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We determined the feasibility of the combined exoscopic-endoscopic technique (CEE) as an alternative to the microscope in craniofacial resection (CFR). This retrospective study was conducted at a single institution and included eight consecutive patients with head and neck tumors who underwent CFR between September 2019 and July 2021. During the transcranial approach, microsurgery was performed using an exoscope in the same manner as in traditional microscopic surgery, and an endoscope was used at the blind spot of the exoscope. The exoscope provided images of sufficient quality to perform microsurgery, while the sphenoid sinus lumen was the blind spot of the exoscope during anterior (n = 3) and anterolateral CFR (n = 2), and the medial aspect of the temporal bone was the blind spot of the exoscope during temporal bone resection (n = 2). These blind spots were visualized by the endoscope to facilitate accurate transection of the skull base. The advantages of the exoscope and endoscope include compact size, ergonomics, surgical field accessibility, and equal visual experience for neurosurgeons and head and neck surgeons, which enabled simultaneous transcranial and transfacial surgical procedures. All the surgeries were successful without any relevant complications. CEE is effective in transcranial skull base surgery, especially CFR involving simultaneous surgical procedures.

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 (

We present a case series of underwater microvascular decompression (MVD) for hemifacial spasm (HFS) and an evaluation of its feasibility and safety. This retrospective study was conducted at a single institution and included 20 patients with HFS who underwent underwater MVD between September 2019 and January 2021. Surgery was performed in 3 steps, as follows: exoscopic wound opening (soft tissue, bone, dura, and arachnoid around the cerebellomedullary cistern), underwater endoscopic surgery (decompression of the facial nerve), and exoscopic wound closure. In underwater endoscopic surgery, the surgical field was continuously irrigated with artificial cerebrospinal fluid. Abnormal muscle response and brainstem auditory evoked potentials (BAEPs) were monitored. Neurovascular conflicts were clearly observed in all patients without fogging and soiling of the endoscope lens. HFS was completely relieved in 19 patients (95%). An amplitude reduction of wave V of BAEPs of more than 50% was not observed in any of the cases. In 5 cases (25%), the latency of wave V of BAEPs was prolonged for more than 1.0 ms; these changes completely or near completely returned to baseline values at dural closure in all 5 cases. A postoperative complication of transient facial palsy was observed in 1 patient (5%) during postoperative days 10–30. There were no other complications. Our findings suggest that underwater MVD is a safe and feasible option for the treatment of HFS. However, it did not show advantages over conventional endoscopic MVD when the protective effect on the eighth cranial nerve was evaluated.

Chronic subdural hematoma (CSDH) is an angiogenic disease that is involved with many inflammatory mediators. Tie2 is predominantly expressed in the embryonic endothelium and plays an important role in the maturation and stabilization of the vasculature. Angiopoietin (Ang)1 and Ang2 are well-known ligands of the Tie2 receptor. We examined the expression of Ang1 and Ang2 in CSDH fluid and the expression of Tie-2 receptor and components of the angiogenic signaling pathways in the outer membrane of CSDH. Twenty-five samples of CSDH fluid and eight samples of outer membrane of CSDH were included. The concentrations of Ang1 and Ang2 in the CSDH fluid were measured using enzyme-linked immunosorbent assay (ELISA) kits. The expression of Tie2, phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) mechanistic target of rapamycin (mTOR), GβL, 70 kDa ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E (eIF-4E), and β-actin was examined by a Western blot analysis. The expression of Tie2, Akt, and mTOR was also examined by immunohistochemistry. The concentration of Ang2 in CSDH fluid was significantly higher than that in the serum or cerebrospinal fluid (CSF), and also higher than that of Ang1 in CSDH fluid. Tie2, PI3K, Akt, mTOR, GβL, p70S6K, and eIF-4E were detected in all cases. In addition, Tie2, Akt, and mTOR were localized in the endothelial cells of vessels in the CSDH outer membrane. Our data suggest that Ang2, although not Ang1, in CSDH fluid promotes angiogenesis in endothelial cells through the Tie2 receptor. The Ang2/Tie2 signaling pathway might therefore be a useful therapeutic target for treating the growth of intractable CSDH.

Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n = 229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with outcome. The time course of C5a levels was measured in plasma (n = 31) and CSF (n = 10). In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n = 15 per group). Brain sections from aneurysmal SAH patients showed increased presence of complement components C1q and C3/C3b/iC3B compared to controls. The complement component 5 (C5) SNP correlated with C5a plasma levels and poor disease outcome. Serial measurements in CSF revealed that C5a was > 1400-fold increased 1 day after aneurysmal SAH and then gradually decreased. C5a in plasma was 2-fold increased at days 3–10 after aneurysmal SAH. In the SAH mouse model, we observed a ≈ 40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH.

Objective The purpose of this study was to determine the sensitivity and specificity of using the spinal midline (M line) on a radiographic anteroposterior (AP) view for detecting pedicle screws (PSs) breaching the medial pedicle wall. Methods We retrospectively reviewed 145 patients who underwent fusion surgery using PSs between January 2006 and May 2017. We defined the M line as a line that connected the upper and lower spinous processes through the fixed vertebrae. The M line was positive if the tip of the PS crossed the M line. The reference standard was a computed tomography scan. The reliability of the M line was examined. Results The subjects included 145 patients (70 men and 75 women; mean age, 63.4 years). A total of 599 PSs were examined. Most cases were because of spondylolisthesis (66.9%). Most screws were inserted at a lower lumber level (77.6%). Analysis of the diagnostic accuracy of the M line yielded a sensitivity of 74.1% and a specificity of 95.3%. In addition, the positive predictive value of the M line was 42.6%, and the negative predictive value of the M line was 98.7%. Conclusions Assessment of the M line via an intraoperative radiographic AP view is a simple, readily available, complementary method for detecting PSs that have breached the medial pedicle wall in the thoracic, lumbar, and sacral spine. In particular, the M line has a strong negative predictive value, which is much more meaningful.

Objective Neutrophils induce inflammation through the exocytosis of cytotoxic granule proteins. Recently, neutrophils have been reported to be an independent parameter associated with unfavorable outcomes after subarachnoid hemorrhage (SAH). However, the mechanism by which neutrophils accumulate within the CSF after SAH remains undetermined. Methods Concentrations of C5a, epithelial neutrophil activating peptide 78 (ENA-78), interleukin-8 (IL-8), growth-regulated oncogene-α (GRO-α), neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO) were measured serially until day 14 in the CSF of 10 patients with SAH. CSF samples obtained from patients suffering from unruptured aneurysms were used as controls. Results The concentrations of C5a and ENA-78 were significantly increased on day 1, while those of IL-8 and GRO-α significantly increased during days 3–7 compared with those of the control samples. The levels of NGAL and MPO, components of neutrophil granules, significantly increased during days 1–5 and days 1–3, respectively, after SAH and gradually decreased thereafter. The correlations between ENA-78 and C5a on day 1, IL-8 and GRO-α on days 3–7, and NGAL and MPO on days 1–3 were significant. Conclusion These neutrophil chemoattractants might be serially involved in the infiltration of neutrophils into the CSF after SAH. Migrated neutrophils play an important role in inflammatory reactions in the central nervous system after SAH.

