Determining the short-term neurological prognosis for acute cervical spinal cord injury using machine learning.

It is challenging to predict neurological outcomes of acute spinal cord injury (SCI) considering issues such as spinal shock and injury heterogeneity. Deep learning-based radiomics (DLR) were developed to quantify the radiographic characteristics automatically using a convolutional neural network (CNN), and to potentially allow the prognostic stratification of patients. We aimed to determine the functional prognosis of patients with cervical SCI using machine learning approach based on MRI and to assess the ability to predict the neurological outcomes. We retrospectively analyzed the medical records of SCI patients (n=215) who had undergone MRI and had an American Spinal cord Injury Association Impairment Scale (AIS) assessment at 1 month after injury, enrolled with a total of 294 MR images. Sagittal T2-weighted MR images were used for the CNN training and validation. The deep learning framework TensorFlow was used to construct the CNN architecture. After we calculated the probability of the AIS grade using the DLR, we built the identification model based upon the random forest using 3 features: the probability of each AIS grade obtained by the DLR method, age, and the initial AIS grade at admission. We performed a statistical evaluation between the actual and predicted AIS. The accuracy, precision, recall and f1 score of the ensemble model based on the DLR and RF were 0.714, 0.590, 0.565 and 0.567, respectively. The present study demonstrates that prediction of the short-term neurological outcomes for acute cervical spinal cord injury based on MRI using machine learning is feasible.

Reduced Field-of-View Diffusion Tensor Imaging of the Spinal Cord Shows Motor Dysfunction of the Lower Extremities in Patients With Cervical Compression Myelopathy.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: The aim of this study was to quantify spinal cord dysfunction at the tract level in patients with cervical compressive myelopathy (CCM) using reduced field-of-view (rFOV) diffusion tensor imaging (DTI). SUMMARY OF BACKGROUND DATA: Although magnetic resonance imaging (MRI) is the standard used for radiological evaluation of CCM, information acquired by MRI does not necessarily reflect the severity of spinal cord disorder. There is a growing interest in developing imaging methods to quantify spinal cord dysfunction. To acquire high-resolution DTI, a new scheme using rFOV has been proposed. METHODS: We enrolled 10 healthy volunteers and 20 patients with CCM in this study. The participants were studied using a 3.0-T MRI system. For DTI acquisitions, diffusion-weighted spin-echo rFOV single-shot echo-planar imaging was used. Regions-of-interest (ROI) for the lateral column (LC) and posterior column (PC) tracts were determined on the basis of a map of fractional anisotropy (FA) of the spinal cord and FA values were measured. The FA of patients with CCM was compared with that of healthy controls and correlated with Japanese Orthopaedic Association (JOA) score. RESULTS: In LC and PC tracts, FA values in patients with CCM were significantly lower than in healthy volunteers. Total JOA scores correlated moderately with FA in LC and PC tracts. JOA subscores for motor dysfunction of the lower extremities correlated strongly with FA in LC and PC tracts. CONCLUSION: It is feasible to evaluate the cervical spinal cord at the tract level using rFOV DTI. Although FA values at the maximum compression level were not well correlated with total JOA scores, they were strongly correlated with JOA subscores for motor dysfunction of the lower extremities. Our findings suggest that FA reflects white matter dysfunction below the maximum compression level and FA can be used as an imaging biomarker of spinal cord dysfunction. LEVEL OF EVIDENCE: 4.

Diffusion tensor imaging can predict surgical outcomes of patients with cervical compression myelopathy.

