Application and Advantages of the Trans-Unco-Discal (TUD) Approach for Cervical Spondylotic Myelopathy and Radiculopathy: Classification and Modification of Surgical Technique Based on the Location of Spinal Cord and/or Nerve Root Compression.

Purpose: We assess the application and advantages of modifying the trans-unco-discal (TUD) approach which we underwent for cervical myelo-radiculopathy. We present the surgical techniques of the modified TUD approach. Materials and Methods: The material was 180 cases where anterior cervical decompression (ACD) was performed by the modified TUD approach. We classified the material into four groups based on the location of the nerve root and/or spinal cord compression: I, compression of the root at intervertebral foramen (IVF); II, compression of the posterior margin of the vertebral body; III, compression of the IVF and posterior margin of the vertebral body; IV, compression of the bilateral IVF and posterior margin of the vertebral body. We applied the modified TUD approach to these four types. We present the surgical procedures and techniques for the modified TUD approach. The Japanese orthopedic association (JOA) score and neuroradiological alignment were examined. Results: The improvement rate of the JOA score was 78.4% at 6 months post-surgery and 77.5% in the most recent examinations. By the modified TUD approach, compressive lesions of the spinal cord and/or nerve roots were removed, and good alignment was acquired and sustained. Conclusions: ACD by the modified TUD approach safely achieved appropriate decompression for the spinal cord and/or nerve roots, and the patients had a high improvement rate and good alignment. Complications were less common than with other surgical procedures. If the TUD approach and endoscopic approaches can be combined, their application to new area is anticipated.

Epidemiology and Comparative Analysis of Outcomes of Intramedullary Spinal Cord Tumor Between Pediatric and Adult Patients.

STUDY DESIGN: This was as clinical retrospective study. OBJECTIVES: We sought to evaluate the characteristics of Pediatric intramedullary spinal cord tumors (PISCTs) and to identify differences between pediatric and adult intramedullary spinal cord tumors. SUMMARY OF BACKGROUND DATA: PISCTs represent a rare clinical entity with limited evidence-base in the literature. METHODS: This study is a subanalysis of the retrospective multicenter observational study authorized by the Neurospinal Society of Japan, including consecutive patients with spinal intramedullary tumors treated surgically at 58 institutions between 2009 and 2020. Data on 1080 intramedullary spinal cord tumors were obtained, consisting of 91 pediatric and 939 adult patients. Survival was compared using Cox hazard regression while clinical differences were evaluated using multivariable logistic regression that controlled for confounders. RESULTS: Pediatric patients had a shorter overall, and progression-free, survival than adults. Pediatric patients with ISCTs were likely to have scoliosis [odds ratio (OR) = 6.49, 95% CI: 2.26-18.7], short preoperative symptom duration (OR = 0.99, 95% CI: 0.98-0.99), lower incidence of paresthesia (OR = 0.41, 95% CI: 0.22-0.77), higher incidence of paresis (OR = 2.10, 95% CI: 1.01-4.35), histopathology of astrocytoma (OR = 2.97, 95% CI: 1.19-7.43), and postoperative functional deterioration upon discharge (OR = 2.83, 95% CI: 1.43-5.58). Age was not a statistically significant prognostic factor of overall survival among the pediatric cohort. CONCLUSION: We found that the clinical characteristics of ISCTs differed between pediatric and adult patients. In terms of histopathological types, astrocytoma was most common in pediatric patients. ISCT occurring at an early age may not be an indicator for poor prognosis.

Impact of surgical treatment for intramedullary spinal cord metastasis on neurological function and survival: A multicenter retrospective study by the Neurospinal Society of Japan.

