Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells.

BACKGROUND: Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. METHODS: In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. RESULTS: The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. CONCLUSION: Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment. Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Brain-specific Pd1 deficiency leads to cortical neurogenesis defects and depressive-like behaviors in mice.

Embryonic neurogenesis is tightly regulated by multiple factors to ensure the precise development of the cortex. Deficiency in neurogenesis may result in behavioral abnormalities. Pd1 is a well-known inhibitory immune molecule, but its function in brain development remains unknown. Here, we find brain specific deletion of Pd1 results in abnormal cortical neurogenesis, including enhanced proliferation of neural progenitors and reduced neuronal differentiation. In addition, neurons in Pd1 knockout mice exhibit abnormal morphology, both the total length and the number of primary dendrites were reduced. Moreover, Pd1cKO mice exhibit depressive-like behaviors, including immobility, despair, and anhedonia. Mechanistically, Pd1 regulates embryonic neurogenesis by targeting Pax3 through the ß-catenin signaling pathway. The constitutive expression of Pax3 partly rescues the deficiency of neurogenesis in the Pd1 deleted embryonic brain. Besides, the administration of ß-catenin inhibitor, XAV939, not only rescues abnormal brain development but also ameliorates depressive-like behaviors in Pd1cKO mice. Simultaneously, Pd1 plays a similar role in human neural progenitor cells (hNPCs) proliferation and differentiation. Taken together, our findings reveal the critical role and regulatory mechanism of Pd1 in embryonic neurogenesis and behavioral modulation, which could contribute to understanding immune molecules in brain development.

Single-cell transcriptomics reveals ependymal subtypes related to cytoskeleton dynamics as the core driver of syringomyelia pathological development.

Syringomyelia is a common clinical lesion associated with cerebrospinal fluid flow abnormalities. By a reversible model with chronic extradural compression to mimic human canalicular syringomyelia, we explored the spatiotemporal pathological alterations during syrinx development. The most dynamic alterations were observed in ependymal cells (EPCs), oligodendrocyte lineage, and microglia, as a response to neuroinflammation. Among different cell types, EPC subtypes experienced obvious dynamic alterations, which were accompanied by ultrastructural changes involving the ependymal cytoskeleton, cilia, and dynamic injury in parenchyma primarily around the central canal, corresponding to the single-cell transcripts. After effective decompression, the syrinx resolved with the recovery of pathological damage and overall neurological function, implying that for syringomyelia in the early stage, there was still endogenous repair potential coexisting with immune microenvironment imbalance. Ependymal remodeling and cilia restoration might be important for better resolution of syringomyelia and parenchymal injury recovery.

Efficacy of Tracheal Traction Exercise for Prevention of Laryngopharyngeal Complications Following Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Tracheal traction exercise (TTE) has been proposed as a preventative measure for laryngopharyngeal complications following anterior cervical discectomy and fusion. However, the exact effects of TTE remain controversial. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy of TTE. METHODS: We systematically searched PubMed, Web of Science, Embase, Cochrane, ClinicalTrials.gov, China National Knowledge Infrastructure, WANFANG DATA, VIP citation databases, and Chinese BioMedical Literature Database for randomized controlled trials (published between January 1, 2000, and January 23, 2023, without language restrictions) comparing the TTE group to the control group (non-TTE group). We assessed the risk of bias using Cochrane risk of bias assessment tool. Our primary end points were operation duration, the number of patients with postoperative dysphagia, and Visual Analog Scale (VAS) for laryngopharyngeal pain. We used a fixed-effects model to assess the pooled data. RESULTS: Of the 823 identified studies, 5 were eligible and included in our analysis (N = 542 participants). Compared with the control group, TTE reduced the incidence of postoperative dysphagia (relative risk = 0.41, 95% confidence interval [CI]: 0.28, 0.61, P < 0.05) and operation duration (weighted mean difference = -10.24, 95% CI: -14.48, -6.00, P < 0.05). However, no significant difference was observed in postoperative VAS between the 2 groups (weighted mean difference = -0.11, 95% CI: -0.23, 0.11, P = 0.08 > 0.05). CONCLUSIONS: TTE can effectively reduce operation duration and postoperative dysphagia. However, it does not result in a significant difference in postoperative VAS.

