Sequential Expression of Chemokines in Chronic Subdural Hematoma Fluids after Trepanation Surgery.

Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Chemokines attract leukocytes, and invading neutrophils and monocytes/macrophages play important roles in wound healing. However, no studies have been reported regarding changes in expression of chemokines in CSDH fluid after trepanation surgery. We randomly divided patients who underwent trepanation surgery into two groups. One was the irrigation group, in which irrigation of CSDH fluids was performed and a drainage tube was placed (n = 10). The other was the non-irrigation group, in which a drainage tube was inserted without irrigation (n = 10). CSDH fluids were collected during the trepanation surgery, immediately after surgery and on day 1 through the drainage tube. The concentrations of interleukin-8 (IL-8), growth-regulated oncogene-α (GRO-α), epithelial neutrophil-activating peptide 78 (ENA-78), monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein-10 (IP-10), tissue plasminogen activator (tPA), von Willebrand factor (vWF), eotaxin-3, and myeloperoxidase (MPO) in each CSDH fluid sample were measured using enzyme-linked immunosorbent assay kits. After irrigation, concentrations of all chemokines decreased. However, concentrations of IL-8, GRO-α, ENA-78, MCP-1, and MPO were significantly increased on day 1 compared with concentrations during surgery with or without irrigation. In contrast, there were no changes in concentrations of IP-10, eotaxin-3, tPA, or vWF after trepanation surgery. Moreover, there were significant relationships among concentrations of IL-8, GRO-α, ENA-78, and MCP-1 during the surgery and on day 1. In CSDH fluids, chemokines that attract neutrophils, such as IL-8, GRO-α, ENA-78, and macrophage-attracting MCP-1, appear first after trepanation surgery, whereas lymphocyte-attracting IP-10 and eosinophil-attracting eotaxin-3 levels do not change within 1 day of surgery. These findings suggest that neutrophils and macrophages may play important roles in the healing process of CSDH at an early stage.

Efficacy of Endovascular Proximal Occlusion before Direct Reposition Surgery of Blunt Cervical Fracture with Unilateral Vertebral Injury.

Cerebral infarction related to traumatic vertebral artery (VA) injuries is not common. However, if VA injuries cause ischemic and/or hemorrhage stroke, these subsequent problems can result in severe residual impairment and mortality. Herein, we present five patients with cervical vertebra fractures due to blunt cervical trauma who underwent preoperative endovascular therapy. Between June 2010 and April 2018 in our hospital, five patients with traumatic occlusion of a unilateral VA underwent coil embolization to prevent post-surgical stroke due to reperfusion in the VA. Because of cervical instability or subluxation, all of the patients received endovascular therapy before surgery for their cervical fracture. None of the patients presented with stroke after presurgical embolization and direct surgery. When stagnated blood, including thrombi, in the occluded VA is released during cervical surgery, brain embolism may occur. Therefore, early cerebrovascular vessel assessment and presurgical endovascular treatment must be considered to prevent stroke after direct surgery.

Interleukin-6, MCP-1, IP-10, and MIG are sequentially expressed in cerebrospinal fluid after subarachnoid hemorrhage.

BACKGROUND: Interleukin-6 (IL-6), an inflammatory cytokine, plays important roles in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). Chemokines are chemoattractant cytokines that regulate trafficking of monocytes/macrophages and lymphocytes to sites of inflammation. However, no studies have been reported regarding the temporal expression of these cytokines in CSF after SAH. FINDINGS: The concentrations of IL-6, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-inducible protein-10 (IP-10), and monokine induced by interferon-γ (MIG) in the CSF of ten patients with SAH were measured using ELISA kits over a period of 14 days. All aneurysms were located in the anterior circulation. CSF samples from patients with unruptured aneurysms were used as controls. The concentration of IL-6 significantly increased during the acute stage of the disease. The concentration of MCP-1 increased from days 1 to 5, peaking on day 3, and decreased thereafter. The concentrations of IP-10 and MIG progressively increased, peaked on day 5, and then gradually decreased. There were strong correlations between the maximum levels of IL-6 and MCP-1 and IP-10 and MIG on day 5. The maximum level of IL-6 was much higher in poor outcome patients than in good outcome patients. CONCLUSIONS: The present investigation demonstrated that increases in IL-6 levels may induce the expression of MCP-1 in CSF after SAH, followed by increases in the expression of IP-10 and MIG. Dynamic changes in the levels of these cytokines may induce inflammation and may be closely associated with the development of delayed ischemic neurological deficits after SAH.