Objective To review the authors' surgical experience with radical temporal bone resection (TBR) with an emphasis on the classification of skull base osteotomy and transcranial tympanotomy (TCT) that is required for middle ear transection. Methods We reviewed the records of 25 patients who underwent radical TBR at our facilities between 2011 and 2020. Results The osteotomy line of radical TBR was divided into 3 segments: anterior (A), medial (M), and posterior (P). Each segment was further classified as follows: A1, through the glenoid fossa (1 patient); A2, in front of the glenoid fossa (23 patients); A3, through the greater wing of the sphenoid bone (1 patient); M1, through the middle ear (16 patients); M2, through the inner ear (9 patients); P1, through the mastoid (9 patients); and P2, through the posterior cranial fossa (16 patients). The M segment was significantly associated with operation time and intraoperative blood loss. In all patients with M1 osteotomy, TCT was performed; TCT was classified into superior and far posterior approaches. A superior approach was performed in all 16 patients, whereas the far posterior approach was performed in only 7 patients with both M1 and P2 osteotomy. Conclusions Our newly proposed osteotomy classification of radical TBR is suitable for minute but clinically important adjustment of the osteotomy line. TCT is an indispensable technique for M1 osteotomy; our newly proposed classification expands our understanding of TCT and how to incorporate this technique into radical TBR.

Chronic subdural hematoma (CSDH) is fundamentally treatable, although it sometimes recurs. We observed, however, several cases of spontaneous resolution of CSDH outer membranes, even in a trabecular type of CSDH, after a trepanation surgical procedure. In this study, we examined the expression of molecules of the autophagy signaling pathway in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation were included in this study. By Western blot analysis, we examined the expression of mammalian target of rapamycin (mTOR); GβL; UNC-51-like kinase-1 (ULK1); Beclin-1; autophagy-related genes (Atg) 3, 5, 7, 12, 13, and 16L1β,α; the autophagy marker Light Chain3A/B (LC3A/B); and β-actin, which constitute the autophagy signaling pathway. The expression levels of Beclin-1, Atg12, and LC3A/B were also examined by immunohistochemistry. Almost all of these molecules could be detected in all samples. Beclin-1, Atg12, and LC3A/B were found to be localized in the endothelial cells of vessels and fibroblasts in CSDH. We detected molecules of the autophagy signaling pathway in CSDH outer membranes. Autophagy contributes to the tissue homeostatic process, maintaining cellular integrity by clearing debris. Our data suggest that autophagy might play an important role in the spontaneous resolution of CSDH. Therefore, these molecules may be novel therapeutic targets for the treatment of those with CSDH.

Eosinophils induce inflammation by releasing cytokines and cytotoxic granule proteins. Infiltration of eosinophilic granulocytes occurs in the outer membrane of chronic subdural hematomas (CSDHs). Eosinophils play an important role in the growth of CSDHs. However, the manner in which eosinophils accumulate within CSDH fluid remains undetermined. In the current study, we assessed the expression of eosinophil chemoattractants in CSDH fluids according to growth stage of CSDHs and examined the correlation between the two. CSDH fluids were obtained from 38 patients during trepanation surgery. Ecalectin, eotaxin-3, interleukin-5 (IL-5), and eosinophil-derived neurotoxin (EDN) concentrations were measured using enzyme-linked immunosorbent assay kits. For use as controls, serum samples were collected from 5 healthy adults, and cerebrospinal fluid (CSF) samples were collected from 5 adults with unruptured aneurysms. The percentage of eosinophils (%eosinophil) in CSDH fluids was calculated using Giemsa staining. Concentrations of ecalectin, eotaxin-3, IL-5, and EDN were nearly equivalent in serum and CSF samples; however, their concentrations were high in CSDH fluids. In particular, ecalectin and EDN levels in CSDH fluids were significantly higher than those in serum and CSF. Levels of eotaxin-3, IL-5, EDN, and %eosinophil were significantly higher in laminar type of CSDH, whereas that of ecalectin was not. The correlations between eotaxin-3 and IL-5, IL-5 and EDN, and EDN and %eosinophil were statistically significant (p 0.01). Our data suggest that eotaxin-3 is a chemoattractant of eosinophils. IL-5 induces the activation of eosinophils subsequent to degranulation of EDN into CSDH fluids. These factors may serve as novel therapeutic targets for managing CSDH.

We previously demonstrated that the inflammatory cytokine interleukin-6 (IL-6) activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in fibroblasts within the outer membranes of chronic subdural hematomas (CSDHs), and the activation of this pathway may induce CSDH outer membrane growth. The inhibitory system for this signal transduction pathway is unknown. CSDH fluids were obtained from 10 patients during trepanation surgery as the case group, and cerebrospinal fluid (CSF) samples were obtained from seven patients suffering from subarachnoid hemorrhage (SAH) on Day 1 as the control group. The concentrations of IL-6, soluble IL-6 receptor (sIL-6R), and soluble gp130 (sgp130) in CSDH fluid and CSF were measured using enzyme immunoassay kits. The co-localization of IL-6 and sgp130 in CSDH fluid was examined by immunoprecipitation. The expression levels of STAT3, JAK2, suppressor of cytokine signaling 3 (SOCS3), and protein inhibitor of activated Stat3 (PIAS3) in the outer membranes of CSDHs were examined by immunostaining. Soluble IL-6R and sgp130 concentrations in CSDH fluid were significantly higher than those in CSF after SAH. Sgp130 and IL-6 were co-immunoprecipitated from CSDH fluid. Immunostaining revealed STAT3, JAK2, SOCS3, and PIAS3 expression in fibroblasts located in the outer membranes of CSDHs. Soluble gp130 binds to IL-6/sIL-6R and acts as an antagonist of the JAK/STAT signaling pathway. SOCS3 also binds to JAK and inhibits its signaling pathway. In addition, PIAS3 regulates STAT3 activation. These factors might down-regulate the IL-6/JAK/STAT signaling pathway in fibroblasts within CSDH outer membranes. Therefore, these molecules may be novel therapeutic targets for the inhibition of CSDH growth.