Suppression of TGFßR-Smad3 pathway alleviates the syrinx induced by syringomyelia.

BACKGROUND: Syringomyelia is a cerebrospinal fluid (CSF) disorder resulted in separation of pain and temperature, dilation of central canal and formation of syrinx in central canal. It is unclear about mechanisms of the dilation and syrinx formation. We aimed to investigate roles of ependymal cells lining central canal on the dilation, trying to reduce syrinx formation in central canal. METHODS: We employed 78 Sprague-Dawley (SD) rats totally with syringomyelia to detect the contribution of ependymal cells to the dilation of central canal. Immunofluorescence was used to examine the activation of ependymal cells in 54 syringomyelia rat models. BrdU was used to indicate the proliferation of ependymal cells through intraperitoneal administration in 6 syringomyelia rat models. 18 rats with syringomyelia were injected with SIS3, an inhibitor of TGFßR-Smad3, and rats injected with DMSO  were used as control. Among the 18 rats, 12 rats were used for observation of syrinx following SIS3 or DMSO administration by using magnetic resonance imaging (MRI) on day 14 and day 30 under syringomyelia without decompression. All the data were expressed as mean ± standard deviation (mean ± SD). Differences between groups were compared using the two-tailed Student's t-test or ANOVA. Differences were considered significant when *p < 0.05. RESULTS: Our study showed the dilation and protrusions of central canal on day 5 and enlargement from day 14 after syringomyelia induction in rats with activation of ependymal cells lining central canal. Moreover, the ependymal cells contributed to protrusion formation possibly through migration along with central canal. Furthermore, suppression of TGFßR-Smad3 which was crucial for migration reversed the size of syrnix in central canal without treatment of decompression, suggesting TGFßR-Smad3 signal might be key for dilation of central canal and formation of syrinx. CONCLUSIONS: The size of syrinx was decreased after SIS3 administration without decompression. Our study depicted the mechanisms of syrinx formation and suggested TGFßR-Smad3 signal might be key for dilation of central canal and formation of syrinx.

Impairment of Connexin 43 may initiate cilia decline in syringomyelia.

Ependymal cilia, which are maintained by the Connexin 43 (Cx43) and protected by the actin network, play an essential role in regulating cerebrospinal fluid (CSF) circulation. The decline of ependymal cilia has been reported in syringomyelia, but the underlying mechanism remains unclear. In this study, we used an extradural compression-induced syringomyelia rat model to investigate the changes in cilia and related pathologies during the formation of syringomyelia. We divided rats into control and syringomyelia groups and sacrificed them at three time points, 7, 14, and 28 days postoperative (dpo). Scanning electron microscopy (SEM) and immunofluorescence (IF) were used to illustrate the number and morphology of ependymal cilia. IF was also used to show the status of centrioles, actin network, and Cx43 (the main component of the gap junction). Transmission electron microscopy (TEM) was used to observe the structure of the gap junction. The results showed that most syringomyelia were located at segments (T10-12) rostral to the compression site (T13). SEM images showed that the number of cilia in the central canal (CC) declined in two phases during the development of syringomyelia (early stage, 7 dpo; later stage, 14 and 28 dpo). The number of cilia showed a significant difference between the early and later stages of syringomyelia development. Additionally, TEM showed the absence of gap junction and IF illustrated less Cx43 expression in ependymal cells (ECs) at the compression site in both the early and later stages. Actin network disruption and centrioles reduction at adjacent segments rostral to the compression site were found in the later stage. These findings indicate that the loss of Cx43 at the compression site may be related to cilia detachment at rostral adjacent segments by disrupting intercellular communication in the early stage of syringomyelia development. This early cilia decline then causes actin network disorganization, further aggravating cilia decline by exposing centrioles to CSF shear stress in the later stage. These findings suggest a potential mechanism of ependymal cilia decline in the development of syringomyelia and may provide a novel perspective for future research in this area.