PURPOSE: The aim of this study was to assess the potential role of diffusion tensor imaging (DTI) as a predictor of surgical outcomes in patients with cervical compressive myelopathy (CCM). Surgical decompression is often recommended for symptomatic CCM. It is important to know the prognosis of surgical outcomes and to recommend appropriate timing for surgery. METHODS: We enrolled 26 patients with CCM who underwent surgery. The Japanese Orthopaedic Association (JOA) score for cervical myelopathy was evaluated before and 6 months after surgery. Surgical outcomes were regarded as good if there was a change in JOA score of three points or more, or the recovery rate of JOA score was 50% or more. The patients were examined using a 3.0 T magnetic resonance system before surgery. Measured diffusion parameters were fractional anisotropy (FA) and mean diffusivity (MD). The correlations between DTI parameters and surgical outcomes were analyzed. RESULTS: Both change and recovery rate of JOA score moderately correlated with FA. Furthermore, the area under the receiver-operator characteristic curve based on FA for prognostic precision of surgical outcomes indicates that FA is a good predictive factor. The cut-off values of FA for predicting good surgical outcomes evaluated by change and recovery rate of JOA score were 0.65 and 0.57, respectively. Neither change nor recovery rate of JOA score correlated with MD. CONCLUSIONS: FA in spinal cord DTI can moderately predict surgical outcomes. DTI can serve as a supplementary tool for decision-making to guide surgical intervention in patients with CCM.

Exploration of Spinal Cord Aging-Related Proteins Using a Proteomics Approach.

How aging affects the spinal cord at a molecular level is unclear. The aim of this study was to explore spinal cord aging-related proteins that may be involved in pathological mechanisms of age-related changes in the spinal cord. Spinal cords of 2-year-old and 8-week-old female Sprague-Dawley rats were dissected from the animals. Protein samples were subjected to 2-dimentional polyacrylamide gel electrophoresis followed by mass spectrometry. Screened proteins were further investigated with immunohistochemistry and Western blotting. Among the screened proteins, we selected α-crystallin B-subunit (αB-crystallin) and peripherin for further investigation because these proteins were previously reported to be related to central nervous system pathologies. Immunohistochemistry and Western blotting revealed significant upregulation of αB-crystallin and peripherin expression in aged rat spinal cord. Further exploration is needed to elucidate the precise mechanism and potential role of these upregulated proteins in spinal cord aging processes.

Tract-Specific Diffusion Tensor Imaging Reveals Laterality of Neurological Symptoms in Patients with Cervical Compression Myelopathy.

BACKGROUND: Patients with cervical compression myelopathy (CCM) generally present bilateral neurological symptoms in their extremities. However, a substantial portion of patients with CCM exhibit laterality of neurological symptoms. The aim of this study was to assess the correlation between intrinsic structural damage and laterality of symptoms using spinal cord diffusion tensor imaging (DTI) of the corticospinal tract. METHODS: We enrolled 10 healthy volunteers and 40 patients with CCM in this study. We evaluated motor function using the American Spinal Injury Association (ASIA) motor score for left and right extremities. For DTI acquisitions, a 3.0-T magnetic resonance imaging system with diffusion-weighted spin-echo sequence was used. Regions-of-interest in the lateral column tracts were determined. We determined the correlations between fractional anisotropy (FA) and ASIA motor scores. An FA asymmetry index was calculated using left and right regions-of-interest. RESULTS: Four patients exhibited laterality of symptoms in their extremities, for which left and right ASIA scores correlated moderately with FA in the left and right lateral columns, respectively (left: ρ = 0.64, P < 0.001; right: ρ = 0.67, P < 0.001). The area under the receiver-operator characteristic curve showed that the FA asymmetry index indicated laterality of symptoms. CONCLUSIONS: Using tract-specific DTI, we demonstrated that microstructural damages in the left and right corticospinal tracts correlated with corresponding neurological symptoms in the ipsilateral side and the FA asymmetry index could indicate laterality in neurological symptoms of patients with CCM.

Outcome of posterior decompression with instrumented fusion surgery for K-line (-) cervical ossification of the longitudinal ligament.

We investigated the outcome of posterior decompression and instrumented fusion (PDF) surgery for patients with K-line (-) ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, who may have a poor surgical prognosis. We retrospectively analyzed the outcome of a series of 27 patients who underwent PDF without correction of cervical alignment for K-line (-) OPLL and were followed-up for at least 1 year after surgery. We had performed double-door laminoplasty followed by posterior instrumented fusion without excessive correction of cervical spine alignment. The preoperative Japanese Orthopedic Association (JOA) score for cervical myelopathy was 8.0 points and postoperative JOA score was 11.9 points on average. The mean JOA score recovery rate was 43.6%. The average C2-C7 angle was 2.2° preoperatively and 3.1° postoperatively. The average maximum occupation ratio of OPLL was 56.7%. In conclusion, PDF without correcting cervical alignment for patients with K-line (-) OPLL showed moderate neurological recovery, which was acceptable considering K-line (-) predicts poor surgical outcomes. Thus, PDF is a surgical option for such patients with OPLL.