Background Ligamentum flavum (LF) hypertrophy is an important cause of lumbar spinal canal stenosis (LSS), one of the most common spinal disorders in the elderly. Although many cytokines are reported to be associated with LF hypertrophy, the intracellular signaling system is rarely discussed. The purpose of this study was to identify the JAK/STAT signaling pathway and to examine the role of the JAK/STAT systems in the hypertrophied LF. Methods The LF of 10 LSS patients was analyzed and the expression of JAK1, STAT3, phosphorylated ( p )-STAT3, and actin was examined by Western blot analysis. The expression of p -STAT3 was also examined by immunostaining and its positive cell ratio was compared between LSS and non-LSS samples. We measured the thickness of the LF on magnetic resonance images and studied the relationship between its thickness and the expression of p -STAT3. Results JAK1, STAT3, and p -STAT3 were detected in almost all samples by Western blot analysis. Immunoreactivity against p -STAT3 was observed mainly in endothelial- and fibroblast-like cells. The expression of p -STAT3 was significantly higher in LSS than non-LSS samples; it was significantly stronger on the dorsal than the dural side of the LF and positively correlated with the thickness of the LF on the dorsal side. Conclusions The JAK/STAT signaling pathway is positively correlated with the thickness of the LF. Our findings suggest that JAK1 and STAT3 molecules are involved in and regulate LF hypertrophy.

Objective This study investigated the diagnostic accuracy of the difference in the cross-sectional areas (CSAs) of affected cervical nerve roots (NRs) for diagnosing cervical radiculopathy (CR). Methods In total, 102 CR patients and 219 healthy volunteers were examined with ultrasound. The CSA of the cervical NR at each level was measured on the affected side and the contralateral side in CR patients by blinded ultrasonographic technicians. The difference between the CSAs of CR patients and normal volunteers and the difference in the laterality of CSA at the same affected level (ΔCSA) were calculated for each cervical level. Results The CSAs of the affected NRs in CR patients were significantly larger than those of the unaffected NRs in CR patients and those of the control group at the C5, C6 and C7 levels (P

Objective The resection of foramen magnum meningiomas (FMMs) presents neurosurgical challenges. We propose a simple classification of the tumor location and the operating space created by the tumor to help treatment planning. Methods We retrospectively analyzed 16 FMMs and divided them into 3 groups based on the tumor location—clival, foraminal, and atlantal tumors. The distance between the condyle and the neuraxis at the level of the foramen magnum was measured and defined as the available operative space (AOS). We also reviewed intraoperative video recordings to assess the surgical exposure of the tumor by the space created by the FMM and compared it with the AOS. Results There were 4 clival, 8 foraminal, and 4 atlantal tumors. The AOS of the clival tumors was 10 mm ± 1.7, the AOS of the foraminal tumors was 18 mm ± 3.7, and the AOS of the atlantal tumors was 12 mm ± 2.1. All foraminal and atlantal tumors could be detached without a brain retractor. Because a major portion of the clival tumors was covered by the spinomedullary junction, a brain spatula was needed to obtain the required surgical space. The difference in AOS between clival and foraminal/atlantal tumors was statistically significant (P = 0.044). Although 4 patients experienced postoperative complications, the average postoperative Karnofsky performance scale score improved. The surgical complication rate was significantly lower in foraminal and atlantal FMMs than in clival FMMs (P = 0.027). Conclusions The simple classification of the tumor location helped to assess surgical difficulties. Knowledge of the space created by the FMMs between the condyle and the neuraxis is useful for planning the approach strategy, especially for estimating the available working space without resection of the occipital condyle.

Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is highly abundant in the brain and exhibits broad substrate specificity, thereby it is thought to participate in the regulation of neuronal death and survival. Nitric oxide (NO), produced by neuronal NO synthase (nNOS), is an important neurotransmitter and plays a role in neuronal activity including learning and memory processes. However, high levels of NO can contribute to excitotoxicity following a stroke and neurodegenerative disease. Aside from NO, nNOS also generates superoxide which is involved in both cell injury and signaling. CaMKII is known to activate and translocate from the cytoplasm to the post-synaptic density in response to neuronal activation where nNOS is predominantly located. Phosphorylation of nNOS at Ser847 by CaMKII decreases NO generation and increases superoxide generation. Conversely, NO-induced S-nitrosylation of CaMKII at Cys6 is a prominent determinant of the CaMKII inhibition in ATP competitive fashion. Thus, the “cross-talk” between CaMKII and NO/superoxide may represent important signal transduction pathways in brain. In this review, we introduce the molecular mechanism of and pathophysiological role of mutual regulation between CaMKII and nNOS in neurons.

Chronic subdural hematoma (CSDH) is an angiogenic and inflammatory disease. Toll-like receptors (TLRs) transduce intracellular signals, resulting in the activation of nuclear factor κB (NF-κB), which leads to the production of inflammatory cytokines. High-mobility group box 1 (HMGB1) functions as a mediator of inflammatory responses through TLRs. In this study, we examined the expression of HMGB1 and components of the Toll-like receptor and NF-κB signaling pathways in the outer membrane of CSDH. Eight patients whose outer membrane was successfully obtained during trepanation surgery were included in this study. The expression of TLR4, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 4 (IRAK4), TNF receptor-associated factor 6 (TRAF6), TGFβ-activated kinase 1 (Tak1), interferon regulatory factors 3 (IRF3), IκB kinase β (IKKβ), IKKγ, IκBε, IκBα, NF-κB/p65 and β-actin was examined by Western blot analysis. The expression of TLR4, NF-κB/p65 and interleukin-6 (IL-6) was also examined by immunohistochemistry. The concentrations of HMGB1 and IL-6 in CSDH fluids were measured using ELISA kits. Above-mentioned molecules were detected in all cases. In addition, TLR4, NF-κB/p65 and IL-6 were localized in the endothelial cells of vessels within CSDH outer membranes. The concentrations of HMGB1 and IL-6 in CSDH fluids were significantly higher than that in the CSF and serum. There existed a correlation between the concentrations of HMGB1 and IL-6 in CSDH fluids. Our data suggest that HMGB1 in CSDH fluids produces the inflammatory cytokine IL-6 in endothelial cells through the Toll-like receptor and NF-κB signaling pathways. Anti-HMGB1 therapy might be a useful method to treat the growth of CSDH.

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.

