Pantaleo Romanelli, Costantino De Renzis, and Francesco Tomasello

Symptomatic edema is a potential complication of meningioma radiosurgery. Parasagittal meningiomas are at a particular risk for symptomatic edema, suggesting a role for a venous occlusive complication. The authors sought to develop a strategy to optimize CyberKnife stereotactic radiosurgical treatment parameters to reduce the irradiation of the peritumoral venous system. Multislice CT venography with 3D reconstructions was performed and coregistered with thin-section, contrast-enhanced, volumetric MR images. The tumor and critical volumes were contoured on the MR images. Venous anatomical details obtained from the CT venographic study were then exported onto the MR imaging and fused MR imaging-CT study. Target and critical structure volumes and dosimetric parameters obtained with this method were analyzed. The authors found that reducing the irradiation of veins that course along the surface of the meningioma, which may be at risk for radiation-induced occlusion, is feasible in parasagittal meningioma radiosurgery without compromising other treatment parameters including conformality, homogeneity, and target coverage. Long-term follow-up is needed to assess the clinical validity of this treatment strategy.