Postoperative Increase in Occiput-C2 Angle Negatively Impacts Subaxial Lordosis after Occipito-Upper Cervical Posterior Fusion Surgery.

STUDY DESIGN: Retrospective case series. PURPOSE: To elucidate the impact of postoperative occiput-C2 (O-C2) angle change on subaxial cervical alignment. OVERVIEW OF LITERATURE: In the case of occipito-upper cervical fixation surgery, it is recommended that the O-C2 angle should be set larger than the preoperative value postoperatively. METHODS: The present study included 17 patients who underwent occipito-upper cervical spine (above C4) posterior fixation surgery for atlantoaxial subluxation of various etiologies. Plain lateral cervical radiographs in a neutral position at standing were obtained and the O-C2 angle and subaxial lordosis angle (the angle between the endplates of the lowest instrumented vertebra (LIV) and C7 vertebrae) were measured preoperatively and postoperatively soon after surgery and ambulation and at the final follow-up visit. RESULTS: There was a significant negative correlation between the average postoperative alteration of O-C2 angle (DO-C2) and the average postoperative alteration of subaxial lordosis angle (Dsubaxial lordosis angle) (r=-0.47, p=0.03). CONCLUSIONS: There was a negative correlation between DO-C2 and Dsubaxial lordosis angles. This suggests that decrease of mid-to lower-cervical lordosis acts as a compensatory mechanism for lordotic correction between the occiput and C2. In occipito-cervical fusion surgery, care must be taken to avoid excessive O-C2 angle correction because it might induce mid-to-lower cervical compensatory decrease of lordosis.

Addition of instrumented fusion after posterior decompression surgery suppresses thickening of ossification of the posterior longitudinal ligament of the cervical spine.

Laminoplasty (LMP) is a widely accepted surgical procedure for ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. Progression of OPLL can occur in the long term after LMP. The aim of the present study was to determine whether addition of the instrumented fusion, (posterior decompression with instrumented fusion [PDF]), can suppress progression of OPLL or not. The present study included 50 patients who underwent LMP (n=23) or PDF (n=27) for OPLL of the cervical spine. We performed open door laminoplasty. PDF surgery was performed by double-door laminoplasty followed by instrumented fusion. We observed the non-ossified segment of the OPLL and measured the thickness of the OPLL at the thickest segment with pre- and postoperative sagittal CT multi-planar reconstruction images. Postoperative CT scan revealed fusion of the non-ossified segment of the OPLL was obtained in 4/23 patients (17%) in the LPM group and in 23/27 patients (85%) in the PDF group, showing a significant difference between both groups (p=0.003). Progression of the thickness of the OPLL in the PDF group (-0.1±0.4mm) was significantly smaller than in the LMP group (0.6±0.7mm, p=0.0002). The proportion of patients showing the decrease in thickness of OPLL was significantly larger in the PDF group (6/27 patients; 22%) than in the LMP group (0/23 patients; 0%, p=0.05). In conclusion, PDF surgery can suppress the thickening of OPLL.

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.

Medially-shifted rather than high-riding vertebral arteries preclude safe pedicle screw insertion.

We enrolled 100 patients who underwent preoperative CT angiography before cervical spine instrumentation and investigated the morphology of the C2 pedicle from the perspective of pedicle screw (PS) trajectory using volume rendering and multiplanar reconstruction. The narrowest portion of the pedicle was identified as the pedicle isthmus. Safe C2 PS insertion was regarded to be not feasible when the height of the medullary cavity of the pedicle isthmus and/or width of the medullary cavity of the pedicle isthmus was ⩽4mm. Forty-five (22.5%) pedicles were ⩽4mm in width, and safe insertion of a PS was determined to be not feasible. Among these, seven pedicles were ⩽4mm in both height and width. The remaining 38 pedicles were ⩽4mm in width with heights >4mm. There was no pedicle with a width >4mm and height <4mm. In other words, short pedicles were always concomitantly narrow. Therefore, the seven pedicles ⩽4mm in both height and width were considered to be morphologically narrow. The heights of the pedicle isthmus were not limited by the vertebral artery groove (VAG) and safe C2 PS insertion can be considered feasible where the VAG is marginally cranial, whereas the widths of the pedicle isthmus are limited by the VAG. Therefore, safe C2 PS insertion is precluded only when the VAG courses cranially and medially. It is a medially-shifted, rather than a high-riding, vertebral artery that precludes safe C2 PS insertion. Therefore to avoid vertebral artery injury an axial CT scan, parallel to the pedicle axis, should be evaluated before C2 PS insertion.