Background Recently, various examination and intervention techniques using cervical nerve ultrasonography have been developed. The specific shapes of the C7 transverse process and vertebral artery in front of the C7 transverse process have become landmarks. Purpose To determine the prevalence of anomalies and anomalous vertebral artery entrances at the C7 transverse process. Material and Methods The records of patients who underwent plain or contrast-enhanced neck or cervical spine computed tomography (CT) were reviewed. The examinations were scored for the anomalous presence of anterior tubercles or cervical ribs as well as vertebral artery entrances in the C7 transverse process. The prevalence of anomalies was compared based on patient sex and age. Results Evaluating the examinations from 2067 patients (1046 men; 1021 women), 1% of patients exhibited an anomalous presence of anterior tubercles, and 0.3% of patients displayed cervical ribs at the C7 transverse process. The prevalence of anomalies process was significantly higher in men aged less than 40 years than in older men ( P Conclusion Although an anomalous vertebral artery entry into the C7 transverse foramen was rare, the prevalence of an anomaly at the C7 transverse process was higher in men aged less than 40 years. Therefore, we recommend performing CT in younger men before cervical nerve ultrasonographic intervention to avoid misinterpretations at the cervical level.

The medial branch of the posterior ramus of the lumbar spinal nerve is well known to be innervated independently and to end in the multifidus muscle without anastomosis. This prospective cohort study aimed to determine the diagnostic specificity and sensitivity of multifidus muscle denervation (MMD) by needle electromyography (N-EMG) for lumbar foraminal and lateral exit-zone stenosis (LF/LEZS). We enrolled 61 consecutive patients experiencing unilateral dysesthesia and/or leg pain in the L4 or L5 regions with suspicious LF/LEZS. The Japanese Orthopedic Association (JOA) score, Visual Analog Scale (VAS) for leg pain, and N-EMG were examined. In this study protocol, all patients received at least 3 months of conservative therapy. Surgery was performed on patients who experienced less than 50 % VAS pain relief compared with their initial score after confirming the responsible level by lumbar nerve root block. The specificity of N-EMG was the proportion of patients who improved with conservative therapies (non-surgery) after 3 months. The sensitivity of N-EMG was the proportion of patients who improved with surgical therapies (surgery) after more than 12 months. Twenty-three patients underwent surgery. The initial lower JOA, positive Kemp test and motor weakness were significantly higher in the surgery group. The MMD by N-EMG indicated that 34 of 38 patients were negative in the non-surgery group. In the surgery group, 21 of 23 patients were positive. The diagnostic sensitivity and specificity were 91.3 and 92.1 %, respectively. Needle electromyography is a simple and available additional method for the diagnosis of LF/LEZS.

Chronic subdural hematoma (CSDH) is fundamentally treatable through surgery, although CSDH recurs in some cases. We have observed several cases of spontaneous resolution of CSDH outer membranes, including in trabecular CSDH, after trepanation surgery. In this study, we examined the expression of molecules involved in caspase signaling in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation surgery were included in this study. The expression of Fas; Fas-associated death domain (FADD); tumor necrosis factor receptor type 1-associated death domain (TRADD); receptor-interacting protein (RIP); caspases 3, 7, 8, and 9; poly-(ADP-ribose) polymerase (PARP); DNA fragmentation factor 45 (DFF45) and β-actin was examined by Western blot analysis. The expression levels of PARP, caspase-3, and cleaved caspase-3 were also examined by immunohistochemistry. Fas; FADD; TRADD; RIP; caspases 3, 7, 8, and 9; PARP, and DFF45 were detected in nearly all samples. Caspase-3 and PARP were localized in the endothelial cells of vessels and in fibroblasts in CSDH outer membranes. In addition, cleaved caspase-3 was detected in fibroblasts. We detected molecules of the caspase signaling pathway in CSDH outer membranes. In particular, cleaved caspase-3 was detected, which suggests that apoptosis may occur within these membranes. Thus, during the growth of CSDH outer membranes, the caspase signaling pathway may be restrained. Once the pathway is activated, gradual resolution of CSDH outer membranes may occur. Therefore, these molecules may be novel therapeutic targets for intractable CSDH.

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).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 to3 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.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%.Plasmapore-coated titanium cages enabled more rapid solid bone fusion. We suggest that these types of cages might help to reduce postoperative radiograms.

We report a rare case of cervical radiculopathy associated with facet hypertrophy and disc herniation. The patient was a 38-year-old woman with sudden-onset left arm pain. As conservative therapy failed to alleviate her symptoms she was referred to us. On physical examination she manifested no neurological deficits except pain and dysesthesia in the left C7 territory. Computed tomography revealed hypertrophic ossified changes in the left T1 facet joint with encroachment on the spinal canal. Magnetic resonance imaging showed compression of the spinal cord at C6/7 by disc herniation at C6/7. Anterior cervical decompression and fusion by corpectomy (C7 corpectomy and C6/T1 fixation with a titanium cage) ameliorated her pain. Facet hypertrophy in a morphologically normal cervicothoracic spine is extremely rare and its etiology is unknown. We speculate the possibility that our patient harbored a congenital anomaly and that the morphologic changes were the consequence of an injury she sustained in a traffic accident.

In this paper the authors report the case of a patient with ossification of the posterior longitudinal ligament (OPLL) below the axial vertebra (C-2) at the kyphotic cervical spine, with an atlas vertebra (C-1) posterior arch that compressed the spinal cord with the head in a pathognomonic position, similar to a protruded position. This condition appears to be very rare. The morphological findings between the kyphotic cervical spine and OPLL, the upper occipitocervical junction, and the protruded-head position are discussed. A 40-year-old man presented with severe pain radiating to both legs when he yawned, sneezed, or extended his jaw (a protruded-head position). A kyphotic cervical spine with OPLL below C-2 was observed using CT and radiography, yet sagittal T2-weighted MRI failed to identify abnormal findings in a neutral or extension position, except for a slight cervical canal stenosis. However, in a pathognomonic protruded-head position, sagittal T2-weighted MRI showed a C-1 posterior arch that severely compressed the spinal cord at the upper cervical level. Therefore, the authors believe that the severe pain radiating to both legs was caused by a spinal canal stenosis due to a C-1 posterior arch impingement. The C-1 posterior arch was resected, and after the surgery, the patient indicated that the intolerable pain had disappeared. In conclusion, in patients with OPLL and a kyphotic cervical spine, the authors propose that the pathognomonic protruded position is valuable for estimating disrupted compensatory mechanisms at the upper cervical junction.

