[Lumbar Interbody Fusion:How to Achieve Reliable Bone Fusion?]

The goal of surgery for degenerative spine disease is to decompress nerves; however, extensive spinal decompression may compromise spinal stability. Therefore, spinal fusion surgery is performed to immediately stabilize such anatomical disruption during a short hospital stay and to allow quick recuperation. Recently, implants such as pedicle screws and intervertebral cages have been regularly used in lumbar fusion surgery. These implants are used to reconstruct the functional unit of the failed spine, correcting any deformity if necessary and maintaining its fixation until complete bone fusion. In other words, the essence of spinal fusion surgery is not the placement of implants but the induction of bone fusion. Therefore, each case requires a carefully developed surgical plan to achieve sufficient bone fusion for spinal stabilization. In this article, we describe the mechanism and the surgical technique for achieving reliable interbody fusion.

Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model.

BACKGROUND/AIMS: Bone marrow stromal cells (BMSCs) transplantation is an important strategy for the treatment of ischemic stroke. Currently, there are no effective methods to guide BMSCs toward the targeted site. In this study, we investigated the effect of electrical stimulation on BMSCs migration in an ischemic model of rats. METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. BMSCs (2.5×105 cells/ 4 µl PBS) were stereotaxically injected into the left corpus callosum at 1 day after MCAO. After BMSCs injection, a plate electrode with a diameter of 3 mm connected to an implantable electrical stimulator was placed on the right frontal epidural space and a counter electrode was placed in the extra-cranial space. Electrical stimulation at preset current (100 µA) and frequency (100 Hz) was performed for two weeks. Behavioral tests were performed at 1, 4, 8, and 15 days after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at 15 days after MCAO for evaluation of infarction area and the migration distance and area of BMSCs found in the brain tissue. After evaluating cell migration, we proceeded to explore the mechanisms guiding these observations. MCAO rats without BMSCs transplantation were stimulated with same current and frequency. At 1 and 2 weeks after MCAO, rats were euthanized to evaluate stromal cell-derived factor 1 alpha (SDF-1α) level of brain tissues in the bilateral cortex and striatum. RESULTS: Behavioral tests at 4, 8, and 15 days after MCAO revealed that stimulation group displayed significant amelioration in mNSS and cylinder test compared to control group (p<0.05). Similarly, the infarction areas of stroke rats in stimulation group were significantly decreased compared to control group (p<0.05). Migration distance and area of transplanted BMSCs were significantly longer and wider respectively in stimulation group. An increased concentration gradient of SDF-1α in stimulation group accompanied this enhanced migration of transplanted cells. CONCLUSIONS: These results suggest that electrical stimulation enhances migratory ability of transplanted BMSCs in ischemic stroke model of rats. If we can direct the implanted BMSCs to the site of interest, it may lead to a greater therapeutic effect.

Spinal Extradural Arachnoid Cyst: Significance of Intrathecal Infusion after Fistula Closure.

The spinal extradural arachnoid cyst is a rare entity. Obtaining the correct diagnosis and detecting the fistula location are critical for providing effective treatment. A 41-year-old man had numbness in the soles of his feet for 2 years with accompanying gait disturbance, and a defecation disorder. Computed tomography myelography performed at another hospital revealed an epidural arachnoid cyst from Th11 to L2. He received a subarachnoid-cyst shunt at the rostral part of the cyst. However, his symptoms worsened and he was admitted to our hospital. Neuroradiological investigations revealed the correct location of the fistula at the level of Th12. We performed partial removal of the cyst wall with fistula closure via right hemilaminectomy of Th11 and 12. The complete closure of the fistula was confirmed by intrathecal infusion of artificial cerebrospinal fluid through the shunt tube. The shunt tube was removed with the sutures. The patient's symptoms improved, although numbness remained in his bilateral heels. There has been no recurrence in 15 months since the surgery. Fistula closure may work as a balanced therapeutic strategy for spinal extradural arachnoid cyst, and intrathecal cerebrospinal fluid infusion is useful for the confirmation of complete fistula closure.

Mesenchymal Stem Cell Therapy for Ischemic Stroke.