Medulloblastoma with epithelioid features in the cerebellar vermis.

A 6-year-old girl was admitted with a mass lesion in the cerebellar vermis. She underwent subtotal tumor resection, and on immunohistopathology the tumor consisted of two different parts: typical medulloblastoma (MB) characteristics and atypical teratoid/rhabdoid tumor (AT/RT) features, despite positive integrase interactor 1 expression. The patient was diagnosed with MB with epithelioid features. Chemoradiation therapy was started because of tumor recurrence at the primary site and dissemination to the spinal cord, as determined on magnetic resonance imaging 2 weeks after surgery. The patient died due to tumor progression 13 months after initial diagnosis, although transient partial remission was achieved.

Installation of a Neuromate Robot for Stereotactic Surgery: Efforts to Conform to Japanese Specifications and an Approach for Clinical Use-Technical Notes.

The neuromate is a commercially available, image-guided robotic system for use in stereotactic surgery and is employed in Europe and North America. In June 2015, this device was approved in accordance with the Pharmaceutical Affairs Law in Japan. The neuromate can be specified to a wide range of stereotactic procedures in Japan. The stereotactic X-ray system, developed by a Japanese manufacturer, is normally attached to the operating table that provides lateral and anteroposterior images to verify the positions of the recording electrodes. The neuromate is designed to be used with the patient in the supine position on a flat operating table. In Japan, deep brain stimulation surgery is widely performed with the patient's head positioned upward so as to minimize cerebrospinal fluid leakage. The robot base where the patient's head is fixed has an adaptation for a tilted head position (by 25 degrees) to accommodate the operating table at proper angle to hold the patient's upper body. After these modifications, the accuracy of neuromate localization was examined on a computed tomography phantom preparation, showing that the root mean square error was 0.12 ± 0.10 mm. In our hospital, robotic surgeries, such as those using the Da Vinci system or neuromate, require operative guidelines directed by the Medical Risk Management Office and Biomedical Research and Innovation Office. These guidelines include directions for use, procedural manuals, and training courses.

Expression of Mitogen-Activated Protein Kinases in Chronic Subdural Hematoma Outer Membranes.

Growth factors and inflammatory cytokines activate the mitogen-activated protein kinase (MAPK) cascade. Previous studies have shown that chronic subdural hematoma (CSDH) fluid contains these factors and cytokines. In this study, expression of three major MAPK cascade transmitters in the outer membrane of CSDH was assessed. Eleven patients whose outer membrane and CSDH fluid were successfully obtained during trepanation surgery were included in this study. Expression of extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK), p-JNK, and actin was examined by Western blot and immunostaining. We examined whether CSDH fluid could activate MAPKs in cultured endothelial cells (ECs) or fibroblasts in vitro. Western blot analysis showed that p-ERK was present in all samples, whereas p-p38 and p-JNK were detected, but not in all cases. Immunostaining showed that all three p-MAPKs were expressed in vascular endothelium. However, only p-ERK was expressed in fibroblasts. Expression of p-extracellular signal-regulated kinase kinase (MEK) and p-ERK in ECs and fibroblasts was significantly induced immediately after treatment with CSDH fluid, whereas p-p38 and p-JNK expression was significantly induced in ECs 60 min after treatment, but not in fibroblasts. Activation of MEK was significantly inhibited by treatment with antibodies directed against interleukin-6 and vascular endothelial growth factor in ECs, but not in fibroblasts. Inflammatory cytokines and growth factors in CSDH fluids might activate major MAPKs in ECs, which might be associated with neovascularization in the outer membrane of CSDH. These MAPK pathways could become novel targets for treatment of CSDHs.

Expression of suppressor of cytokine signaling 3 in cerebrospinal fluid after subarachnoid hemorrhage.