Mid- to long-term outcomes of posterior decompression with instrumented fusion for thoracic ossification of the posterior longitudinal ligament.

Posterior decompression with instrumented fusion (PDF) surgery has been previously reported as a relatively safe surgical procedure for any type of thoracic ossification of the longitudinal ligament (OPLL). However, mid- to long-term outcomes are still unclear. The aim of the present study was to elucidate the mid- to long-term clinical outcome of PDF surgery for thoracic OPLL patients. The present study included 20 patients who had undergone PDF for thoracic OPLL and were followed for at least 5years. Increment change and recovery rate of the Japanese Orthopaedic Association (JOA) score were assessed. Revision surgery during the follow-up period was also recorded. Average JOA scores were 3.5 preoperatively and 7.1 at final follow-up. The average improvement in JOA score was 3.8 points and the average recovery rate was 47.0%. The JOA score showed gradual increase after surgery, and took 9months to reach peak recovery. As for neurological complications, two patients suffered postoperative paralysis, but both recovered without intervention. Six revision surgeries in four patients were related to OPLL. Additional anterior thoracic decompression for remaining ossification at the same level of PDF surgery was performed in one patient. Decompression surgery for deterioration of symptoms of pre-existing cervical OPLL was performed in three patients. One patient had undergone lumbar and cervical PDF surgery for de novo ossification foci of the lumbar and cervical spine. PDF surgery for thoracic OPLL is thus considered a relatively safe and stable surgical procedure considering the mid- to long-term outcomes.

Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice.

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration is needed to move forward to clinical application.

Resolution of low back symptoms after corrective surgery for dropped-head syndrome: a report of two cases.

BACKGROUND: Cervical deformity can influence global sagittal balance. We report two cases of severe low back pain and lower extremity radicular pain associated with dropped-head syndrome. Symptoms were relieved by cervical corrective surgery. CASE PRESENTATION: Two Japanese women with dropped head syndrome complained of severe low back pain and lower extremity radicular pain on walking. Radiographs showed marked cervical spine kyphosis and lumbar spine hyperlordosis. After cervicothoracic posterior corrective fusion was performed, cervical kyphosis was corrected and lumbar lordosis decreased, and low back pain and leg pain were relieved in both patients. CONCLUSIONS: Cervical deformity can influence global sagittal balance. Marked cervical kyphosis in patients with dropped-head syndrome can induce compensatory thoracolumbar hyperlordosis. Low back symptoms in patients with dropped-head syndrome are attributable to this compensatory lumbar hyperlordosis. Symptoms of lumbar canal stenosis may result from cervical deformity and can be improved with cervical corrective surgery.

Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats.

Spinal cord injury (SCI) can cause neuropathic pain (NeP), often reducing a patient's quality of life. We recently reported that granulocyte colony-stimulating factor (G-CSF) could attenuate NeP in several SCI patients. However, the mechanism of action underlying G-CSF-mediated attenuation of SCI-NeP remains to be elucidated. The purpose of the present study was to elucidate the therapeutic effect and mechanism of action of granulocyte colony-stimulating factor for SCI-induced NeP. T9 level contusive SCI was introduced to adult male Sprague Dawley rats. Three weeks after injury, rats received intraperitoneal recombinant human G-CSF (15.0 µg/kg) for 5 days. Mechanical allodynia was assessed using von Frey filaments. Immunohistochemistry and western blot analysis were performed in spinal cord lumbar enlargement samples. Testing with von Frey filaments showed significant increase in the paw withdrawal threshold in the G-CSF group compared with the vehicle group 4 weeks, 5 weeks, 6 weeks and 7 weeks after injury. Immunohistochemistry for CD11b (clone OX-42) revealed that the number of OX-42-positive activated microglia was significantly smaller in the G-CSF group than that in the vehicle rats. Western blot analysis indicated that phosphorylated-p38 mitogen-activated protein kinase (p38MAPK) and interleukin-1ß expression in spinal cord lumbar enlargement were attenuated in the G-CSF-treated rats compared with that in the vehicle-treated rats. The present results demonstrate a therapeutic effect of G-CSF treatment for SCI-induced NeP, possibly through the inhibition of microglial activation and the suppression of p38MAPK phosphorylation and the upregulation of interleukin-1ß.