BACKGROUND: This retrospective multicenter study aimed to analyze the characteristics and surgical outcomes of intramedullary spinal cord metastasis (ISCM) and to discuss the controversy regarding its surgical indications. METHODS: This study included 29 ISCM patients who underwent surgery between 2009 and 2020. Biopsy cases were excluded from analysis. For functional and neurological functional assessments, Karnofsky Performance Status (KPS, %) and modified McCormick Scale (MMS, 5-grade scale) scores were determined before and after surgery. Patients were divided into two groups: a mild-to-moderate disability group with preoperative MMS grades 1 to 3, and a severe disability group with preoperative MMS grades 4 to 5. RESULTS: The mean preoperative KPS was 45.9, and the mean duration from symptom onset to surgical intervention was 1 month. The ISCM was located in the cervical spine in 10 cases and the thoracic spine in 19 cases. The access route (myelotomy) for ISCM removal was via the posterior median sulcus in 9 cases and via the posterior lateral sulcus in 11 cases, while others were not recorded. The degree of removal was gross total resection in 20 patients (69%), subtotal resection in 0 patients, and partial removal in 9 patients (31%). No significant complications related to the surgical procedures were recorded. Postoperative adjuvant therapy included radiotherapy in 17 patients (58.6%) and chemotherapy or molecular targeted therapy in 13 patients (44.8%). Pathological findings of ISCM showed that colorectal cancer was the most common in 9 cases, followed by lung cancer in 7, renal cell carcinoma in 5, and breast cancer in 2. Twenty-one of the 29 patients (72.4%) were confirmed to have survived 6 months after surgery: 8 of the 10 patients (80%) in the mild-to-moderate disability group and 13 of the 19 patients (68.4%) in the severe disability group. At 6 months after surgery, 3 of the 8 patients (38%) in the mild-to-moderate group were able to maintain or improve their function. Eleven of the 13 patients (85%) in the severe disability group maintained their function despite being severely disabled. CONCLUSIONS: This study suggests that surgical treatment can maintain or improve neurological function in a limited number of patients with ISCM, although it had minimal impact on improving the survival rate after surgery.

Predictors of Progression-Free Survival in Patients With Spinal Intramedullary Ependymoma: A Multicenter Retrospective Study by the Neurospinal Society of Japan.

BACKGROUND AND OBJECTIVES: Ependymoma is the most common spinal intramedullary tumor. Although clinical outcomes have been described in the literature, most of the reports were based on limited numbers of cases or been confined to institutional experience. The objective of this study was to analyze more detailed characteristics of spinal intramedullary ependymoma (SIE) and provide clinical factors associated with progression-free survival (PFS). METHODS: This retrospective observational multicenter study included consecutive patients with SIE in the cervical or thoracic spine treated surgically at a total of 58 institutions between 2009 and 2020. The results of pathological diagnosis at each institute were confirmed, and patients with myxopapillary ependymoma, subependymoma, or unverified histopathology were strictly excluded from this study. Outcome measures included surgical data, surgery-related complications, postoperative systemic adverse events, postoperative adjuvant treatment, postoperative functional condition, and presence of recurrence. RESULTS: This study included 324 cases of World Health Organization grade II (96.4%) and 12 cases of World Health Organization grade III (3.6%). Gross total resection (GTR) was achieved in 76.5% of cases. Radiation therapy (RT) was applied after surgery in 16 cases (4.8%), all of which received local RT and 5 of which underwent chemotherapy in combination. Functional outcomes were significantly affected by preoperative neurological symptoms, tumor location, extent of tumor resection, and recurrence. Multivariate regression analysis suggested that limited extent of tumor resection or recurrence resulted in poor functional outcomes. Multiple comparisons among the groups undergoing GTR, subtotal resection and biopsy, or partial resection of the tumor showed that the probability of PFS differed significantly between GTR and other extents of resection. CONCLUSION: When GTR can be safely obtained in the surgery for SIE, functional maintenance and longer PFS can be expected.

Cervical Lift-up Basket Laminoplasty after Resection of Spinal Intramedullary Tumors: A Finite Element Analysis and Clinical Image Evaluation.

Although reconstructive laminoplasty is commonly performed after resection of spinal intramedullary tumors of the cervical spine, its biomechanical rigidity of laminoplasty framework remains unclear. The objective of this study was to examine the structural reliability of our unique method of cervical lift-up basket laminoplasty by using computed tomography (CT)-based finite element analysis (FEA) and clinical radiological evaluation. A finite element model of cervical laminoplasty was created based on CT images using FEA software. Cervical lift-up basket laminoplasty (Basket) was compared with the standard style of open-door basket laminoplasty (Open-door). Clinical subjects for radiological evaluation comprised 33 patients who underwent cervical lift-up basket laminoplasty after resection of spinal intramedullary tumors. An FEA-equivalent stress histogram showed that stress was moderately dispersed around the basket. Virtual displacement of the spinous process of the Basket model was equivalent to that of the Open-door model in any direction of posterior-to-anterior, right-to-left, or top-to-bottom force. In the clinical analysis, radiological data with a minimum postoperative period of 6 months were obtained in a total of 28 out of 33 patients. No patients underwent revision surgery because of implant-related complications. No significant differences in C2-C7 angle or cervical tilt angle were observed between pre- and postoperatively. The structural rigidity of cervical lift-up basket laminoplasty was equivalent to the open-door style on the FEA. Clinical radiological evaluation suggested that there were no serious adverse events associated with cervical laminoplasty, although the longer postoperative follow-up is mandatory.