Chronic subdural hematoma (CSDH) is an inflammatory disease, the mechanism of which still remains to be elucidated. Interleukin-6 (IL-6), one of the inflammatory cytokines regulating janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, is expressed in human CSDH fluid. The status of this signaling pathway in human CSDH outer membranes was examined in the present study using outer membranes obtained during trepanation surgery. Concentrations of IL-6 in human CSDH fluids were measured using an enzyme immuno-assay kit. Expression patterns of JAK1, STAT1, phosphorylated (p)-STAT1 at Tyr(701) and at Ser(727), STAT3, p-STAT3 at Tyr(705) and at Ser(727) and actin in outer membranes were examined by Western blot analysis and immunohistochemistry. IL-6 is significantly expressed in human CSDH fluids compared with control cerebrospinal fluid. JAK1, STAT1 and STAT3 were detected in all cases. The expression of p-STAT3 at Tyr(705) is more significant compared with that of p-STAT1 at Tyr(701). In some cases, p-STAT3 at Ser(727) could also be detected, while p-STAT1 at Ser(727) could not. The localizations of STAT1 and STAT3 were revealed to be present in fibroblasts in human CSDH outer membranes, especially when p-STAT3 at Tyr(705) was in the nuclei of fibroblasts. These findings suggest that JAK1-STAT3 signaling is dominantly activated in fibroblasts of human CSDH outer membranes compared with STAT1 and indicate the possibility that this JAK1-STAT3 pathway might be activated by IL-6 and play a critical role in progression of human CSDH.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0675-7) contains supplementary material, which is available to authorized users.

Objective Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Interleukin-6, a well-known inflammatory cytokine, activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We previously reported that the JAK/STAT pathway is activated in fibroblasts in the outer membrane of CSDH. More recently, signal transducer and activator of transcription 3 (STAT3) has been shown to have a role in angiogenesis. We examined the expression of STAT3 in endothelial cells in the outer membrane of CSDH. Methods This study included 7 patients whose outer membranes were successfully obtained during trephination surgery. The expression of STAT3 and phosphorylated STAT3 was examined by Western blot analysis and immunohistochemistry. We also examined whether CSDH fluid could activate STAT3 in cultured endothelial cells in vitro. Results STAT3 and phosphorylated STAT3 were detected in all cases. Immunostaining showed that STAT3 and phosphorylated STAT3 were expressed not only in fibroblasts but also in vascular endothelium. Expression of phosphorylated STAT3 in endothelial cells was significantly induced immediately after treatment of CSDH fluid in vitro. The activation of STAT3 was significantly inhibited by treatment with antibodies that were directed against interleukin-6; however, this was suppressed by antibodies that were directed against vascular endothelial growth factor, but not significantly. Conclusions Interleukin-6 might dominantly activate STAT3 in endothelial cells, which might have a central role in endothelial cell proliferation and angiogenesis of CSDH outer membranes.

Chronic subdural hematoma (CSDH) is an angiogenic disease that is recognized as a cause of treatable dementia with unknown pathogenesis. Vascular endothelial growth factor (VEGF), a potent growth factor regulating angiogenesis through the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, has been implicated in its etiology. The status of this signaling pathway in CSDH outer membranes was examined in the present study, using outer membranes obtained during trepanation surgery. Expressions of PI3-kinase, PKB-kinase, Akt, phosphorylated Akt at Ser(473) (p-Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial-cadherin (VE-cadherin), and actin were examined by Western blot analysis, together with their immunohistochemistry. PI3-kinase, Akt, eNOS, and VE-cadherin were detected in all cases. The magnitude of the expression of p-Akt varied among cases; however, the localization was revealed to be present in endothelial cells of vessels in CSDH outer membranes, together with VEGF and VE-cadherin detected in endothelial cells of vessels. These findings suggest that the PI3-kinase/Akt signaling is activated in CSDH outer membranes, and indicate the possibility that the PI3 kinase/Akt pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDH.

Background Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Nuclear factor-kappa B (NF-κB) induces the production of inflammatory cytokines and adhesion molecules, which play an essential role in angiogenesis and inflammation. Recently, the double-stranded RNA-activated protein kinase (PKR) was shown to directly interact with NF-κB subunits to influence its transcriptional activity. Objective To examine the expression of NF-κB signaling pathway components and PKR in CSDH outer membranes. Methods Eight patients whose outer membranes were successfully obtained during trepanation surgery were included in this study. The IκBα, IKKβ, IKKγ, NF-κB, phosphorylated ( p )-NF-κB, and PKR expression levels were examined using western blotting analysis. NF-κB expression was also examined using immunohistochemistry. We investigated whether CSDH fluid could activate NF-κB in cultured endothelial cells in Vitro. Results The IκBα, IKKβ, IKKγ, and NF-κB levels were approximately the same. Additionally, p -NF-κB and PKR were detected at similar levels. Immunostaining showed that NF-κB was expressed in the vascular endothelium. p -NF-κB expression in endothelial cells was significantly induced immediately after treatment with CSDH fluid. Furthermore, NF-κB activation was significantly inhibited by treatment with antibodies directed against vascular endothelial growth factor. Conclusion PKR might activate NF-κB through vascular endothelial growth factor in endothelial cells, which might be associated with endothelial cell proliferation in the CSDH outer membrane. Thus, the NF-κB signaling pathway could play a critical role in CSDH growth.

BACKGROUND CONTEXT: Previous conventional magnetic resonance imaging reports on extraforaminal entrapment (e-FE) on L5–S1 have been problematic because of their complexity or lack of sensitivity and specificity. In this study, we propose a simple diagnostic method for e-FE. PURPOSE: The purpose of this study was to determine the sensitivity and specificity of using the difference in the foraminal spinal nerve (FSN) angle of the L5 nerve, as determined by oblique coronal T2-weighted imaging (OC-T2WI), for diagnosing L5–S1 unilateral e-FE. STUDY DESIGN: The study design involves diagnostic accuracy with retrospective case-control study. PATIENT SAMPLE: Seventy consecutive patients with unilateral L5 radiculopathy who underwent unilateral L5–S1 extraspinal canal decompression for e-FE or 4/5 intraspinal canal decompression for lumbar spinal canal stenosis between 2009 and 2013 were included. OUTCOME MEASURES: The Japanese Orthopedic Association score, Visual Analog Scale score for leg pain, and OC-T2WI for the FSN angle of the L5 nerve were examined. METHODS: The 70 patients were divided into two groups: Group A (n521) with unilateral L5– S1 e-FE and Group B (n549) with intraspinal canal L4–L5. Group C (n544) comprised the control group, which included only patients with back pain without leg radiculopathy. All patients underwent OC-T2WI, and the differences in the FSN angle of the fifth lumbar spinal nerve between the symptomatic and asymptomatic sides (DFSN angle) were examined and compared among the groups. RESULTS: There were no significant differences in the patient characteristics among the three groups. The DFSN angle was 17 � in Group A, 4.8 � in Group B, and 6.4 � in Group C, and the laterality was significantly larger in Group A than in the other two groups. A receiver-operating characteristic curve showed areas under the curve between groups A and B and between groups A and C of 0.93 and 0.97, respectively. In addition, the cutoff value of the DFSN angle (10 � ) indicated diagnostic accuracies of 94% and 91% (sensitivity and specificity) and of 93% and 95%, respectively. CONCLUSIONS: Determining differences in the FSN angle between the symptomatic and asymptomatic sides of greater than 10 � via OC-T2WI represented a simple, readily

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. Electronic supplementary material The online version of this article (doi:10.1186/s12974-014-0142-2) contains supplementary material, which is available to authorized users.