　To date, many animal studies have indicated the neuroprotective effects of mesenchymal stem cell (MSC) transplantation in ischemic stroke. Several clinical studies have also revealed the safety, feasibility, and neuroprotective effects in ischemic stroke patients. In this review, we present the main approaches of MSC transplantation in ischemic stroke, the mechanisms of MSC therapy, and the current clinical studies on MSC transplantation in ischemic stroke patients. We also explore the safety of MSC transplantation and conclude that MSC therapy will play an important role in the future treatment of ischemic stroke. The optimal timing, approach, and cell dose in the transplantation are important issues for successful clinical application.

Surgery in the Standing Position by a Surgeon with Achilles Tendon Rupture.

Unexpected injuries can have a profound effect on a surgeon's performance and thus on patients and surgical departments. Here we describe a technique for performing surgery in the standing position, as done by a surgeon with an Achilles tendon rupture. During his prescribed 45-day non-weight-bearing period for the left ankle after surgery for an Achilles tendon rupture, the surgeon was able to participate in 15 surgeries as an operator or assistant, due to his use of a combination of injured-leg genuflection on a stool and a 'Surgical Body Support' device. Similarly injured surgeons may benefit from such support.

Neuroprotective effects of liraglutide for stroke model of rats.

The number of diabetes mellitus (DM) patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1) are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson's test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF). The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.

Regenerative medicine for epilepsy: from basic research to clinical application.

Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data.

[A case of a paraspinal arteriovenous fistula presenting with retroperitoneal hemorrhage treated by staged transarterial and transvenous embolization].

We report a rare case of a paraspinal arteriovenous fistula(AVF)treated by combined transarterial and transvenous embolization(TAE/TVE). A 72-year-old woman was admitted after a traffic accident. Abdominal enhanced CT disclosed pre-existing large varices at the L3-L4 level in the right retroperitoneum with multiple feeding arteries and veins draining into the extradural venous plexus in the spinal canal. The lesion was diagnosed as a paraspinal AVF. Four days later, the patient went into a state of shock. Emergency abdominal CT showed retroperitoneal hemorrhage due to rupture of the varix. TAE of the feeders from the right L1-L4 arteries was performed, and rebleeding from the varix was prevented. Three months later, follow-up CTA showed regrowth of the AVF, and TVE was performed. Two microcatheters were navigated transvenously into the varix, and detachable coils were delivered into the small compartment just downstream to the shunts, leading to complete obliteration. We conclude that transarterial flow reduction followed by occlusion of the venous side of the shunts is effective to achieve cure of a complex and high-flow paraspinal AVF.

[Antitumor effects of gefitinib for metastatic brain tumors from lung carcinomas with EGFR mutation].

OBJECTIVE: Patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutation respond remarkably well to tyrosine kinase inhibitors of the EGFR (EGFR-TKI). We examined the relation of the EGFR mutation and the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer. MATERIALS AND METHODS: Forty-one patients with brain metastases from lung cancer were treated in our hospital from January 2007 to October 2010. Among them, 9 patients were examined on their EGFR mutation of tumors using the PNA-LNA PCR clamp method, and were treated with gefitinib, given orally at a daily dose of 250 mg. The drug efficacy for brain tumors was evaluated with MRI and CT. RESULTS: Seven patients had EGFR mutation (4 in exon 19, and 3 in exon 21). Five patients showed partial response, 3 remained stable, and one had progressive disease. All 5 patients who showed partial response had EGFR mutation. One patient who had progressive disease had no EGFR mutation. Three patients (case 1, 2 and 6) among 5 patients who showed partial response were well controlled only with gefitinib (without radiation). CONCLUSION: This study suggests that the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer is related to the EGFR mutation of tumor.

Syringo-peritoneal Shunt for Syringomyelia Due to Extensive Adhesive Arachnoiditis: A Case Report.

Adhesive arachnoiditis (AA) is a chronic inflammation inside the dura and remains one of the most challenging diseases. We describe a case of treatment-resistant extensive AA that offers insight into surgical treatment selection. The patient had a 2-year history of progressive spastic gait and was diagnosed with syringomyelia caused by extensive AA. Although syringe-subarachnoid and subarachnoid-subarachnoid shunting resulted in recurrence within a short period, syringo- peritoneal shunting improved the symptoms and there was no recurrence. This case suggests that syringo-peritoneal cerebrospinal fluid (CSF) shunt drainage, which has previously been considered a further step, may be a first-surgery option for extensive AA.