Anatomical Limitation of Posterior Spinal Myelotomy for Intramedullary Hemorrhage Associated with Ependymoma or Cavernous Malformation of the High Cervical Spine.

Spinal intramedullary tumors such as ependymoma or vascular lesions such as cavernous malformation are often at risk of intramedullary hemorrhage. Surgical procedures involving the high cervical spinal cord are often challenging. This technical note included four patients who presented with acute, subacute, or gradual onset of spinal cord dysfunction associated with intramedullary hemorrhage at the C1 or C1/2 level of the high cervical spine. The mean age was 46.3 years (16-74 years). All patients underwent posterior spinal cord myelotomy of the posterior median sulcus or posterolateral sulcus. It was not to exceed the caudal opening of the fourth ventricle (foramen of Magendie) and was assumed to be as high as the caudal medulla oblongata. Total removal of the intramedullary ependymoma or cavernous malformation occurred in three of four cases, and the remaining case had subtotal removal of the ependymoma. None of the patients showed postoperative deterioration of the neurological condition. Pathological examination of all cases revealed intramedullary hemorrhage was associated with ependymoma or cavernous malformation. Posterior spinal myelotomy should be limited to the caudal opening of the fourth ventricle (foramen of Magendie), that is the caudal medulla oblongata, to avoid the significant deterioration after surgery.

Rhamnazin suppresses melanosome transport by promoting the ubiquitin-mediated proteasomal degradation of melanophilin.

BACKGROUND: Melanosomes are intracellularly transported from the perinuclear region to the cell periphery and then to neighboring keratinocytes. We recently reported that the flavonoid rhamnazin suppresses melanosomal transport within pigment cells, yet the action mechanism remained unclear. OBJECTIVE: Our aim was to elucidate how rhamnazin influences the intracellular transport of melanosomes. METHODS: A melanosome distribution assay and immunostaining were performed using B16F10 mouse melanoma cells and normal human epidermal melanocytes, respectively. Expression levels of melanosome transport-related proteins, including melanophilin (MLPH), RAB27A, and myosin VA (MYO5A), were analyzed by immunoblotting. Ubiquitinated MLPH was detected using a commercial ubiquitin detection kit. To investigate the interaction between rhamnazin and MLPH, we prepared rhamnazin conjugated with magnetic FG beads. RESULTS: Immunoblotting analysis revealed that rhamnazin specifically reduces the expression of MLPH but not RAB27A or MYO5A proteins. The ubiquitin detection assay, which made use of a proteasome inhibitor, showed that MLPH accumulated as a polyubiquitinated protein after treatment with rhamnazin. We speculated that the affinity of rhamnazin for the components of the melanosome transport-related tripartite complex may alter the stability of the formation of the tripartite assembly. By using affinity-based techniques with B16F10 whole cell lysates or recombinant MLPH and RAB27A proteins, we revealed the interaction of rhamnazin with the components of the tripartite complex. CONCLUSION: We found that rhamnazin inhibits intracellular transport of melanosomes through proteasomal degradation of MLPH. Our results suggest that topical application of rhamnazin may provide a new approach for treating skin pigmentation disorders.

[Key of Classification and Diagnosis of Spinal Arteriovenous Malformation].

Spinal arteriovenous malformation(AVM)is a rare disease in which blood is received from the spinal feeding arteries. Owing to its rarity, there is limited experience regarding its diagnosis and treatment. In addition, the various classifications that have been proposed historically make it more difficult for the young neurosurgeons to understand this disease. Because delayed initial diagnosis leads to irreversible damage of the spinal cord, neurosurgeons should always consider spinal AVM as one of the differential diagnoses. In order to understand the pathological condition of spinal AVM, it is important to learn basic classification. Spinal AVM is classified as intradural, dural, and epidural. Spinal digital subtraction angiography(DSA)is the gold-standard for the diagnosis of spinal AVM and is indispensable toolfor treatment planning. The purpose of this paper is to summarize a basic classification and diagnosis of spinal AVM.