Correlation Among Syrinx Resolution, Cervical Sagittal Realignment, and Surgical Outcome After Posterior Reduction for Basilar Invagination, Atlantoaxial Dislocation, and Syringomyelia.

BACKGROUND: The correlation among syrinx resolution, occipitoaxial sagittal alignment, and surgical outcome in long-term follow-up seems to have not been clarified. OBJECTIVE: To further explore the relationship between the syrinx resolution and occipitoaxial realignment after posterior reduction and fixation in basilar invagination (BI)-atlantoaxial dislocation (AAD) patients with syringomyelia. METHODS: A continuous series of 32 patients with BI-AAD and syringomyelia who received direct posterior reduction met the inclusion criteria of this study. Their clinical and imaging data were analyzed retrospectively. Before surgery and at the last follow-up, we used the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI) to assess the neurological status, respectively. The Pearson correlation coefficient and multiple stepwise regression analysis were used to explore the relevant factors that may affect surgical outcomes. RESULTS: There were significant differences in atlantodental interval, clivus-axial angle, occiput-C2 angle (Oc-C2A), cervicomedullary angle (CMA), subarachnoid space (SAS) at the foramen magnum (FM), syrinx size, NDI, and JOA score after surgery compared with those before surgery. ΔCMA and the resolution rate of syrinx/cord as relevant factors were correlated with the recovery rate of JOA (R 2 = 0.578, P < .001) and NDI (R 2 = 0.369, P < .01). What's more, ΔSAS/FMD (SAS/FM diameter) and ΔOc-C2A were positively correlated with the resolution rate of syrinx/cord (R 2 = 0.643, P < .001). CONCLUSION: With medulla decompression and occipital-cervical sagittal realignment after posterior reduction and fusion for BI-AAD patients with syringomyelia, the structural remodeling of the craniovertebral junction and occipitoaxial realignment could contribute to syringomyelia resolution.

Comparison of 3D-printed Navigation Template-assisted Pedicle Screws versus Freehand Screws for Scoliosis in Children and Adolescents: A Systematic Review and Meta-analysis.

BACKGROUND: There is a lack of attention to screw placement techniques for surgical treatment of scoliosis in children and adolescents. This meta-analysis aims to compare the accuracy and safety of pedicle screw placement between the 3D-printed navigation template technique and the freehand technique during corrective surgery for scoliosis in children and adolescents. METHODS: A comprehensive search was conducted for relevant articles up to December 2021 in databases including PubMed, Embase, MEDLINE, Cochrane, and Web of Science. The systematic meta-analysis compared the efficacy of pedicle screw placement between the two techniques, including accuracy of pedicle screw placement, complication rate, operation time, blood loss, mean placement time per screw, and mean times for fluoroscopy. RESULTS: The seven articles analyzed in this study involved 229 patients altogether. A total of 2,805 pedicle screws were placed by the two methods. Our results revealed that the 3D-printed guide template technique was more accurate than the freehand technique in pedicle screw placement (odds ratio [OR] =2.96; 95% confidence interval [CI]: 2.24-3.91; p < 0.000) with a lower complication rate (OR = 0.21; 95% CI: 0.06-0.78; p = 0.02). The operation time (mean difference [MD] = -34.37; 95% CI: -67.47 to -1.28; p = 0.04) and mean placement time per screw (MD = -3.11; 95% CI: -6.13 to -0.09; p = 0.04) and mean times for fluoroscopy (MD = -6.60; 95% CI: -8.66 to -4.55; p < 0.000) significantly decreased among patients in the 3D-printed navigation template group compared with those in the freehand technique group. In addition, the two techniques had no significant statistical difference in blood loss. CONCLUSIONS: Compared with the traditional freehand technique, the 3D-printed guide template is a promising technique with higher accuracy and safety in screw placement for surgical treatment of scoliosis in children and adolescents, and is worth popularizing and validating through more prospective clinical studies.

