Characteristics of Postoperative C5 Palsy Following Anterior Decompression and Fusion Surgery for Cervical Degenerative Disorders: Trends Associated with Advancements in Surgical Technique.

OBJECTIVE: To investigate trends in the characteristics of postoperative C5 palsy following anterior decompression and fusion associated with advancements in this surgical procedure to treat cervical degenerative disorders. METHODS: We included 801 consecutive patients who underwent anterior decompression and fusion for cervical degenerative disorders from 2006 to 2019 and investigated the incidence, onset, and prognosis of C5 palsy. In addition, we compared the incidence of C5 palsy with that found in our previous investigation. RESULTS: The cases of 42 (5.2%) patients were complicated by C5 palsy. For patients with ossification of the longitudinal ligament (OPLL), 22 (12.4%) of 177 were complicated with C5 palsy, and the incidence was significantly higher than that in patients without OPLL (20 [3.2%] of 624, P < 0.01). The incidence of C5 palsy in patients without OPLL was significantly lower than that found in our previous investigation (P < 0.01). The incidence of C5 palsy in patients that required contiguous multilevel corpectomy was significantly higher in patients that required within a single corpectomy (P < 0.01). At 1-year follow-up, muscle strength in 3 (6.1%) of 49 limbs had not improved sufficiently. CONCLUSIONS: With advancements in surgical techniques which allowed necessary and sufficient spinal cord decompression and avoided unnecessary corpectomy, the incidence of C5 palsy in patients without OPLL was decreased significantly. By contrast, for patients with OPLL, the incidence of C5 palsy was similar to the incidence found previously, perhaps because a broad and contiguous multilevel corpectomy was usually needed to decompress the spinal cord sufficiently.

Comparison of clinical outcomes between laminoplasty, posterior decompression with instrumented fusion, and anterior decompression with fusion for K-line (-) cervical ossification of the posterior longitudinal ligament.

PURPOSE: The K-line, which is a virtual line that connects the midpoints of the anteroposterior diameter of the spinal canal at C2 and C7 in a plain lateral radiogram, is a useful preoperative predictive indicator for sufficient decompression by laminoplasty (LMP) for ossification of the posterior longitudinal ligament (OPLL). K-line is defined as (+) when the peak of OPLL does not exceed the K-line, and is defined as (-) when the peak of OPLL exceeds the K-line. For patients with K-line (-) OPLL, LMP often results in poor outcome. The aim of the present study was to compare the clinical outcome of LMP, posterior decompression with instrumented fusion (PDF) and anterior decompression and fusion (ADF) for patients with K-line (-) OPLL. METHODS: The present study included patients who underwent surgical treatment including LMP, PDF and ADF for K-line (-) cervical OPLL. We retrospectively compared the clinical outcome of those patients in terms of Japanese Orthopedic Association score (JOA score) recovery rate. RESULTS: JOA score recovery rate was significantly higher in the ADF group compared with that in the LMP group and the PDF group. The JOA score recovery rate in the PDF group was significantly higher than that in the LMP group. CONCLUSIONS: LMP should not be used for K-line (-) cervical OPLL. ADF is one of the suitable surgical treatments for K-line (-) OPLL. Both ADF and PDF are applicable for K-line (-) OPLL according to indications set by each institute and surgical decisions.

Multicenter prospective nonrandomized controlled clinical trial to prove neurotherapeutic effects of granulocyte colony-stimulating factor for acute spinal cord injury: analyses of follow-up cases after at least 1 year.