STUDY DESIGN A prospective study. OBJECTIVE To examine the diameter (mm), transverse diameter (mm), and cross-sectional area (mm²) of the C5, C6, and C7 nerve roots using ultrasonography. SUMMARY OF BACKGROUND DATA Each of the cervical nerve roots affected a different motor or sensory area. Although there were several studies that performed a detailed assessment of cervical nerve root anatomy in cadavers, only a few studies on the thickness of cervical nerve roots in living specimens have been performed. We examined whether the thickness of the C5, C6, and C7 nerve roots, as well as the area supplied by each of the roots, varied. METHODS All 219 subjects (99 males and 120 females; mean age, 47 ± 15 yr) were healthy volunteers. The diameter and the transverse diameter were measured via ultrasonography, and the cross-sectional area was calculated for each of the C5-C7 nerve roots. RESULTS The following diameter measurements (right and left, respectively) were obtained: C5, 2.8 and 2.9 mm; C6, 3.6 and 3.8 mm; and C7, 3.3 and 3.4 mm. The following transverse diameter measurements were obtained (right and left, respectively): C5, 2.8 and 3.0 mm; C6, 3.7 and 3.8 mm; and C7, 3.5 and 3.4 mm. The following cross-sectional area measurements (right and left, respectively) were obtained: C5, 6.3 and 6.4 mm²; C6, 10.7 and 11.0 mm²; and C7, 8.8 and 8.8 mm². Based on the 3 measurement methods, the C5 nerve root was significantly thinner than the other 2 nerve roots (P < 0.001), and the C7 nerve root was smaller than the C6 nerve root (P = 0.001). CONCLUSION The C5 nerve root was significantly thinner than the C6 and C7 cervical nerve roots. The fact that the C5 nerve is thinner may render it more susceptible to damage during cervical surgery.

Chronic subdural hematoma (CSDH) is considered to be an inflammatory disease. Eosinophils are frequently expressed in the outer membrane of CSDH and are major sources of transforming growth factor beta (TGF-β). The mothers against decapentaplegic (Smad)-signaling pathway, which is activated by TGF-β, has been shown to be involved with fibrosis. In the present study, we compared the concentrations of eotaxin-3, eosinophil-specific chemoattractant, and TGF-β between CSDH fluid and cerebrospinal fluid (CSF) from control patients. We also explored the expression of the Smad-signaling pathway in the outer membrane of CSDH. Eight patients whose outer membrane and 12 whose CSDH fluid were successfully obtained during trepanation surgery were included in the study. Concentrations of eotaxin-3 and TGF-β were measured by enzyme immunoassay kits. Expression levels of Smad2, phosphorylated Smad3, Smad3, Smad4, and actin were examined by Western blot analysis. In addition, expression of Smad3 was also examined by immunohistochemistry. Concentrations of eotaxin-3 and TGF-β in CSDH fluid were significantly higher than those in CSF. Smad2, Smad3, phosphorylated Smad3, and Smad4 were detected in all cases. Smad3 was shown to be present in fibroblasts. These findings indicate that eotaxin-3 is expressed in CSDH fluid, inducing eosinophils into the outer membrane and resulting in elevation of TGF-β with the Smad pathway activated by TGF-β. These data suggest a potential mechanism for CSDH formation and growth.

The inflammatory cytokine interleukin-6 (IL-6) plays an important role in causing symptoms of lumbar disk herniation. The present study clarifies the expression of the signaling pathway of IL-6 in herniated discs. Homogenates prepared from lumbar herniated discs from 10 patients were assessed. The expression of janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphorylated (p)-STAT3 at Tyr(705), suppressor of cytokine signaling 3 (SOCS3) and actin was examined by Western blot analysis. The expression of JAK1, STAT3, and p-STAT3 at Tyr(705) was also examined by immunostaining. JAK1, STAT3, p-STAT3 at Tyr(705) and SOCS3 were detected in almost all cases. Immunoreactivity against JAK1 and STAT3 was observed mainly in chondrocytes, whereas immunoreactivity against p-STAT3 at Tyr(705) was observed in the nuclei of chondrocytes. The JAK/STAT signaling pathway might be activated by IL-6 and transmit messages from the cell surface to the nucleus, and the pathway is negatively regulated by SOCS3. These JAK1, STAT3 and SOCS3 molecules might tightly regulate and play a role in the degeneration of chondrocytes within herniated discs.

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. Mehods 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.

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.

We report a case of multiple communicating intradural cystic lesions. Magnetic resonance imaging did not demonstrate the lesions. Neuroradiological diagnosis of the intradural arachnoid cysts was made from myelography and myelo-computed tomography using both lumbar and cervical punctures. These procedures give us useful information about flow dynamics in the spinal subarachnoid space.

The purpose of this study is to compare intervertebral bone fusion and clinical outcomes in L4-5 posterior lumbar interbody fusion (PLIF) using the same posterior instrumentation with four combinations of one of three types of interbody cage with one of two bone grafts, iliac and local or only local. In 67 patients who underwent L4-5 PLIF, 19 patients had the Brantigan cage and iliac and local bone graft, 18 with the TELAMON C cage and iliac and local bone graft, 16 with the TELAMON C cage and local bone graft (TL), and 14 with the OIC PEEK cage and local bone graft. Clinical assessments were based on Japanese Orthopaedic Association (JOA) scores and on the visual analogue scale (VAS). The bone fusion assessments were based on radiography and CT scans according to the Brantigan, Steffee, and Fraser criteria. More than 2 years after surgery, these assessments were made. In the results, the fusion outcome for the group receiving TL was significantly less than those for the other three groups. In TL, multivariate logistic regression analysis showed that the inside volume of the cage of ≥2.0 mL was the only significant factor for incomplete fusion. Moreover, the VAS (low back pain) score was significantly higher for TL than for the other three groups. In conclusions, we believe that the large volume inside the cage (≥2.0 mL) with local bone graft may lead incomplete interbody bone fusion and residual postsurgical low back pain after PLIF.