The Physiological Occlusion of the Central Canal May Be a Prerequisite for Syringomyelia Formation.

OBJECTIVE: Syringomyelia is a common central nervous system disease characterized by the dilation of the central canal (CC). Regarding the pathogenesis of syringomyelia, cerebrospinal fluid (CSF) circulation obstruction in the subarachnoid space (SAS) of the spinal cord has been widely accepted. However, clinical and animal studies on obstructing the CSF in SAS failed to form syringomyelia, challenging the theory of SAS obstruction. The precise pathogenesis remains unknown. METHODS: We utilized an extradural compression rat model to investigate the pathogenesis underlying syringomyelia. Magnetic resonance imaging enabled detection of syringomyelia formation. To assess CSF flow within the SAS, Evans blue was infused into the cisterna magna. Histological analysis allowed morphological examination of the CC. Furthermore, CSF flow through the CC was traced using Ovalbumin Alexa-Flour 647 conjugate (OAF-647). Scanning electron microscopy (SEM) enabled visualization of ependymal cilia. RESULTS: The findings showed that the dura mater below the compression segment exhibited lighter coloration relative to the region above the compression, indicative of partial obstruction within the SAS. However, the degree of SAS occlusion did not significantly differ between syringomyelia (SM-Y group) and those without (SM-N group). Intriguingly, hematoxylin and eosin staining and CSF tracing revealed occlusion of the CC accompanied by reduced CSF flow in the SM-Y group compared to SM-N and control groups. SEM images uncovered impairment of ependymal cilia inside the syringomyelia. CONCLUSION: CC occlusion may represent a physiological prerequisite for syringomyelia formation, while SAS obstruction serves to initiate disease onset. The impairment of ependymal cilia appears to facilitate progression of syringomyelia.

Phenotypes and Prognostic Factors of Syringomyelia in Single-Center Patients With Chiari I Malformation: Moniliform Type as a Special Configuration.

OBJECTIVE: The specific association between morphometric characteristics of the syrinx and the prognosis of Chiari malformation type I (CM-I) with syringomyelia following surgical procedure seems to have not been fully elaborated. This study focused on the preoperative clinical and radiologic parameters in CM-I patients with syringomyelia to find out the relationship between the patients' clinical status and the phenotypes of the syrinx with surgical outcome. METHODS: A continuous series of pediatric and adult patients with CM-I and syringomyelia from a prospectively maintained database in a single center were included, and we explored the related factors affecting the prognosis following decompression surgery through retrospective analysis of clinical presentations, imaging characteristics, and the morphological features of syringomyelia, to provide a clinical reference for the treatment of syringomyelia. RESULTS: There were 28 pediatric patients (13.8%), and 174 adults (86.2%) included in our study. The average Chicago Chiari Outcome Scale score was 14.56 ± 1.78. The overall prognosis after surgery was good in our series, among them 152 cases (75.25%) with a favorable prognosis, and syrinx was resolved effectively in 172 cases (85.15%). According to the univariate and multivariate analyses, the preoperative symptom duration, observation time, and with/without moniliform type were independent factors affecting the prognosis in adults. The most obvious difference between moniliform type and nonmoniliform type lies in the preoperative symptom duration, ventral subarachnoid space at the foramen magnum, and with/without straightened cervical physio-curve. CONCLUSION: Timely decompression surgery could achieve a better outcome in CM-I patients with syringomyelia. Moniliform syringomyelia may suggest a relatively better prognosis.

The effect of local intraoperative corticosteroid application on postoperative dysphagia following anterior cervical spine surgery.