STUDY DESIGN: An open-labeled multicenter prospective nonrandomized controlled clinical trial. OBJECTIVE: To confirm the feasibility of using granulocyte colony-stimulating factor (G-CSF) for treatment of acute spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: We previously reported that G-CSF promotes functional recovery after compression-induced SCI in mice. On the basis of these findings, we conducted a multicenter prospective controlled clinical trial to assess the feasibility of G-CSF therapy for patients with acute SCI. METHODS: The trial ran from August 2009 to March 2011, and included 41 patients with SCI treated within 48 hours of onset. Informed consent was obtained from all patients. After providing consent, patients were divided into 2 groups. In the G-CSF group (17 patients), G-CSF (10 µg/kg/d) was intravenously administered for 5 consecutive days, and in the control group (24 patients), patients were similarly treated except for the G-CSF administration. We evaluated motor and sensory functions using the American Spinal Cord Injury Association score and American Spinal Cord Injury Association impairment scale at 1 week, 3 months, 6 months, and 1 year after onset. RESULTS: Only 2 patients did not experience American Spinal Cord Injury Association impairment scale improvement in the G-CSF group. In contrast, 15 patients in the control group did not experience American Spinal Cord Injury Association impairment scale improvement. In the analysis of increased American Spinal Cord Injury Association motor score, a significant increase in G-CSF group was detected from 1 week after the administration compared with the control group. After that, some spontaneous increase of motor score was detected in control group, but the significant increase in G-CSF group was maintained until 1 year of follow-up. CONCLUSION: Despite the limitation that patient selection was not randomized, the present results suggest the possibility that G-CSF administration has beneficial effects on neurological recovery in patients with acute SCI. LEVEL OF EVIDENCE: 3.

Two-staged hindfoot reconstruction with vascularized fibula graft for calcaneal osteomyelitis caused by methicillin-resistant Staphylococcus aureus: a case report.

Hindfoot reconstruction after calcaneal osteomyelitis is a challenging procedure designed to restore the weight bearing function of the heel and to allow a functional reconstruction of the Achilles tendon. Some patients require subtalar arthrodesis after primary calcaneal osteosyntesis or hindfoot reconstruction due to the considerable pain associated with weight-bearing caused by the irregular surface of the subtalar joint. To date, no reports have shown a case of hindfoot reconstruction with subtalar arthrodesis using a pedicled vascularized fibula graft. We report a case of a 24-year-old woman who presented with calcaneal methicillin-resistant Staphylococcus aureus osteomyelitis after open comminuted fracture due to a fall. Radical debridement of bone and soft tissue was repeated six times in combination with negative pressure wound therapy, followed by hindfoot reconstruction with pedicled vascularized fibula and subtalar arthrodesis. Good functional restoration had been achieved by the final follow-up 18 months after surgery.

Granulocyte colony-stimulating factor (G-CSF) protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI). The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats. METHODS: Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne). Recombinant human G-CSF (15.0 µg/kg) was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points. RESULTS: Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF- alpha) in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs. CONCLUSIONS: G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.

Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of thoracic myelopathy: a multicenter prospective controlled trial.

STUDY DESIGN: An open-labeled multicenter prospective controlled clinical trial. OBJECTIVE: To confirm the feasibility of granulocyte colony-stimulating factor (G-CSF) administration for patients with thoracic myelopathy. SUMMARY OF BACKGROUND DATA: Although G-CSF is best known as an important cytokine commonly used to treat neutropenia, it also has nonhematopoietic functions. Previous experimental studies have shown that G-CSF can enhance tissue regeneration of several organs, such as the heart and the brain. We previously reported that G-CSF promotes functional recovery after spinal cord injury in rodents. On the basis of those findings, we started a clinical trial of neuroprotective therapy, using G-CSF for patients with worsening symptoms of thoracic myelopathy. METHODS: Patients whose Japanese Orthopaedic Association (JOA) score for thoracic myelopathy had decreased 2 points or more during a recent 1-month period were eligible for entry. After giving informed consent, patients were assigned to G-CSF and control groups. The G-CSF group (n = 10) received G-CSF 10 µg/kg per day intravenously for 5 consecutive days. The control group (n = 14) received similar treatments as the G-CSF group except for G-CSF administration. The primary outcome was JOA recovery rate at 1 month after G-CSF administration or initial treatment. RESULTS: There was greater improvement in neurological functioning between baseline and 1-month follow-up in the G-CSF group (JOA recovery rate: 29.1 ± 20.5%) than in the control group (JOA recovery rate: 1.1 ± 4.2%) (P < 0.01). No serious adverse events occurred during or after the G-CSF administration. CONCLUSION: The results provide evidence that G-CSF administration caused neurological recovery in patients with worsening symptoms of thoracic compression myelopathy.

Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial.

OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions and could potentially be used to treat neuronal injury. To confirm the safety and feasibility of G-CSF administration for acute spinal cord injury (SCI), we have initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF. METHODS: The trial included a total of 16 SCI patients within 48 h of onset. In the first step, G-CSF (5 µg/kg/day) was intravenously administered for 5 consecutive days to 5 patients. In the second step, G-CSF (10 µg/kg/day) was similarly administered to 11 patients. We evaluated motor and sensory functions of patients using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) grade. RESULTS: In all 16 patients, neurological improvement was obtained after G-CSF administration. AIS grade increased by one step in 9 of 16 patients. A significant increase in ASIA motor scores was detected 1 day after injection (P < 0.01), and both light touch and pin prick scores improved 2 days after injection (P < 0.05) in the 10 µg group. No severe adverse effects were observed after G-CSF injection. CONCLUSION: These results indicate that intravenous administration of G-CSF (10 µg/kg/day) for 5 days is essentially safe, and suggest that some neurological recovery may occur in most patients. We suggest that G-CSF administration could be therapeutic for patients with acute SCI.

Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, Part 1: a phase I and IIa clinical trial.

OBJECTIVE: Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy. METHODS: We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 µg/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy. RESULTS: G-CSF administration suppressed the progression of myelopathy in all 15 patients. Neurological improvements in motor and sensory functions were obtained in all patients after the administration, although the degree of improvement differed among the patients. Nine patients in the 10-µg group (n=10) underwent surgical treatment at 1 month or later after G-CSF administration. In the 10-µg group, the mean JOA recovery rates 1 and 6 months after administration were 49.9±15.1 and 59.1±16.3%, respectively. On the day following the start of G-CSF therapy, the white blood cell count increased to more than 22,700 cells/mm3. It varied from 12,000 to 50,000 and returned to preadministration levels 3 days after completing G-CSF treatment. No serious adverse events occurred during or after treatment. CONCLUSION: The results indicate that G-CSF administration at 10 µg/kg/day is safe for patients with worsening symptoms of compression myelopathy and may be effective for their neurological improvement.

Image fusion for preoperative evaluation of vertebral artery in a patient with atlantoaxial vertical subluxation and chronic renal failure.

For preoperative evaluation of the vertebral artery (VA) at the craniovertebral junction, 3-dimensional (3-D) computed tomography (CT) angiography can simultaneously and precisely depict the location of the VA and the circumferential osseous tissues. However, this procedure has the risk of contrast-induced nephropathy, especially when patients have pre-existing renal impairment. We report the case of a 73-year-old woman with rheumatoid arthritis and concomitant chronic renal failure in whom severe myelopathy developed due to atlantoaxial vertical subluxation and subaxial subluxation. We planned to perform C1 laminectomy and C3-C7 laminoplasty, but to avoid the risk of intraoperative VA injury, we applied a fusion image technique of 3-D magnetic resonance (MR) angiography and co-registered 3-D CT that allowed for virtual assessment preoperatively of the VA courses, instead of 3-D CT angiography. Through the 3-D hybrid MR angiography-CT images, we could predict, in detail, the VA courses and the surrounding bony structures. At surgery, we found that the locations of the VAs were identical to that predicted on the preoperative image fusion analysis. We conclude that our image fusion techniques possess accurate diagnostic value for detecting arterial course, and could be applicable for patients in whom administration of contrast media should be avoided due to specific conditions, such as drug allergy and chronic renal failure.

Ultrasound and nerve stimulation-guided L5 nerve root block.

STUDY DESIGN: Case series. OBJECTIVE: Evaluation of ultrasound and nerve stimulation-guided L5 nerve root block technique. SUMMARY OF BACKGROUND DATA: Ultrasound-guided peripheral nerve block has become clinically applied. However, selective lumbosacral nerve root block is conducted under radiographic guidance, which involves patients and operators being exposed to radiation. In addition, it cannot be carried out easily during outpatient visits or at the bedside. We conducted L5 nerve root block, which is one of the most common lumbosacral nerve root block under ultrasonic guidance, using electrical nerve stimulation. METHODS: We assessed the effectiveness of ultrasound and nerve stimulation-guided L5 nerve root block on 78 patients with L5 radicular syndrome. To compare ultrasonic guidance using electrical nerve stimulation with radiographic guidance, we used a contrast agent and assessed its distribution. RESULTS: After nerve block, decreased sensation at L5 neural region and diminished/fully resolved pain was observed in all patients except for 3 in whom nerve block could not be conducted as their articular process protruded laterally. Concerning the response to stimulation, all except for these 3 felt the tapping sensation at their L5 neural regions, but no contraction of muscles was observed. The number of patients who showed an extraneural, paraneural, and intraneural pattern on contrast radiography was 71, 4, and 0, respectively. CONCLUSION: Ultrasound-guided L5 nerve root block using electrical nerve stimulation is a safe and effective method.