Spinal cord astroblastoma with EWSR1-BEND2 fusion classified as HGNET-MN1 by methylation classification: a case report.

The most recurrent fusion of central nervous system high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) is MN1 rearrangement. Here, we report the case of a 36-year-old man with spinal cord astroblastoma showing Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1)-BEN domain-containing 2 (BEND2) fusion. The patient presented with back pain, gait disturbance and dysesthesia in the lower extremities and trunk. Magnetic resonance imaging showed an intramedullary tumor at the T3-5 level, displaying homogeneous gadolinium enhancement. Partial tumor removal was performed with laminectomy. Histological examinations demonstrated solid growth of epithelioid tumor cells showing high cellularity, a pseudopapillary structure, intervening hyalinized fibrous stroma, and some mitoses. Astroblastoma was diagnosed, classified as HGNET-MN1 by the German Cancer Research Center methylation classifier. MN1 alteration was not detected by fluorescence in situ hybridization (FISH), but EWSR1-BEND2 fusion was detected by FISH and RNA sequencing. Previously, a child with EWSR1-BEND2 fusion-positive spinal astroblastoma classified as HGNET-MN1 was reported. In conjunction with that, the present case provides evidence that EWSR1-BEND2 fusion is identified in the entity of HGNET-MN1. Taken together, the BEND2 alteration rather than MN1 may determine the biology of a subset of the central nervous system HGNET-MN1 subclass.

Restoring NAD+ by NAMPT is essential for the SIRT1/p53-mediated survival of UVA- and UVB-irradiated epidermal keratinocytes.

Nicotinamide adenine dinucleotide (NAD+) is a crucial coenzyme in energy production. The imbalance of NAD+ synthesis has been found to trigger age-related diseases, such as metabolic disorders, cancer, and neurodegenerative diseases. Also, UV irradiation induces NAD+ depletion in the skin. In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD+ salvage pathway and essential for NAD+ homeostasis. However, but few studies have focused on the role of NAMPT in response to UV irradiation. Here, we show that NAMPT prevents NAD+ depletion in epidermal keratinocytes to protect against the mild-dose UVA and UVB (UVA/B)-induced proliferation defects. We showed that poly(ADP-ribose) polymerase (PARP) inhibitor rescued the NAD+ depletion in UVA/B-irradiated human keratinocytes, confirming that PAPR transiently exhausts cellular NAD+ to repair DNA damage. Notably, the treatment with a NAMPT inhibitor exacerbated the UVA/B-induced loss of energy production and cell viability. Moreover, the NAMPT inhibitor abrogated the sirtuin-1 (SIRT1)-mediated deacetylation of p53 and significantly inhibited the proliferation of UVA/B-irradiated cells, suggesting that the NAMPT-NAD+-SIRT1 axis regulates p53 functions upon UVA/B stress. The supplementation with NAD+ intermediates, nicotinamide mononucleotide and nicotinamide riboside, rescued the UVA/B-induced phenotypes in the absence of NAMPT activity. Therefore, NAD+ homeostasis is likely essential for the protection of keratinocytes from UV stress in mild doses. Since the skin is continuously exposed to UVA/B irradiation, understanding the protective role of NAMPT in UV stress will help prevent and treat skin photoaging.

Combination of p53 and Ki67 as a Promising Predictor of Postoperative Recurrence of Meningioma.

BACKGROUND: Meningioma is a common intracranial tumor originating from arachnoid cap cells. Meningiomas are generally benign tumors curable by one-time resection. However, some meningiomas regrow and invade into the dura mater, and thus frequently require additional treatment. A useful marker to predict the regrowth of meningioma is desired. This study aimed to clarify the significance of p53 and Ki67 for postoperative recurrence of meningioma. MATERIALS AND METHODS: The expression of p53 and Ki67 in 215 intracranial or intraspinal meningiomas was investigated by immunohistochemistry. RESULTS: Of the 215 meningiomas, 35 cases (16.3%) were p53-positive and 49 cases (22.8%) were Ki67-positive. Multivariate analysis revealed Ki67 and p53 status as being significantly correlated with recurrence. Positivity for either Ki67- or p53 was significantly associated with poor recurrence-free survival. CONCLUSION: Combined p53 and Ki67 status might represent a useful independent predictive marker for recurrence of meningioma.

