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Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population., Koda et al. present the results of a randomized phase 3 trial comparing granulocyte colony-stimulating factor versus placebo in patients with acute spinal cord injury. While the primary endpoint was not met, a sub-analysis revealed a trend towards superior efficacy of G-CSF versus placebo in an elderly population.

Highlights • Neurofibromatosis type 1 (NF-1) is often associated with various orthopedic disorders, especially scoliosis. • Spinal deformity in patients with NF-1 can be induced by localized neurofibromas. • The optimum surgical approach for the release of neurofibroma located in the posterior mediastinal remains to be established. • We safety performed a two-stage procedure involving the release of a neurofibroma in the lateral position/extirpation of the neurofibroma and posterior spinal fusion with segmental spinal instrumentation for scoliosis in the prone position., Background Neurofibromatosis type 1 (NF-1) is often associated with various orthopedic disorders, especially scoliosis. Spinal deformity in patients with NF-1 can be induced by localized neurofibromas. Case presentation Scoliosis can be induced by a localized neurofibroma. A 12-year-old boy diagnosed with neurofibromatosis type 1 had severe scoliosis caused by a neurofibroma located in the posterior mediastinum. We performed two-stage procedure involving the extirpation of the neurofibroma in the lateral position, and posterior spinal fusion with segmental spinal instrumentation for the scoliosis in the prone position. Discussion The optimum surgical approach for the extirpation of neurofibroma located in the posterior mediastinal remains to be established. It may be difficult to extirpate a tumor in this position via a posterior approach alone, as the tumor is surrounded by several tissue, e.g. azygos vein, trachea and esophagus. In our case, we first extirpated the tumor located in the posterior mediastinum via a posterolateral incision in the right lateral position. With this approach, it may be easy to confirm the safe relationship between the tumor and surrounding tissue. Conclusions We safely performed a two-stage procedure involving the extirpation of a neurofibroma in the lateral position, and posterior spinal fusion with segmental spinal instrumentation for scoliosis in the prone position.

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m 2 /day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752.

金沢大学附属病院神経内科, We report two cases of superficial siderosis (SS) of the central nervous system (CNS), which is caused by chronic haemorrhaging into the subarachnoid space with haemosiderin deposition in the superficial portion of the CNS. Patient 1 had fluid collection in the spinal canal, which was reported as the source of the chronic bleeding. Patient 2 was bleeding from thickened dura at the level of the sacral vertebrae. Both of the patients had xanthochromic cerebrospinal fluid. We surgically repaired the sources of bleeding. Subsequently the cerebrospinal fluid (CSF) cleared and their symptoms were not aggravated for about 1 year. We measured several CSF markers of SS before and after surgery. Total tau protein (CSF-t-tau), phosphorylated tau protein (CSF-p-tau), iron (CSF-iron) and ferritin (CSF-ferritin) in the CSF were highly elevated at diagnosis. After surgery, the levels of CSF-t-tau and CSF-p-tau were markedly reduced while CSF-iron and CSF-ferritin had not decreased. It is suggested that CSF-t-tau and CSF-p-tau reflected the neural damage in SS and were useful to evaluate the effectiveness of SS therapies. © 2009 Elsevier B.V. All rights reserved.

This article describes a case of cervicothoracic giant cell tumor expanding into the superior mediastinum treated by total spondylectomy. A 42-year-old-man presented with back pain and paraparesis. Magnetic resonance imaging revealed the collapse of the T2 vertebral body. The spinal cord was severely compressed by the tumor mass. The tumor had spread from T2 to the mediastinum, so that the tumor was in contact with many vital structures. To resect the tumor completely, total spondylectomy from T1 to T3 was performed through a combined anterior-posterior approach. The tumor was dissected from the vital structures using an anterior low cervical approach and splitting one-third of the sternum. En bloc vertebral resection from Th1 to Th3, including the tumor pseudocapsule, was possible through a posterior approach. The tumor around the nerve roots or dura was resected piece by piece since it was possible to separate the capsulated tumor from the dura. Splitting one-third of the sternum allowed separation of the tumor from the anterior vital structures, under direct vision. This allowed en bloc vertebral resection of the tumor that had spread to the mediastinum from T2 and in the craniocaudal direction from T1 to T3. Although giant cell tumor is benign, it can be locally aggressive. Complete excision of a giant cell tumor is the best treatment option even for the cervicothoracic spine, to protect the vital structures or neural function.