Surgical simulation of circumferential osteotomy and correction of cervico-thoracic kyphoscoliosis for an irreducible old C6-C7 fracture dislocation.

BACKGROUND: Many different surgical procedures have been employed in the treatment of fracture dislocation at the middle to lower cervical spine. However, consistent protocols and procedures have not been fully established for the surgical correction of an irreducible old cervical fracture dislocation associated with spinal deformity. METHODS: We report a case of irreducible cervical fracture dislocation and kyphoscoliosis, in which surgical simulation using a three-dimensional full-scale model was useful for circumferential corrective osteotomy at the C6-C7 level. A 56-year-old man was diagnosed with an irreducible fracture dislocation at the C6-C7 level 2 months after a motor vehicle accident. He showed torticollis, and complained of severe pain in his neck and left upper arm. Radiographic examinations revealed that the C6 vertebra was translated anteriorly and laterally to the C7 vertebra. A bony union had progressed at the fracture site, showing rigid cervico-thoracic kyphoscoliosis. To assist in the preoperative planning, we created a three-dimensional, full-scale model from the patient's computed tomography data. Using the model, we performed a simulation of the planned circumferential corrective osteotomy at the C6-C7 level. RESULTS: Through the simulation, we could evaluate the deformed bony structures around the vertebral arteries at the C6-C7 level accurately. At the time of the actual surgery, corrective osteotomy combined with spinal fusion (C5-T2) with a pedicle screw-rod system was accomplished successfully without any neurovascular complications. After surgery, the patient experienced relief from pain, and his neck posture became normal. CONCLUSIONS: Surgical simulation using a three-dimensional, full-scale model was useful for improving the accuracy and safety of circumferential corrective osteotomy of the cervical spine.

C1 dome-like laminotomy and posterior C1-C2 polyaxial screw-rod fixation for a patient with cervical myelopathy due to a retro-odontoid pseudotumor.

A 49-year-old man presented with progressive cervical myelopathy caused by a retro-odontoid mass, with associated developmental canal stenosis at C1, and C1-C2 instability. Surgery was scheduled for a dome-like laminotomy at C1, posterior C1-C2 fixation using C1 lateral mass screws and C2 pedicle screws, and structural bone grafting between C1 and C2. Prior to surgery, we produced a 3-dimensional full-scale model of the patient's cervical spine and performed a simulation of the scheduled surgery. Through the simulation, we accurately evaluated the laminotomy sites and the screw insertion points. During the actual surgery, all procedures were successful. After surgery, the patient's neurological deficits markedly improved. Successful C1-C2 fusion, adequate decompression of the spinal cord, and spontaneous regression of the retro-odontoid mass were achieved by this procedure without any apparent restriction in neck movement.

Reduction of cystic cavity, promotion of axonal regeneration and sparing, and functional recovery with transplanted bone marrow stromal cell-derived Schwann cells after contusion injury to the adult rat spinal cord.