Microsurgical or endovascular strategy for complete obliteration of spinal arteriovenous shunts in a single-institute 10-year retrospective study.

The objective of this retrospective study is to more fully understand the optimal strategy to manage spinal arteriovenous (AV) shunts. This study included a cohort of 35 patients with a diagnosis of spinal AV shunts who were treated over the past 10 years at a single institute. Angiographic diagnosis of intramedullary AV malformations (IM-AVM), perimedullary AV fistulas (PM-AVF), dural AV fistulas (D-AVF), or epidural AV fistulas (ED-AVF) was carefully made, and the microsurgical or endovascular strategy for them was determined at the interdisciplinary meeting consisting of neurospinal surgeons and endovascular specialists. Endovascular surgery was first considered whenever safely possible. Microscopic direct surgery using intraoperative image guidance was considered for cases in which endovascular access was challenging or not safely possible. Combined treatment was another option. The clinical condition was assessed using the modified Rankin scale (mRS). Seventeen of 35 cases were treated with microscopic direct surgery, 13 cases with endovascular surgery, and the remaining five cases with the combination. Complete angiographic obliteration was achieved in 30 of 35 cases (85.7%). Although residual AV shunts was recognized in 3 cases of IM-AVM, 1 case of PM-AVF and 1 case of ED-AVF, no angiographic recurrence was present with an average postoperative follow-up period of 44 months. The average mRS before surgery was 2.37 and significantly improved to 1.94 at the most recent follow-up. Interdisciplinary collaboration between neurospinal surgeons and endovascular specialists should be standard to achieve safe and successful outcomes in treating such rare and difficult spinal disorders.

Posterior Direct Reduction of Lateral Atlantoaxial Joints for Rigid Pediatric Atlantoaxial Subluxation: A Fulcrum Lever Technique.

STUDY DESIGN: Clinical case series. OBJECTIVE: To present a surgical technique and results of posterior direct reduction of lateral atlantoaxial joints for rigid pediatric atlantoaxial subluxation (AAS) using a fulcrum lever technique. SUMMARY OF BACKGROUND DATA: The surgical treatment of pediatric rigid AAS is still technically challenging. Several factors contribute to the surgical difficulty, such as small vertebrae, incomplete bone formation, dysplasia, the difficulty of reduction and external fixation are considered as a surgical daunting challenge. Herein, the surgical technique of posterior direct reduction of lateral atlantoaxial joints for rigid pediatric AAS using a fulcrum lever technique is presented. METHODS: This retrospective study included 10 pediatric patients with rigid AAS who underwent posterior direct reduction of bilateral C1/2 facet joints via a fulcrum lever technique. The indication for surgery was the presence of neurological symptoms and spinal cord atrophy with an intramedullary high signal at the C1 level on T2-weighted magnetic resonance (MR) images. The surgical procedure consisted of three steps: (1) opening and distraction of the C1/2 facet joints and placement of tricortical bone as a spacer and fulcrum; (2) placement of C1 and C2 screws; and finally, (3) compression between the C1 posterior arch and C2 lamina and constructing C1/2 fusion. All patients underwent the neurological and radiological evaluations before and after surgery. RESULTS: Eight of 10 patients demonstrated genetic disorders, either Down syndrome or chondrodysplasia punctate. Besides, all cases documented congenital anomaly of the odontoid process. Bilateral C1 lateral mass screws were successfully placed in all cases. No evidence of postoperative neurovascular complications. Radiological evaluation showed the corrections and bony fusions of C1/2 facet joint in all cases. CONCLUSION: The fulcrum lever technique for rigid pediatric AAS can be one of the effective surgical solutions to this challenging pediatric spinal disorder. LEVEL OF EVIDENCE: 4.

Low recurrence after Simpson grade II resection of spinal benign meningiomas in a single-institute 10-year retrospective study.

