Selection of surgical treatment approaches for cervicothoracic spinal tuberculosis: A 10-year case review

<div><p>Background</p><p>Cervicothoracic spinal tuberculosis is a rare disease. Due to its difficult and challenging surgical exposure, its surgical treatment approach remains inconclusive. Long-term follow-up studies to address this puzzling issue are rarely seen in the literature. The purpose of this study was to explore the selection of surgical treatment approaches for cervicothoracic spinal tuberculosis through a 10-year case review.</p><p>Methods</p><p>From January 2003 to January 2013, 45 patients suffering from cervicothoracic spinal tuberculosis were treated surgically. According to the relation between the tuberculosis lesion segments and the suprasternal notch on sagittal MRI, 19 patients were treated with a single-stage anterior debridement, fusion and instrumentation approach, and the other 26 patients were treated with a single-stage anterior debridement and fusion, posterior fusion and instrumentation approach. The clinical efficacy was evaluated using statistical analysis based on the Cobb angle of kyphosis, the Neck Disability Index (NDI) and the Japanese Orthopedic Association (JOA) scoring system. The neurofunctional recovery was assessed by the American Spinal Injury Association (ASIA) system.</p><p>Results</p><p>All patients were followed up for 6.6 years on average (range 3–13 years). No instrumentation loosening, migration or breakage was observed during the follow-up. The kyphosis angle and NDI and JOA scores were significantly changed from preoperative values of 34.7±6.8°, 39.6±4.6 and 10.7±2.8 to postoperative values of 10.2±2.4°, 11.4±3.6 and 17.6±2.4, respectively (p<0.05). Aside from one recurrent patient, bone fusion was achieved in the other 44 patients within 6 to 9 months (mean 7.2 months). No severe postoperative complications occurred, and patients’ neurologic function was improved in various degrees.</p><p>Conclusions</p><p>In the surgical treatment of cervicothoracic spinal tuberculosis, single-stage cervical anterior approach with or without partial manubriotomy is capable of complete debridement for tuberculosis lesions. The manner of fixation should be selected based on the anatomical relation of the suprasternal notch and the diseased segments as revealed on sagittal MRI images.</p></div

Effects of PQQ on LPS-induced p65 and NF-κB activity in microglial cells.

<p>(A) Representative images of NF-κB p65 in microglial cells of each group. Cells were pretreated with or without PQQ for 1 h followed by 100 ng/ml LPS treatment for 2 h. Microglial cells were incubated with NF-κB p65 antibody and immunofluorescence microscopy was used to visualize the localization of NF-κB p65 (Green; a-c), boxed regions in (a-c) are also shown at×200 (j-m). Nuclei were visualized using DAPI counterstaining (Blue; d-f). (B) Cells were treated with 100 ng/m LPS for indicated time. p65 protein level was measured by western blot analysis. Non-phosphorylated p65 was used as loading control, and the expression of p-p65 was normalized to control and quantified by densitometric analysis. The results shown are mean ± S.E.M. of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p

Classification of patients.

<p>Group A: the tuberculosis focus was located higher than the suprasternal notch level. Group B: the tuberculosis focus lay exactly on the suprasternal notch level. Group C: the tuberculosis focus was located lower than the suprasternal notch level. D: diseased segments. M: manubrium. Arrow: the suprasternal notch level.</p

Another typical case for group A.

<p>A 45-years-old patient’s preoperative CT scanning shows destructive segments located at C7/T1 segments with collapse of T1 vertebra (a-b). Preoperative sagittal MRI shows the tuberculosis focus is located higher than the suprasternal notch level (c). One-week postoperative X-ray image shows internal fixation in good position (d). Three years postoperative CT scanning reveals cervicothoracic anterior graft fusion (e-f).</p

Statistical results in the kyphosis Cobb angle, NDI score and JOA score.

<p>Statistical results in the kyphosis Cobb angle, NDI score and JOA score.</p

Effect of PQQ on Microglia Activation in the Brain.

<p>Representative photographs show Iba-1 immuno-stained microglia of the mouse brain (A). LPS group shows mostly an activated-form of microglia which display an increased size, irregular shape, thickened and shortened processes and intensified Iba-1 immunostaining density, in the dentate gyrus of hippocampus (DG) and cerebral cortex (Cortex) compared to the normal group. Moreover, both PQQ treated groups show a decrease of morphological activation of microglia in all brain regions with respect to LPS group. Representative DG (a–d) and Cortex (e–h) immunostained slices are presented at ×40. High power images of Iba-1-expressed microglia in the boxed regions in (f), (g) and (h) are also shown at×200 (i–l). Arrow indicates the Iba-1-expressed microglia. The number of microglia was counted and normalized in the corresponding same area (B). LPS increases the number of Iba-1-expressed microglia in the brain. PQQ treatment significantly reduces the number of Iba-1-expressed microglia both in the cerebral cortex and DG. The results shown are mean ± S.E.M. (<i>n</i> = 6 in each group) of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p

A typical case for group B and C.

<p>A 27-year-old patient’s preoperative CT scanning shows destructive segments located at the T2/3 segments (a-b). Preoperative MRI shows a huge paravertebral abscess located in front of the vertebral bodies and the compression of the spinal cord, while the tuberculosis focus lies exactly on the suprasternal notch level (c-d). Two-week postoperative antero-posterior and lateral plain radiograph shows the internal instruments in a satisfactory position (e-f). Four-year postoperative CT scanning demonstrates that the cervicothoracic fusion is consolidated completely (g). Six-year postoperative lateral plain radiograph shows no instrumentation loosening, migration or breakage (h).</p

Effects of PQQ on LPS-stimulated expression of pro-inflammatory mediators in microglial cells.

<p>Cells were treated with the indicated concentrations of PQQ 1 h prior to 6 h co-treatment of LPS (100 ng/ml). Primary microglia were harvested and total RNA was prepared. The mRNA expression of pro-inflammatory mediators: TNF-a, IL-1β, IL-6, COX-2, MCP-1 and MIP-1α was measured by real-time PCR. GAPDH was used as an internal control. The results shown are mean ± S.E.M. of three independent experiments. <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p

Effects of PQQ on LPS-induced NO, PGE2 production and iNOS, COX-2 expression in microglia cells.

<p>Primary microglia were pretreated with or without PQQ for 1 h followed by LPS (100 ng/ml) treatment for indicated durations. Culture supernatants were collected 24 h later, the released NO in primary microglia (A) was determined by the Griess assay, total mRNA was harvested 6 h later, and the mRNA level of iNOS (B) and COX-2 (D) was measured by real-time PCR. (C) Concentrations of PGE2 in the culture supernatants of primary microglia were determined by ELISA. (E) 24 h later, the protein level of iNOS and COX-2 were detected by western blot analysis in primary microglia cells. The results presented as mean ± S.E.M. of at least three independent experiments, <i>*p<0.05 vs. control group, #p<0.05 vs. only LPS group.</i></p

Demographic and clinical characteristics of the patients.

<p>Demographic and clinical characteristics of the patients.</p