OBJECT: The authors previously reported that Schwann cells (SCs) could be derived from bone marrow stromal cells (BMSCs) in vitro and that they promoted axonal regeneration of completely transected rat spinal cords in vivo. The aim of the present study is to evaluate the efficacy of transplanted BMSC-derived SCs (BMSC-SCs) in a rat model of spinal cord contusion, which is relevant to clinical spinal cord injury. METHODS: Bone marrow stromal cells were cultured as plastic-adherent cells from the bone marrow of GFPtransgenic rats. The BMSC-SCs were derived from BMSCs in vitro with sequential treatment using beta-mercaptoethanol, all-trans-retinoic acid, forskolin, basic fibroblast growth factor, platelet derived-growth factor, and heregulin. Schwann cells were cultured from the sciatic nerve of neonatal, GFP-transgenic rats. Immunocytochemical analysis and the reverse transcriptase-polymerase chain reaction were performed to characterize the BMSC-SCs. For transplantation, contusions with the New York University impactor were delivered at T-9 in 10- to 11-week-old male Wistar rats. Four groups of rats received injections at the injury site 7 days postinjury: the first received BMSCSCs and matrigel, a second received peripheral SCs and matrigel, a third group received BMSCs and matrigel, and a fourth group received matrigel alone. Histological and immunohistochemical studies, electron microscopy, and functional assessments were performed to evaluate the therapeutic effects of BMSC-SC transplantation. RESULTS: Immunohistochemical analysis and reverse transcriptase-polymerase chain reaction revealed that BMSC-SCs have characteristics similar to SCs not only in their morphological characteristics but also in their immunocytochemical phenotype and genotype. Histological examination revealed that the area of the cystic cavity was significantly reduced in the BMSC-SC and SC groups compared with the control rats. Immunohistochemical analysis showed that transplanted BMSCs, BMSC-SCs, and SCs all maintained their original phenotypes. The BMSC-SC and SC groups had a larger number of tyrosine hydroxilase-positive fibers than the control group, and the BMSC-SC group had more serotonin-positive fibers than the BMSC or control group. The BMSC-SC group showed significantly better hindlimb functional recovery than in the BMSC and control group. Electron microscopy revealed that transplanted BMSC-SCs existed in association with the host axons. CONCLUSIONS: Based on their findings, the authors concluded that BMSC-SC transplantation reduces the size of the cystic cavity, promotes axonal regeneration and sparing, results in hindlimb functional recovery, and can be a useful tool for spinal cord injury as a substitute for SCs.

Brain-derived neurotrophic factor suppresses anoikis-induced death of Schwann cells.

Anoikis is a type of apoptosis due to the detachment from the extracellular matrix and neighboring cells. In case of cell transplantation therapy for spinal cord injury, preparation of graft cells includes dissociation of cultured cells, which may cause anoikis-induced cell death. Thus suppression of anoikis may increase survival of grafted cells. Here we tested the effect of brain-derived neurotrophic factor (BDNF) on anoikis-induced cell death of cultured Schwann cells. Schwann cells were collected and cultured from sciatic nerves of neonatal Wistar rats. Schwann cells were plated upon a non-adherent polyhydroxyethyl methacrylate substrate to induce anoikis. BDNF was added into the culture medium at various concentrations. Twenty-four hours after non-adherent culture, approximately 40% of Schwann cells died and BDNF significantly decreased the number of dead cells in that culture condition. Next, Schwann cells were transplanted with or without BDNF treatment into contused rat spinal cord 1 week after injury. Five weeks after transplantation, immunohistochemistry revealed that the number of transplanted cells was significantly larger in the BDNF-treated group than that of the non-treated group. Suppression of anoikis may increase survival of grafted cells in case of cell therapy for spinal cord injury.

Granulocyte colony-stimulating factor attenuates neuronal death and promotes functional recovery after spinal cord injury in mice.

Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of granulocytic lineage cells. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for spinal cord injury (SCI) in mice. We found that G-CSF is neuroprotective against glutamate-induced cell death of cerebellar granule neurons in vitro. Moreover, we used a mouse model of compressive SCI to examine the neuroprotective potential of G-CSF in vivo. Histologic assessment with cresyl violet staining revealed that the number of surviving neurons in the injured spinal cord was significantly increased in G-CSF-treated mice. Immunohistochemistry for neuronal apoptosis revealed that G-CSF suppressed neuronal apoptosis after SCI. Moreover, administration of G-CSF promoted hindlimb functional recovery. Examination of signaling pathways downstream of the G-CSF receptor suggests that G-CSF might promote functional recovery by inhibiting neuronal apoptosis after SCI. G-CSF is currently used in the clinic for hematopoietic stimulation, and its ongoing clinical trial for brain infarction makes it an appealing molecule that could be rapidly placed into trials for patients with acute SCI.