The objective of this study was to more fully understand the optimal neurosurgical strategy for spinal benign meningiomas from a medium to long-term perspective. This retrospective study included a cohort of 35 patients with a diagnosis of spinal meningioma who were first operated at our institute over the past 10 years and followed-up for at least 2 years after surgery. The inclusion criterion for the study was the pathological diagnosis finally verified as benign meningioma of World Health Organization (WHO) grade 1. The average follow-up duration after surgery was 61.0 months. The location of the spinal meningioma was classified into ventral or dorsal type based on the operative video record and the preoperative MR images. The extent of resection of the spinal meningioma was carefully determined based on the Simpson grade. The average neurological condition was significantly improved at the final follow-up. Simpson grade I or II resection was achieved in 31 of 35 cases (88.6%). No Simpson grade I or II cases showed local recurrence during follow-up. Tumor recurrence was noted in 2 of 4 cases of Simpson grade IV resection. One case has been followed-up without any re-operation because of no neurological deterioration, and the other case underwent stereotactic radiosurgery. This study suggested that meticulous Simpson grade II resection of spinal benign meningiomas of WHO grade 1 may be good enough from a medium to long-term follow-up perspective, though longer follow-up is absolutely necessary.

Health-Related Quality of Life After Microscopic Total Removal of Spinal Intramedullary Ependymomas in a Single-Institute 3-Year Prospective Study.

OBJECTIVE: Health-related quality of life (HRQOL) after surgery for spinal intramedullary benign encapsulated tumors remains unclear. A single-institute, 3-year, prospective study was conducted to examine HRQOL after microscopic total removal of spinal intramedullary ependymomas using a safe and precise strategy. METHODS: A cohort of 20 patients with a possible diagnosis of spinal intramedullary benign ependymomas was recruited. Patients who underwent microscopic total removal of the tumor and for whom the pathologic diagnosis was verified as World Health Organization grade II benign ependymoma were included. Sixteen patients (average age, 48.7 years) were eligible for study analysis. Careful assessment was performed for all patients before and 6-12 months after surgery. The 36-Item Short Form Health Survey was used to assess HRQOL, with the surveyor recording answers as reported by the individual patient. RESULTS: Average total HRQOL score was 431.1 before surgery and was maintained at 434.2 at 6-12 months postoperatively. Patients with mild functional symptoms tended to demonstrate a higher total HRQOL score preoperatively compared with patients with moderate to severe functional symptoms. A strong correlation was noted between postoperative functional conditions and preservation of HRQOL. CONCLUSIONS: This is the first study focusing on HRQOL after microscopic total removal of spinal intramedullary ependymomas. This study suggested that radical surgery using a safe and precise strategy appears justifiable and that preservation of neurologic function after surgery may lead to maintenance of postoperative HRQOL.

Safety of anterior cervical discectomy and fusion using titanium-coated polyetheretherketone stand-alone cages: Multicenter prospective study of incidence of cage subsidence.

This multicenter prospective study investigated cage subsidence in anterior cervical discectomy and fusion (ACDF) using titanium-coated polyetheretherketone (PEEK) stand-alone cages. This study recruited patients who underwent 1- or 2-level ACDF using titanium-coated PEEK stand-alone cages for cervical disc disease. Patients with acute trauma or past cervical spine operations were excluded. Sixty-two cages in 42 patients were eligible for analysis. Minimum follow-up was 6 months after ACDF. Significant cage subsidence was recognized in 11 of 62 cages (17.7%). Cage subsidence was predominantly moderate (14.5%), with severe subsidence found in only 2 cages (3.2%). The slowest occurrence of cage subsidence was 6 months after surgery, in 4 of 11 cages. Frequency of cage subsidence did not differ significantly between patients <65 and ≥65 years old. Patients with and without cage subsidence both demonstrated significant improvement of neurological function. Cage subsidence resulted in aggravation of local angle, but finally did not affect C2-7 angle or cervical tilt angle. Severe cage subsidence was found in only 3.2% of patients within 6 months after ACDF. Cage subsidence aggravated local angle, but finally did not affect C2-7 angle or cervical tilt angle. One- or 2-level ACDF using titanium-coated PEEK stand-alone cages appears safe and justified, even in elderly patients.

Tomatidine Reduces Palmitate-Induced Lipid Accumulation by Activating AMPK via Vitamin D Receptor-Mediated Signaling in Human HepG2 Hepatocytes.

