Fumito Tanabe

Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: Functional analysis of p62 and autophagy in hypoxic neuronal cells

Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3-II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic myelopathy patients.

Risk Factors for Venous Thromboembolism After Spine Surgery

AbstractThe efficacy and safety of chemical prophylaxis to prevent the development of deep venous thrombosis (DVT) or pulmonary embolism (PE) following spine surgery are controversial because of the possibility of epidural hematoma formation. Postoperative venous thromboembolism (VTE) after spine surgery occurs at a frequency similar to that seen after joint operations, so it is important to identify the risk factors for VTE formation following spine surgery. We therefore retrospectively studied data from patients who had undergone spinal surgery and developed postoperative VTE to identify those risk factors.We conducted a retrospective clinical study with logistic regression analysis of a group of 80 patients who had undergone spine surgery at our institution from June 2012 to August 2013. All patients had been screened by ultrasonography for DVT in the lower extremities. Parameters of the patients with VTE were compared with those without VTE using the Mann–Whitney U-test and Fisher exact probability test. Logistic regression analysis was used to analyze the risk factors associated with VTE. A value of P < 0.05 was used to denote statistical significance.The prevalence of VTE was 25.0% (20/80 patients). One patient had sensed some incongruity in the chest area, but the vital signs of all patients were stable. VTEs had developed in the pulmonary artery in one patient, in the superficial femoral vein in one patient, in the popliteal vein in two patients, and in the soleal vein in 18 patients. The Mann–Whitney U-test and Fisher exact probability test showed that, except for preoperative walking disability, none of the parameters showed a significant difference between patients with and without VTE. Risk factors identified in the multivariate logistic regression analysis were preoperative walking disability and age.The prevalence of VTE after spine surgery was relatively high. The most important risk factor for developing postoperative VTE was preoperative walking disability. Gait training during the early postoperative period is required to prevent VTE.

Risk factors for unavoidable removal of instrumentation after surgical site infection of spine surgery: A retrospective case-control study.

Abstract Surgical site infection (SSI) after spine instrumentation is difficult to treat, and often requires removal of instrumentation. The removal of instrumentation after spine surgery is a severe complication that can lead to the deterioration of activities of daily living and poor prognosis. Although there are many reports on SSI after spine surgery, few reports have investigated the risk factors for the removal of instrumentation after spine surgery SSI. This study aimed to identify the risk factors for unavoidable removal of instrumentation after SSI of spine surgery. We retrospectively reviewed 511 patients who underwent spine surgery with instrumentation at Kagoshima University Hospital from January 2006 to December 2014. Risk factors associated with SSI were analyzed via multiple logistic regression analysis. Parameters of the group that needed instrumentation removal were compared with the group that did not require instrumentation removal using the Mann–Whitney U and Fishers exact tests. The posterior approach was used in most cases (453 of 511 cases, 88.6%). SSI occurred in 16 of 511 cases (3.14%) of spine surgery with instrumentation. Multivariate logistic regression analysis identified 2 significant risk factors for SSI: operation time, and American Society of Anesthesiologists physical status classification ≥ 3. Twelve of the 16 patients with SSI (75%) were able to keep the instrumentation after SSI. Pseudarthrosis occurred in 2 of 4 cases (50%) after instrumentation removal. Risk factors identified for instrumentation removal after spine SSI were a greater number of past surgeries, low preoperative hemoglobin, high preoperative creatinine, high postoperative infection treatment score for the spine, and the presence of methicillin-resistant Staphylococcus aureus. In these high risk cases, attempts should be made to decrease the risk factors preoperatively, and careful postoperative monitoring should be conducted.

Retro-odontoid mass without atlantoaxial instability causing cervical myelopathy: a case report of transdural surgical resection

Introduction:Retro-odontoid mass rarely occur in patients with noninflammatory retro-odontoid lesions without atlantoaxial instability. We describe a rare case of retro-odontoid mass without atlantoaxial instability operated on by a transdural approach.Case Presentation:The patient was an 83-year-old man who presented with a retro-odontoid mass causing symptomatic cervical myelopathy. Preoperative magnetic resonance imaging (MRI) revealed that the mass was severely compressing the spinal cord. We operated on it via a C1 laminectomy and performed tumor resection by a transdural approach. Pathological findings from the operative specimen confirmed the diagnosis; histopathological examination revealed that the mass contained fibrinoid material, and collagenous tissue with myxoid changes, but no granulation or a granulomatous lesion. Postoperative MRI confirmed spinal cord decompression. The patient’s symptoms were alleviated, and he has not had a recurrence or cervical instability in the 7 years since his surgery.Discussion:We successfully used a transdural approach in the present case and have observed no recurrence for 7 years postoperatively. C1 laminectomy is reportedly beneficial, especially for elderly patients, given the risk of other surgical options using an anterior transoral approach or posterior fusion. However, most tumors do not attenuate after C1 laminectomy alone; hence, we think that tumor resection by the transdural approach is one effective method to perform enucleation of the tumor after C1 laminectomy.