BACKGROUND: IL-6 is a proinflammatory cytokine reported to play an important role in the induction of cerebral vasospasm after subarachnoid hemorrhage (SAH). Suppressor of cytokine signaling 3 (SOCS3) is known to act as an inhibitor of signal transduction of IL-6. However, there have been no reports on the expression of SOCS3 in cerebrospinal fluid (CSF) after SAH. FINDINGS: The concentration of IL-6 was measured serially up until day 10, in CSF of eight patients with SAH. CSF samples obtained from patients suffering from an unruptured aneurysm were used as controls. The expression of SOCS3 in CSF was further examined by immunoprecipitation methods. Concentrations of IL-6 in CSF increased immediately after the onset of SAH and remained chronically elevated over control values. SOCS3 was significantly expressed in CSF on days 1 to 3 after SAH. CONCLUSIONS: Our findings suggest that SOCS3 regulates IL-6 signaling as an antagonist in CSF, immediately following SAH. As the expression of SOCS3 decreases after day 5, IL-6 signals might then be more easily transmitted, presumably resulting in cerebral vasospasm.

Plasmapore-coated titanium cervical cages induce more rapid and complete bone fusion after anterior cervical discectomy and fusion as compared to noncoated titanium cages.

OBJECTIVE: The aim of this study was to examine the solid bone fusion rates between Plasmapore-coated titanium cages (PPC group) and non-Plasmapore-coated titanium cages (N-PPC group) in patients who received anterior cervical decompression and fusion (ACDF). METHODS: Of 78 patients who received ACDF at the hospital, a follow-up period greater than 2 years was possible for 61 patients, including 30 in the PPC group and 42 in the N-PPC group. Evaluations were performed at 3, 6, 12, and 24 months after surgery. Radiological stabilization (RS) was defined as the restriction of spinous process movement to <3 mm and the absence of a halo around the cages on flexion-extension radiographs. Solid bone fusion (SBF) was defined as the formation of bony bridges between the fixed vertebral bodies in sagittal computed tomography sections. The rates of RS and SBF were compared between both groups. RESULTS: The differences in RS were not significant between the 2 groups during the follow-up period. However, the SBF rates at 6 and 12 months were significantly higher in the PPC group (26.7% and 56.7%) than in the N-PPC group (5% and 21.4%). Moreover, 63.3% (19 of 30) of patients in the PPC group demonstrated RS at 3 months, and of these patients, SBF was observed in 100% (19 patients) after 24 months, respectively. In comparison, the SBF rates in the N-PPC group were 86%. CONCLUSIONS: Plasmapore-coated titanium cages enabled more rapid solid bone fusion. We suggest that these types of cages might help to reduce postoperative radiograms.

Pathomorphological description of the shunted portion of a filum terminale arteriovenous fistula.

BACKGROUND CONTEXT: The clinical morphology of a filum terminale arteriovenous fistula (f-AVF) is well known; however, pathological details of the fistulized portion are unknown. Herein, we report the pathological findings of the f-AVF. STUDY DESIGN: Case report and literature review. PURPOSE: To present a detailed pathological examination of the fistulized portion of the f-AVF. METHODS: A 71-year-old man presented with gradually worsening bilateral foot paresthesias and anal dysesthesia. T2-weighted magnetic resonance imaging showed flow voids surrounding an edematous conus medullaris and cauda equina with spinal stenosis at L3-L4 and L4-L5. Spinal digital subtraction angiography demonstrated an f-AVF fed by the left T9 intercostal artery. RESULTS: We performed laminotomies of L3 and L4 to open the dura mater and found a hypertrophic filum terminale. It was resected, leaving a length of 2 cm between the abnormal proximal end and normal distal end. The f-AVF completely disappeared after the surgery. On pathological examination, the filum terminale included two vessels at the proximal end and one at the distal end. At the proximal end, immunostaining showed one vessel that was definitively an artery with both an internal elastic membrane (IEM) and smooth muscle. The other was a vein and lacked an IEM. On the distal side, the collagen fibers gradually increased, the IEM partially disappeared from the arterial wall, and the vein became arterialized with a thin IEM. At the distal end the two vessels joined. Therefore, we speculated that the fistulized portion of the f-AVF was not a fistula point but had some lengths where the artery had characteristics of a vein and there was venous arterialization. CONCLUSIONS: The filum arteriovenous shunting occurred at the portion where there was venous arterialization and the artery had the characteristics of a vein. Therefore, resecting the filum terminale requires more proximal from the normal distal end.