SCOPE: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide, defined by hepatic over-accumulation of lipids without significant ethanol consumption. Pharmacological or bioactive food ingredients that suppress hepatic lipid accumulation through AMP-activated protein kinase (AMPK) signaling, which plays a critical role in the regulation of lipid metabolism, are searched. METHODS AND RESULTS: It is found that tomatidine, the aglycone of α-tomatine abundant in green tomatoes, significantly inhibits palmitate-provoked lipid accumulation and stimulates phosphorylation of AMPK and acetyl-CoA carboxylase 1 (ACC1) in human HepG2 hepatocytes. The results also indicate that tomatidine can enhance triglyceride turnover and decline in lipogenesis by upregulating adipose triglyceride lipase (ATGL) and downregulating fatty acid synthase (FAS) via the AMPK signaling-dependent regulation of transcription factors, element-binding protein-1c (SREBP-1c) and forkhead box protein O1 (FoxO1). Furthermore, mechanistic studies demonstrate that tomatidine-stimulated AMPK phosphorylation is due to CaMKKß activation in response to an increase in intracellular Ca2+ concentration. Finally, it is discovered that tomatidine functions as an agonist for vitamin D receptor to elicit AMPK-dependent suppression of lipid accumulation. CONCLUSION: The in vitro study suggests the potential efficacy of tomatidine as a preventive and therapeutic treatment in obesity-related fatty liver diseases.

High Cervical Lateral Approach to Safely Remove the Cystic Retro-odontoid Pseudotumor: Technical Note.

Surgery for neoplastic or vascular lesions at the craniovertebral junction remains one of the major challenges for neurosurgeons, because of issues such as the complex functional anatomy and vascular structures. We present three cases in which the high cervical lateral approach was used to safely remove the cystic retro-odontoid pseudotumor, not associated with rheumatoid arthritis, severely compressing the spinal cord. The mean age of patients was 74.7 years (range, 73-77 years). Neurological condition was assessed based on the neurosurgical cervical spine scale. A high cervical lateral approach was applied to remove the pseudotumor safely. Mean duration of follow-up after surgery was 21.3 months (range, 18-24 months). Mean recovery rate was 77.8%. All patients showed acceptable or satisfactory functional recovery, although one patient (Case 2) developed mild paralysis of the facial and spinal accessory nerve on the surgical approach side, but that completely recovered within about 1 month after surgery. Postoperative assessment at the recent follow-up suggested no significant aggravation of neck movement. This technical note suggests that the high cervical lateral approach can be considered as a surgical option for cystic retro-odontoid pseudotumor, not associated with rheumatoid arthritis, severely compressing the spinal cord. Safe management of the vertebral artery is one of the key considerations.

Safety and Efficacy of Syringoperitoneal Shunting with a Programmable Shunt Valve for Syringomyelia Associated with Extensive Spinal Adhesive Arachnoiditis: Technical Note.

OBJECTIVE: Although syringomyelia associated with extensive spinal adhesive arachnoiditis (SAA) can be a progressive disease that has potentially devastating clinical consequences, its surgical resolution has remained poorly defined. The aim of the present study was to verify the safety and efficacy of syringoperitoneal shunting for syringomyelia associated with extensive SAA. METHODS: The present retrospective study included 15 patients who had undergone syringoperitoneal shunting with a programmable shunt valve for the diagnosis of syringomyelia associated with extensive SAA from October 2012 to June 2018. The shunt pressure was appropriately adjusted according to the postoperative sequential clinical condition and change in syringomyelia evaluated using magnetic resonance imaging. The average postoperative follow-up duration was 32.7 months. RESULTS: No surgery-related complications such as shunt dysfunction or infection occurred during the follow-up period, except for 2 patients with minor issues with the shunt tube. The average shunt pressure at the last follow-up examination was 4.5 cm H2O. The findings from the clinical assessment suggested that the average grade on the sensory pain scale was 2.9 before surgery and had improved significantly to 2.5 at the most recent follow-up examination. Radiological analysis suggested that improvement of syringomyelia was noted in 14 of the 15 patients (93.3%), with no cases of radiological aggravation. No recurrence of syringomyelia developed during the follow-up period in the present study. CONCLUSION: Syringoperitoneal shunting with a programmable shunt valve was safe and effective for clinical control of syringomyelia associated with extensive SAA. Long-term follow-up is mandatory to monitor for shunt dysfunction and mechanical trouble.