Dysphagia is a common complication following anterior cervical spine surgery (ACSS). Although several literatures have reported the potential benefit of local corticosteroid application on dysphagia, its safety and efficacy are still unclear. A systematic review was performed aiming to evaluate the evidence of local corticosteroid application in prevention or treatment of postoperative dysphagia following ACSS. A systematic search was performed in September 2018 in PubMed and Embase database. The following information was extracted: study investigator, year of publication, number of patients, study design, inclusion/exclusion criteria, administration protocol of steroid, type of surgical procedure, number of levels performed, assessment methodology of dysphagia, radiologic assessment of prevertebral soft tissue swelling (PSTS), follow-up time points, outcome of dysphagia, and corticosteroid-related complications. Qualitative synthesis was performed. Finally, 5 studies met the inclusion/exclusion criteria. Four studies found that local corticosteroid application could decrease the incidence and magnitude of postoperative dysphagia while 1 study showed no effect on dysphagia significantly at 6 weeks and 3 months follow-up time. A total of 2325 patients received local corticosteroid intraoperatively; no early corticosteroid-related complication was reported. Totally, 4 adverse events occurred in long-term follow-up time, including 2 bone nonunion at 1.5 and 2.5 years postoperatively, 2 esophageal perforation at 2 months and 11 months of follow-up, respectively. Local corticosteroid application can reduce the incidence and severity of dysphagia following ACSS without increasing early corticosteroid-related complications. But further high-quality study is necessary to analyze potential delayed complications.

Relationship Between Syrinx Resolution and Cervical Sagittal Realignment Following Decompression Surgery for Chiari I Malformation Related Syringomyelia Based on Configuration Phenotypes.

OBJECTIVE: Combined with different configuration types of syringomyelia, to analyze the correlation between syrinx resolution and changes in cervical sagittal alignment following Foramen magnum and Magendie dredging (FMMD) for syringomyelia associated with Chiari I malformation (CM-I), and to further explore the respective relationship with clinical outcome. METHODS: A consecutive series of 127 patients with CM-I and syringomyelia who underwent FMMD in our center met the inclusion criteria of this study. Their clinical records and radiologic data were retrospectively reviewed. The Japanese Orthopedic Association (JOA) scoring system and the Chicago Chiari Outcome Scale (CCOS) were used to evaluate the surgical efficacy. The phenotypes of syringomyelia and the clinical characteristics of the patients were analyzed according to grouping by cervical curvature at baseline. RESULTS: The preoperative straight or kyphotic cervical alignment is more common in the moniliform syrinx. After surgery, the syrinx resolution and cervical sagittal realignment in the moniliform group are more obvious, and the corresponding prognosis is relatively better. Spearman correlation analysis showed that the ΔS/C ratio (the change ratio of syrinx/cord) was positively correlated with the CCOS (p = 0.001, r = 0.897) and ΔC2-7A (the change of lower cervical angle) (p = 0.002, r = 0.560). There was also a correlation between the ΔJOA score (the change rate of the JOA score) and ΔC2-7A (p = 0.012, r = 0.467). CONCLUSION: After decompression surgery, syrinx resolution may coexist with the changes in the subaxial lordosis angle, especially for syrinx in moniliform type, and the relationship between syrinx resolution and cervical sagittal realignment might be valuable for evaluating the surgical outcome.

Clinicoradiological characteristics of primary spinal cord H3 K27M-mutant diffuse midline glioma.

OBJECTIVE: Primary spinal cord H3 K27M-mutant diffuse midline glioma (DMG) is a rare and devastating pathological entity. However, little attention has been paid to this disease. As a result, its clinicoradiological characteristics have yet to be described. The aim of this study was to describe the clinicoradiological characteristics of primary intramedullary H3 K27M-mutant DMG and to compare this tumor with the H3 K27 wild-type to explore potential features that could differentiate the two. METHODS: A total of 59 patients with pathologically confirmed intramedullary astrocytoma were included in this study. The cohort was divided into an H3 K27M-mutant group and H3 K27 wild-type group based on the status of H3 K27M according to an immunohistochemistry method. Demographic data, MRI features, and molecular information were collected. Multivariate logistic regression was conducted to investigate variables that might have a role in differentiating an H3 K27M DMG from an H3 K27 wild-type tumor. RESULTS: Only symptom duration showed an independent association with the H3 K27M mutation (OR 0.82, 95% CI 0.68-0.94, p = 0.016). Patients with spinal cord H3 K27M-mutant DMG had a shorter symptom duration than patients with H3 K27 wild-type glioma. No significant difference was found in terms of MRI features between the H3 K27M-mutant and H3 K27 wild-type groups. Additionally, H3 K27M-mutant DMG frequently demonstrated overexpression of p53. Survival outcome did not show a statistical difference between the H3 K27-mutant subgroup and H3 K27 wild-type subgroup in histologically high-grade astrocytoma. CONCLUSIONS: Symptom duration was associated with an H3 K27M mutation in intramedullary astrocytoma. MRI features were heterogeneous, and no imaging feature was able to predict the H3 K27M mutation. The H3 K27M mutation did not impact survival outcome in spinal histologically high-grade astrocytoma.