A Case Report of Possible Thoracic Interdural Ganglion Cyst.

There are some intraspinal cystic lesions presenting with myelopathy. We report a case of myelopathy caused by a possible thoracic interdural ganglion cyst. A 70-year-old man with subacute bilateral lower extremity numbness, muscle weakness, and gait disturbance presented to our hospital. Magnetic resonance (MR) images showed a cystic lesion which compresses the left dorsolateral intraspinal space of T2-3. During surgery, a ganglion cyst was found without adhering to the periphery of the epidural space. The capsule and contents were removed. He showed postoperative improvement in activities of daily living. A postoperative pathological diagnosis of ganglion cyst was made. The development mechanism of thoracic interdural ganglion cysts is unknown. To our knowledge, this is the first report of this disease. Surgery improved symptoms of a patient with myelopathy caused by thoracic interdural ganglion cysts. This must be considered as one of the cystic lesions presenting with myelopathy.

Synovial Cyst of the Atlantoaxial Joint Removed through a Posterior Intradural Approach.

Introduction. Synovial cysts rarely develop in the atlantoaxial joint. We report a case of posterior C1-2 laminectomy for a synovial cyst of the atlantoaxial joint which passed through the dorsal dura and put pressure on the cervical spinal cord. Case Presentation. A 62-year-old man with rapid progression of pain and weakness in the left upper extremity presented to our hospital. A cervical spine X-ray showed left C5-6 and C6-7 stenoses. A cervical magnetic resonance imaging showed an intradural extramedullary cystic lesion on the right side of the ventral cervical spinal cord at the C1-2 level and severe compression of the cervical spinal cord. Because a cyst was partially enhancing, a tumor lesion was not identifiable. Due to severe spinal cord compression, we performed intradural cyst removal via a posterior intradural approach with C1-2 laminectomy and left-sided C5-6 and C6-7 foraminotomies. One year after surgery, the cyst did not recur, and atlantoaxial instability did not appear. Discussion. A compressive lesion on the cervical spinal cord was not identified preoperatively as a synovial cyst. However, intraoperative and pathological findings suggested that the compressive lesion can be a synovial cyst which passed through the dorsal dura. The surgical treatment strategy for a synovial cyst of the atlantoaxial joint is controversial due to factors, such as the presence of atlantoaxial instability, level of cyst causing compression of the cervical spinal cord, severity of myelopathy, and cyst location. In the present study, the cervical spinal cord was highly compressed and the cyst was located on the right side of the cervical spinal cord; we chose cyst removal through a posterior intradural approach with C1-2 laminectomy.

Long-Term Potentiation Enhances Neuronal Differentiation in the Chronic Hypoperfusion Model of Rats.

Several reports have shown that long-term potentiation (LTP) per se effectively enhances neurogenesis in the hippocampus of intact animals. If LTP can enhance neurogenesis in chronic hypoperfusion, this approach could potentially become a new therapeutic strategy for the restoration of cognitive function and for prevention from deterioration of mild cognitive impairment (MCI). Using an in vivo LTP model of rats, we examined whether LTP per se can enhance neurogenesis in hypoperfusion rats that underwent permanent bilateral common carotid artery occlusion (permanent 2-vessel occlusion, P2VO). High frequency stimulation (HFS) in the subacute phase after P2VO enhanced hippocampal cell proliferation and neurogenesis. However, most enhanced cell proliferation and neurogenesis was seen in the hypoperfusion rats that received HFS and for which LTP could finally be induced. In contrast, the same effect was not seen in the LTP induction in the chronic phase. The present findings, which reveal that most enhanced neurogenesis was seen in hypoperfusion rats for which LTP could be finally induced, could explain the ability of LTP-like activities such as learning paradigms and environmental stimuli to increase the rate of neurogenesis in the hippocampus even under hypoperfusion conditions. Moreover, the present findings, which reveal that LTP induction in the chronic phase after P2VO could not effectively enhance neurogenesis in the hypoperfusion rats, could indicate that patients with MCI and even middle-aged healthy control individuals should start LTP-like activities as early as possible and continue with these activities to prevent age-related deterioration of hippocampal function.

Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease.

The high mobility group box-1 (HMGB1) exists as an architectural nuclear protein in the normal state, but displays an inflammatory cytokine-like activity in the extracellular space under pathological condition. Inflammation in the pathogenesis of Parkinson's disease (PD) has been documented. In this study, we investigated the involvement of HMGB1 in the pathology and the neuroprotective effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on an animal model of PD. Adult female Sprague-Dawley rats were initially injected with 6-hydroxydopmaine (6-OHDA, 20 µg/4 µl) into the right striatum, then anti-HMGB1 mAb (1 mg/kg), or control mAb was intravenously administered immediately, at 6 and 24 h after 6-OHDA injection. The treatment with anti-HMGB1 mAb significantly preserved dopaminergic neurons in substantia nigra pars compacta and dopaminergic terminals inherent in the striatum, and attenuated PD behavioral symptoms compared to the control mAb-treated group. HMGB1 was retained in the nucleus of neurons and astrocytes by inhibiting the proinflammation-induced oxidative stress in the anti-HMGB1 mAb-treated group, whereas HMGB1 translocation was observed in neurons at 1 day and astrocytes at 7 days after 6-OHDA injection in the control mAb-treated group. Anti-HMGB1 mAb inhibited the activation of microglia, disruption of blood-brain-barrier (BBB), and the expression of inflammation cytokines such as IL-1ß and IL-6. These results suggested that HMGB1 released from neurons and astrocytes was at least partly involved in the mechanism and pathway of degeneration of dopaminergic neurons induced by 6-OHDA exposure. Intravenous administration of anti-HMGB1 mAb stands as a novel therapy for PD possibly acting through the suppression of neuroinflammation and the attenuation of disruption of BBB associated with the disease.

Intra-Arterial Transplantation of Allogeneic Mesenchymal Stem Cells Mounts Neuroprotective Effects in a Transient Ischemic Stroke Model in Rats: Analyses of Therapeutic Time Window and Its Mechanisms.

OBJECTIVE: Intra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase. METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1 × 10(6) cells/ 1 ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48 h group) after MCAO. PBS (1 ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays. RESULTS: Behavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p's<0.05). Similarly, the infarct volumes of stroke rats in 24h group were much significantly decreased compared to those in all other groups (p's<0.05). These observed behavioral and histological effects were accompanied by MSC survival and migration, with the highest number of integrated MSCs detected in the 24h group. Moreover, bFGF and SDF-1α levels of the infarcted cortex were highly elevated in the 24h group compared to control group (p's<0.05). CONCLUSIONS: These results suggest that intra-arterial allogeneic transplantation of MSCs provides post-stroke functional recovery and reduction of infarct volumes in ischemic stroke model of rats. The upregulation of bFGF and SDF-1α likely played a key mechanistic role in enabling MSC to afford functional effects in stroke. MSC transplantation at 24 hours after recanalization appears to be the optimal timing for ischemic stroke model, which should guide the design of clinical trials of cell transplantation for stroke patients.

Mannitol enhances therapeutic effects of intra-arterial transplantation of mesenchymal stem cells into the brain after traumatic brain injury.

Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major cause of death that affects a broad range of ages. The aim of this study was to investigate the therapeutic effects of intra-arterial transplantation of mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol (25%) in a TBI model of rats. TBI models were produced with a fluid percussion device. At 24h after TBI, MSCs (1×10(6)cells/100µl) with glycerol or mannitol were administered via the right internal carotid artery. Rats were evaluated behaviorally and immunohistochemically, and hyperpermeability of the blood-brain barrier (BBB) induced by hypertonic solutions was explored. Compared to PBS or glycerol, the administration of mannitol resulted in increased BBB disruption. The mannitol-treated rats showed significant improvement in motor function. Intra-arterial transplantation of MSCs caused no thromboembolic ischemia. Immunohistochemically, more MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24h after transplantation. Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. This technique might be used for patients with diseases of the central nervous system including TBI.