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.

Various surgical procedures have been used to repair disc herniations and osteophytes at the cervicothoracic junction. Among these procedures, transvertebral anterior foraminotomy without fusion is a relatively less invasive, safe and useful method, although the majority of spinal surgeons remain unfamiliar with this method. We describe the surgical procedure for a transvertebral anterior keyhole foraminotomy without fusion at the cervicothoracic junction, and we assess the middle-term clinical and radiological outcomes.Of 118 patients undergoing this surgery in our institute between 2007 and 2010, five (4.2 %) had C8 radiculopathy causing C7/T1 disc herniations or osteophytes. We studied five patients who underwent trans-C7 vertebral keyhole foraminotomy without fusion. We retrospectively examined clinical data, pre- and postoperative neurological status.In all cases, surgical decompression was successfully achieved without difficulty when accessing the pathology. No complications related to the surgical procedure were reported. The follow-up period was 12-28 (mean 20) months. In all patients, the visual analogue scale (VAS) due to radicular pain immediately decreased after the operation and did not increase thereafter. The mean VAS decreased from 7.8 (4.5-9.6) to 1.0 (0-2.1). The Cobb angle at C2-T1 in a neutral position improved from -12.6 (-2.8 to -24.7) degrees to -6.9 (4.2 to -25.4). The postoperative C7/T1 disc height decreased from 5.4 to 4.9 mm, indicating minimal loss.This procedure allows for direct access to the pathology and is less invasive. In this study, we clarified that this technique yields excellent radiological and clinical outcomes.

A spontaneous cervical epidural hematoma (SCEH) is a rare condition, which usually requires urgent treatment. However, unusual manifestations, such as hemiparesis, may lead to a misdiagnosis. We herein report a case of SCEH that presented with pure motor hemiparesis to discuss the appropriate and prompt diagnosis and treatment of such cases. An 84-year-old female was brought to our emergency department complaining of nuchal pain, followed by right hemiparesis. A contrast-enhanced computed tomography (CT) scan of the neck demonstrated a spinal epidural hematoma right posterolateral to the spinal cord, extending from C2 to C3. She was managed conservatively and her symptoms improved significantly. The authors emphasize that cervical spinal lesions should be considered in the differential diagnosis for patients with acute onset of hemiparesis, when they are associated with neck pain. Even though magnetic resonance imaging is the gold standard, a CT scan is also useful for quick screening for SCEH. Key words: spinal epidural hematoma, hemiparesis, cerebrovascular stroke, diagnosis, spontaneous remission

There are mainly two surgical methods for lumbar foraminal stenosis, simple decompression of the extra-foraminal portion or decompression with fixation surgery. However the indication of either method is controversial. The aim of this study is to show our surgical method and results.In six cases diagnosed as lumbar foraminal stenosis with or without far lateral disc herniation by X-ray, CTscan, MRI and nerve conduction velocity, decompression surgery was performed by our paramedian method (Wiltse approach). The apex and lateral portion of the superior articular facet (one third to one fourth) and the transforaminal ligament without fixation for lumbar foraminal stenosis. All patients were followed up for more than 10 months after the surgery. Japanese Orthopaedic Association (JOA) score and Visual Analogue Scale (VAS) were assessed before surgery and more than 10 months after the surgery. Postoperative radiological assessments were examined by neutral, flexion and extension X-ray.Foraminal stenosis was successfully decompressed in all cases. The postoperative JOA score and VAS were significantly improved in comparison to the preoperative score (Recovery Rate ware of 74.9% and 85.8%). There was no recurrence of symptoms or necessity for secondary surgery. The radiological evaluation did not indicate significant instability or decrease in the disc height.Our surgical method, removing the apex and lateral part of the superior articular process and transforaminal ligament without fusion led to a good outcome and recurrence 10 months after the surgery had not occurred.

Adiponectin is produced from fatty tissue and has been reported to be involved with metabolic syndrome. Recently, adiponectin has been demonstrated to play a neuroprotective role against cerebral ischemia. In this study, we explored the time-course serial expression changes of adiponectin in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH) and the effects of adiponectin on cerebral arteries. The concentrations of adiponectin were measured serially until day 14 in CSF of 8 patients with SAH. The CSF samples obtained from 6 patients suffering from an unruptured aneurysm were used as controls. Serum samples were collected from 6 healthy adult volunteers. Rat cerebral arteries were incubated with adiponectin (2μg/ml). Western blot analysis using AMP-activated protein kinase α (AMPKα), phosphorylated (p)-AMPKα at Thr(172), endothelial nitric oxide synthase (eNOS), p-eNOS at Ser(1177) and actin antibodies was then performed. The adiponectin concentrations in serum and control CSF were 17,670±3748ng/ml and 9.2±3.0ng/ml, respectively. After SAH, the concentration of adiponectin in the CSF significantly increased on the first post-SAH day and gradually decreased thereafter. Adiponectin significantly phosphorylated both the AMPKα and eNOS of the cerebral arteries. Our findings suggest that adiponectin is significantly increased in the CSF after SAH, resulting in the activation of AMPKα and eNOS. Adiponectin plays an important role against cerebral vasospasm via the AMPK/eNOS signaling pathway.

Many modifications to trapeziectomy have been proposed for the treatment of thumb basal joint arthritis. Their final outcomes have been discussed intensively, whereas functional changes in the early post-operative period have not been fully documented. The purpose of the present study is to evaluate an early functional change following our modified ligament reconstruction with tendon interposition (LRTI) arthroplasty. Nine patients (ten thumbs) were included in this study. Pain levels, strength, and mobility were assessed before and after surgery at intervals of two months. Pain level significantly improved at two months after surgery. Grip and pinch strengths had increased gradually after a temporal decrease at two-month follow-up, and were significantly stronger at six months after surgery. Palmar abduction improved significantly at six months after surgery, whereas opposition did not change significantly. A modified LRTI is an effective procedure in terms of early functional improvement of pain, strength, and mobility.

A 34-year-old man had a multiple arthralgia for about eleven months. The swelling of his right wrist and foot had appeared in the dorsal side, and he had been misdiagnosed as the rheumatoid arthritis. He was treated with prednisolone in the dosages of 2.5 mg per day for one month, and 10 mg per day for ten months. When he admitted to our hospital, the bone X-ray examinations of the wrist and foot revealed the marked atrophy and destruction of the carpal and tarsal bones. The aspiration fluid from the swelling around his wrist and foot was positive for acid-fast bacilli on smear and Mycobacterium tuberculosis was found on culture. He was treated with isoniazid, rifampicin, ethambutol and pyrazinamide, however, these medication was not adequately effective to his complications of tuberculous arthritis. Curettage, irrigation and synovectomy of his right carpal and tarsal bone were performed in order to control his bone and joint infection. He recovered from his arthritis and tenosynovitis after these operations. The clinical practitioners should not omit tuberculosis from the differential diagnosis of persistent osteoarthralgia.