Neurological deterioration induced by sitting in patients after cervicothoracic posterior decompression with instrumented fusion surgery for ossification of the longitudinal ligament: two cases reports.

BACKGROUND: We report on Japanese patients who showed neurological deterioration induced by sitting after cervicothoracic posterior decompression with instrumented fusion, but showed immediate neurological recovery after bed rest. CASE PRESENTATION: Patients showed incomplete paraparesis caused by the ossification of the posterior longitudinal ligament at uppermost thoracic spine. Cervicothoracic posterior decompression with instrumented fusion was performed. Postoperatively, the patients showed partial paraparesis when they were sitting. They showed rapid recovery from lower extremity paralysis upon lying down. After strict bed rest for one month, those patients showed no apparent development of paralysis during sitting. CONCLUSION: In patients with postoperative residual anterior spinal cord compression, micromotion might exacerbate neurological symptoms.

Bone union and remodelling of the non-ossified segment in thoracic ossification of the posterior longitudinal ligament after posterior decompression and fusion surgery.

PURPOSE: The motion at the non-ossified segment of the ossification of the posterior longitudinal ligament (OPLL) is thought to be highly correlated to aggravation of symptoms of myelopathy. The rationale for posterior decompression with instrumented fusion (PDF) surgery is to limit the motion of the non-ossified segment of OPLL by stabilization. The purpose of the present study was to elucidate the course of bone union and remodelling of the non-ossified segment of thoracic OPLL (T-OPLL) after PDF surgery. METHODS: A total of 29 patients who underwent PDF surgery for T-OPLL were included in this study. We measured the thickness of the OPLLs by determining the thickest part of the OPLL in the sagittal multi-planer reconstruction CT images pre- and post-operatively. Five experienced spine surgeons independently performed CT measurements of OPLL thickness twice. Japanese Orthopaedic Association score for thoracic myelopathy was measured as clinical outcome measure. RESULTS: Non-ossified segment of OPLLs fused in 24 out of 29 (82.8 %) patients. The average thickness of the OPLL at its thickest segment was 8.0 mm and decreased to 7.3 mm at final follow-up. The decrease in ossification thickness was significantly larger in the patients who showed fusion of non-ossified segments of OPLL compared with that in the patients did not show fusion. There was no significant correlation between the clinical outcome and the decrease in thickness of the OPLLs. CONCLUSION: The results of this study showed that remodelling of the OPLLs, following fusion of non-ossified segment of OPLLs, resulted in a decreased OPLL thickness, with potential for a reduction of spinal cord compression.

Elderly onset intramedullary epidermoid cyst in the conus medullaris: a case report.

INTRODUCTION: Epidermoid cysts are known as embryonic or acquired ectopic aberrations of the ectoderm. To the best of our knowledge, there are only a few reports of elderly onset intramedullary epidermoid cysts. We report a case of elderly onset intramedullary epidermoid cyst at the conus medullaris. CASE PRESENTATION: A 63-year-old Japanese woman working as a farmer presented with slowly progressive gait disturbance and voiding dysfunction. A magnetic resonance imaging scan revealed an intramedullary mass lesion at L1 to L3. We diagnosed the lesion as an intramedullary spinal cord tumor. A laminectomy was performed at the level of Th12 to L3. Upon spinal cord dissection, a yellowish milky exudation erupted from the cystic lesion. We resected white cartilage-like pieces from the cystic cavity. Because the wall of the cystic lesion tightly adhered to the spinal cord parenchyma, we abandoned complete resection of the cyst wall. The pathological diagnosis was an epidermoid cyst. CONCLUSIONS: We propose that evacuation of the cyst contents is preferable, especially in cases with elderly onset and congenital origin.