Prognostic factors and nomogram prediction of survival probability in primary spinal cord astrocytoma patients.

OBJECTIVE: Knowledge on the management of spinal cord astrocytoma (SCA) remains scarce. Here, the authors constructed and validated a predictive nomogram, often used for individualized prognosis and evaluations, to estimate cancer-specific survival (CSS) and overall survival (OS) for patients with SCA. METHODS: Epidemiological characteristics were compared between low-grade SCA (LGSCA) and high-grade SCA (HGSCA) patients from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for CSS and OS were determined using univariate and multivariate analyses and Kaplan-Meier curves. A nomogram was developed to individually predict the 3-, 5-, and 10-year CSS and OS rates. The clinical usefulness of the nomogram was assessed using calibration plots, the concordance index (C-index), and time-dependent receiver operating characteristic curves. RESULTS: A total of 468 LGSCA and 165 HGSCA patients were eligible for inclusion. LGSCA and HGSCA patients demonstrated differences in age, tumor extension, insurance status, adjuvant treatment, and survival. Multivariate analysis demonstrated that in the LGSCA group, tumor extension, surgery type, and adjuvant therapy were individually associated with CSS. The distance of tumor extension and WHO grade were individually associated with CSS in the HGSCA group. The prognostic variables were further demonstrated using the Kaplan-Meier method, which also suggested that adjuvant treatment provided no advantage to HGSCA patients. A nomogram was constructed, and the C-index for CSS was 0.84 by internal validation (95% CI 0.79-0.90). CONCLUSIONS: This research suggests that the distance of tumor extension, type of surgery, and adjuvant therapy are significant risk factors for CSS using multivariate analysis in the LGSCA group. Adjuvant treatment provided no advantages for CSS or OS in patients with HGSCAs. The nomogram may be clinically useful to healthcare providers.

A novel classification and its clinical significance in Chiari I malformation with syringomyelia based on high-resolution MRI.

BACKGROUND: The existing classification in Chiari I malformation (CM-I) has limited significance for the selection of surgical methods. OBJECTIVE: The purpose of this study was to investigate the surgery of CM-I with syringomyelia based on the high-resolution MR imaging (HRMRI) findings. METHODS: Data from 115 patients were collected and retrospectively analyzed. For those with syringomyelia up to the level of C1, HRMRI was performed and according to the communication status between the fourth ventricle and the syringomyelia, patients can be divided into four types, namely Type A: classic communicating; Type B: partial communicating; Type C: non-communicating; Type D: atrophic. All operations were performed with Foramen magnum and Magendie dredging (FMMD), and all intradural factors that may have induced the obstruction of CSF circulation were recorded. The efficiency of operation on syringomyelia was evaluated by mJOA, imaging findings, and complications in the follow-up periods. RESULTS: The postoperative follow-up period was from 12 to 24 months, with an average of 14.3 months. At 1 year, the mJOA of 115 patients was significantly higher than that before the operations (before surgery 12.1 ± 2.3 vs. after surgery 14. 2 ± 1.4, P < 0.05). In addition, postoperative re-examination showed that the size of the syringomyelia was reduced or completely resolved in patients of Type A, 100% (2/2); Type B, 81% (9/11); Type C, 84% (81/97); and Type D, 20% (1/5). CONCLUSIONS: According to our new classification based on HRMRI, FMMD is the key to surgical treatment, especially for Type A and Type B patients.