Object. The authors report a simple method for bilateral open-door cervical expansive laminoplasty in which hydroxyapatite (HA) spacers are secured by titanium screws. A biomechanical study was also conducted to confirm the strength of the screw fixation. Methods. A unilateral posterior approach was used to allow preservation of the posterior supporting elements (the posterior tension band) until the laminae were cut at the base. A bilateral open-door expansive laminotomy was then performed in standard fashion. Appropriate-sized HA spacers were selected, held with a specially designed holder, and placed between the split laminae. The screw holes were made in the laminae along the direction of the screw holes in the spacer, and two screws were inserted ventrolaterally to the laminae, resulting in instantaneous fixation. This procedure was performed in 15 patients; clinical results were successful, and there were no significant intraoperative complications. Follow-up radiological studies revealed no evidence of displacement of the spacers or screw backout. The screw artifacts observed on magnetic resonance imaging were minimal, allowing evaluation of the cervical spinal cord. The sagittal alignment of the cervical spine was well preserved. In the biomechanical studies the authors found that the screw fixation was of satisfactory strength, compared with other methods of fixation. Conclusions. Bilateral open-door cervical expansive laminoplasty in which HA spacers are secured by titanium screws is a simple and quick method that yields sufficient fixation strength.

OBJECTIVE: To investigate nitric oxide (NO) metabolism after subarachnoid hemorrhage (SAH). METHODS: We measured the concentrations of the NO metabolites, nitrite and nitrate, in cerebrospinal fluid (CSF) obtained from the cisternal drainage of patients with SAH. Studies were performed for 31 patients who had undergone surgical obliteration of bleeding aneurysms within 3 days of their hemorrhage. The concentrations of nitrite and nitrate in the CSF were measured for 14 days using a nitrate/nitrite kit and samples that were obtained on a daily basis from the cisternal drainage. RESULTS: Compared with the control values in the CSF (2.6 ± 0.4 μmol/L, n = 14) obtained from patients with hemifacial spasm, trigeminal neuralgia, or nonruptured aneurysms, the concentrations of nitrite and nitrate in the CSF were significantly elevated in the acute stage of SAH and remained elevated. The concentration of NO metabolites may correlate with the amount of bleeding, inasmuch as the values in patients in Fisher Group 3 (n = 25) were higher than those in patients in Fisher Group 2 (n = 6). The concentration of nitrate was higher than that of nitrite, suggesting that NO in the subarachnoid space is mainly absorbed by hemoglobin and degraded to nitrate. No differences were demonstrated in patients treated with high doses of methylprednisolone (n = 17) compared with those treated with usual-dose steroids (n = 14). Steroids are known to prevent the formation of inducible NO synthase mediated by inflammatory cytokines. CONCLUSION: NO metabolism in the brain is stimulated after SAH. Nitrate is the dominant NO metabolite in CSF after SAH. The involvement of inducible NO synthase in the pathophysiology of NO metabolism after SAH was not clearly suggested based on the present data.

The intravenous infusion of rat adrenomedullin, at concentrations ranging from 0.1 to 1.0 μg/kg/min, for 60 min increased the regional cerebral blood flow (rCBF) in a dose-dependent manner in rats. rCBF was measured using a laser Doppler flowmetry device placed on the surface of the parietal cortex. The increase in rCBF induced by 1.0 μg/kg/min of adrenomedullin was up to 145 ± 10.8% of controls at 60 min (n = 5, p < 0.001). These concentrations of adrenomedullin did not affect systemic blood pressure or other physiologic parameters, including pH, PaCO2, PaO2, hemoglobin, and blood glucose. Repeated infusion of 1.0 μg/kg/min of adrenomedullin at 2-h intervals caused tachyphylaxis (n = 5, p < 0.01). Rat adrenomedullin (1.0 μg/kg/min) demonstrated a more potent effect than the same dose of human adrenomedullin. The C-terminal fragment of human adrenomedullin (0.5 and 5.0 μg/kg/min), adrenomedullin22–52, which did not affect rCBF alone, inhibited the effect of rat adrenomedullin (0.5 μg/kg/min) as a receptor antagonist in a dose-dependent manner. In a model of middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats, pre- and postinfusion of 1.0 μg/kg/min of adrenomedullin suppressed the reduction in rCBF following MCA occlusion (control, 29 ± 15.1%; adrenomedullin group, 45 ± 14.4%; not significant) and decreased the volume of ischemic brain injury (control, 288 ± 35 mm3; adrenomedullin group, 232 ± 35 mm3; p < 0.05). These results suggest that adrenomedullin increases rCBF and prevents ischemic brain injury, partly by increasing the collateral circulation.

Cytokine responses to surgical trauma have been studied in 70 patients undergoing various neurosurgical procedures. Serum concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8, (IL-8), tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured before and after surgery using enzyme-linked immunosorbent assays. The serum concentrations of IL-1 beta, IL-8, TNF-alpha, and IFN-gamma did not change significantly following neurosurgical operations. In contrast, serum IL-6 levels were significantly elevated following surgery, peaking at postoperative day 1 and then gradually decreasing. Maximum IL-6 concentrations were considerably higher in patients who underwent surgery for brain tumours or aneurysms as compared with patients who had a ventriculoperitoneal shunt, neurovascular decompression or transsphenoidal adenomectomy. Intra-operative use of methylprednisolone, which is known to block the production and action of cytokines, suppressed the increase in IL-6 levels after surgery. There was a statistically significant correlation between the IL-6 peak concentration and the length of surgery in patients not treated with steroids, but not in patients treated with steroids. Additionally patients who underwent supratentorial surgery had higher peak concentrations of IL-6 than those who underwent infratentorial surgery. These results suggest that IL-6 is an early marker of tissue damage and may be useful in assessing the extent of postoperative stress.

A rare case of true aneurysms of the middle meningeal artery (MMA) associated with cavernous hemangioma in a 47-year-old male is presented. Angiography showed aneurysmal dilatation of the MMA, which was a tumor feeder. Histological examination confirmed the true aneurysmal character of the dilatation. The aneurysms were considered to result from increased hemodynamic stress and medial defects in the MMA.