Neuroprotective therapy with granulocyte colony-stimulating factor in acute spinal cord injury: a comparison with high-dose methylprednisolone as a historical control.

PURPOSE: We performed a phase I/IIa clinical trial and confirmed the safety and feasibility of granulocyte colony-stimulating factor (G-CSF) as neuroprotective therapy in patients with acute spinal cord injury (SCI). In this study, we retrospectively analyzed the clinical outcome in SCI patients treated with G-CSF and compared these results to a historical cohort of SCI patients treated with high-dose methylprednisolone sodium succinate (MPSS). METHODS: In the G-CSF group (n = 28), patients were treated from August 2009 to July 2012 within 48 h of the injury, and G-CSF (10 µg/kg/day) was administered intravenously for five consecutive days. In the MPSS group (n = 34), patients underwent high-dose MPSS therapy from August 2003 to July 2005 following the NASCIS II protocol. We evaluated the ASIA motor score and the AIS grade elevation between the time of treatment and 3-month follow-up and adverse events. RESULTS: The ΔASIA motor score was significantly higher in the G-CSF group than in the MPSS group (p < 0.01). When we compared AIS grade elevation in patients with AIS grades B/C incomplete paralysis, 17.9% of patients in the G-CSF group had an AIS grade elevation of two steps compared to 0% of patients in the MPSS group (p < 0.05), and the incidence of pneumonia was significantly higher in the MPSS group (42.9%) compared to the G-CSF group (8.3%) (p < 0.05). CONCLUSIONS: These results suggest that G-CSF administration is safe and effective, but a prospective randomized controlled clinical trial is needed to compare the efficacy of MPSS versus G-CSF treatment in patients with SCI.

Delayed granulocyte colony-stimulating factor treatment in rats attenuates mechanical allodynia induced by chronic constriction injury of the sciatic nerve.

STUDY DESIGN: Animal experimental study with intervention. OBJECTIVE: The aim of this study was to elucidate therapeutic effects of delayed granulocyte colony-stimulating factor treatment for mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. SUMMARY OF BACKGROUND DATA: Granulocyte colony-stimulating factor (G-CSF) is used clinically for patients with hematological disorders. Previous reports showed that immediate G-CSF attenuates neuropathic pain in CCI of the sciatic nerve. However, the acute treatment for neuropathic pain prior to accurate diagnosis is not realistic in clinical settings. METHODS: Adult, female Sprague-Dawley rats were subjected to the CCI model. This model induces mechanical allodynia on the ipsilateral hind paw within the first week after the injury. One week after CCI, rats received intraperitoneal G-CSF (15.0 µg/kg) for 5 consecutive days. Mechanical allodynia was assessed using the von Frey hair test. Immunohistochemistry for phosphorylated p38 mitogen-activated kinase (p-p38MAPK) and OX-42 (a marker for activated microglia) on tissue slides from a subset of rats 2 weeks after surgery. Western blot analyses were carried out to determine protein expression level of p-p38MAPK and interleukin-1 ß on spinal cord homogenates 2 weeks after CCI. RESULTS: Results of the von Frey filament test showed that G-CSF significantly attenuates mechanical allodynia induced by the CCI model. Immunohistochemistry revealed that G-CSF reduced the number of p-p38MAPK-positive cells in the ipsilateral dorsal horn compared with that in the vehicle group rats. Immunofluorescent double staining revealed that p-p38MAPK-expressing cells in the spinal cord dorsal horn are mainly microglia. Western blot analysis indicated that G-CSF decreased the expression levels of both p-p38MAPK and interleukin-1 ß in the ipsilateral dorsal horn compared with that in the vehicle group rats. CONCLUSION: The present results indicate a beneficial effect of delayed G-CSF treatment in an animal model of peripheral nerve injury-induced neuropathic pain. LEVEL OF EVIDENCE: N/A.