Activation of Ras/MEK/ERK signaling in chronic subdural hematoma outer membranes.

Chronic subdural hematoma (CSDH) is considered to be an angiogenic disease. Vascular endothelial growth factor (VEGF), one of the important growth factors regulating angiogenesis, is expressed in the neomembranes and also in hematoma fluid, and the Ras/MEK/ERK signaling pathway has been implicated in angiogenesis by VEGF. In the present study, the status of this signaling pathway in CSDH outer membranes was examined using outer membranes obtained during trepanation surgery. The expression levels of Ras, Ras-GAP, c-Raf, MEK, ERK, phosphorylated (p)-ERK, endothelial nitric oxide synthase (eNOS) and actin were examined by western blot analysis; the expression of p-ERK was also examined by immunohistochemistry. Ras, Ras-GAP, c-Raf, MEK, ERK and eNOS were detected in all cases. In addition, the expression of p-ERK was confirmed in all cases, and p-ERK was localized to the endothelial cells of the vessels in CSDH outer membranes. These findings indicated that Ras/MEK/ERK signaling is activated in the CSDH outer membranes and suggested the possibility that the Ras/MEK/ERK pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDHs.

Motor evoked potential study suggesting L5 radiculopathy caused by l1-2 disc herniation: case report.

A 38-year-old male was referred because of pain in the left 5th lumbar (L5) root territory. Physical examination found moderate motor weakness in the left extensor hallucis longus (EHL) and the left tibialis anterior muscles. Magnetic resonance imaging found no stenotic lesion between L4-L5, but disc herniation was observed on the left between L1-L2. An L5 nerve root block provided temporary relief of the pain but the left foot weakness was exacerbated. Therefore, surgery was performed. Partial laminectomy and left herniotomy were performed at L1-L2, L2-L3, and L3-L4 with motor evoked potential (MEP) monitoring. The MEP amplitude of the left EHL muscle increased immediately after L1-L2 herniotomy. The MEP amplitude of the right EHL muscle also increased after both laminectomy and herniotomy. The postoperative course was uneventful. The left leg pain and motor weakness disappeared. The patient has been doing fine without recurrence for 12 months. Since the MEP of both left and right EHL muscles improved after the L1-2 herniotomy, circulatory insufficiency might have caused the L5 symptoms. Monitoring of the MEP during the surgery was useful for confirming the responsible lesion and also for predicting the postoperative course.

Soluble gp130 regulatess interleukin-6 in cerebrospinal fluid after subarachnoid haemorrhage.

BACKGROUND: Interleukin-6 (IL-6) is a proinflammatory cytokine reported to play an important role in induction of cerebral vasospasm after subarachnoid haemorrhage (SAH). Soluble gp130 (sgp130) and soluble IL-6 receptor (sIL-6R) are known to act as signal transducing receptors of IL-6, the former as an antagonist and the latter as an agonist. However, there have been no reports concerning regulation of the IL-6 signalling pathway in cerebrospinal fluid (CSF) after SAH. METHODS: Concentrations of IL-6, sgp130 and sIL-6R were measured serially until day 14 in CSF from nine patients with SAH. CSF samples obtained from patients suffering from unruptured aneurysm were used as controls. Colocalisation of IL-6 and sgp130 in CSF on day 1 was further examined by immunoprecipitaiton. RESULTS: Concentrations of IL-6 in CSF increased immediately after the onset of SAH and remained chronically elevated over control values. Both sgp130 and sIL-6R also exhibited increased on day 1, followed by a decrease limited to the gp130 case after day 5. Sgp130 coimmunoprecipitated with IL-6 in CSF on day 1 after SAH. CONCLUSIONS: Our findings suggest that sgp130 regulates IL-6 signalling as an antagonist in CSF immediately after SAH. As the concentration of sgp130 decreases after day 5, IL-6 signals might then be more easily transmitted, presumably resulting in cerebral vasospasm.