Wireless Epidural Electrical Stimulation in Combination With Serotonin Agonists Improves Intraspinal Metabolism in Spinal Cord Injury Rats.

OBJECTIVES: The combination of epidural electrical stimulation (EES) and serotonin agonists (5-HTA) effectively restores rhythmic lower-limb movements and improves intraspinal hemodynamics after spinal cord injury (SCI). Nonetheless, whether EES + 5-HTA improves intraspinal metabolism remains unclear. The present study aimed to evaluate the effects of EES + 5-HTA on intraspinal metabolism in SCI rats. MATERIALS AND METHODS: Wireless EES (WEES) implantation with complete T8 transection was performed in SCI rats. Electrodes were placed at the T12 and L2 vertebral levels. After rest for a week, the SCI rats received 11 weeks of WEES + 5-HTA treatment and treadmill training. WEES was switched off after each daily training. Locomotor function was evaluated by motion capture at week 12. Positron emission tomography-computed tomography was conducted to evaluate basal metabolism when WEES was switched off and assess task metabolism when WEES was switched on. RESULTS: With locomotor recovery after training for 11 weeks, WEES + 5-HTA conjointly improved basal metabolism (vs. each intervention alone; p < 0.05) and linearly modulated task metabolism in a frequency-dependent manner (R2 = 0.8901). Furthermore, 60 Hz of WEES was identified as the threshold for the extensive activation of the spinal cord's task metabolism below the transection plane (p < 0.05). CONCLUSIONS: WEES + 5-HTA could conjointly restore basal metabolism to a healthy level and modulate task metabolism by adjusting the stimulation frequency.

Quantitative Reduction of Basilar Invagination With Atlantoaxial Dislocation by a Posterior Approach.

OBJECTIVE: This study evaluated the feasibility and efficacy of quantitative reduction and fixation to treat basilar invagination (BI) with atlantoaxial dislocation (AAD). METHODS: Posterior occipitocervical angle (POCA), occiput-C2 angle (Oc-C2A), clivusaxial angle (CAA), and C2-7 angle (C2-7A) were considered for quantitative reduction. Twelve patients with BI complicated with AAD received posterior interarticular release and individualized cage implantation to restore vertical dislocation. The POCA was adjusted using cantilever technology to further reduce the horizontal dislocation and adjust lower cervical vertebral angle. All patients received a radiological follow-up for ≥12 months. Improvements in spinal cord function were evaluated using Japanese Orthopedic Association (JOA) score. RESULTS: All the patients received successful quantitative reduction for BI-AAD, and bony fusion was achieved without spinal cord injury after surgery for 12 months. The JOA score was improved significantly to 15.2 ± 0.9 twelve months after surgery (p < 0.01). Radiological follow-up revealed that individualized cage and POCA play vital roles in quantitative correction: (1) distance of the dens above McRae's line and atlantodens interval were restored to normal level, respectively; (2) changes in Oc-C2 angle (ΔOc-C2A), C2-7 angle (ΔC2-7A), clivus-axial angle (ΔCAA), and POCA (ΔPOCA) were all caused by changes in axis tilt. Based on the changes of radiological parameter we deduced the formula for quantitative reduction by linear regression analysis: -ΔPOCA = ΔOc-C2A = -ΔC2-7A = ΔCAA. CONCLUSION: Quantitative posterior reduction by individualized cage and adjusting ΔPOCA is feasible for treating BI with AAD.

Reconsideration of the transoral odontoidectomy in complex craniovertebral junction patients with irreducible anterior compression.

BACKGROUND: Although the single-stage posterior realignment craniovertebral junction (CVJ) surgery could treat most of the basilar invagination (BI) and atlantoaxial dislocation (AAD), there are still some cases with incomplete decompression of the spinal cord, which remains a technique challenging situation. METHODS: Eleven patients were included with remained myelopathic symptoms after posterior correction due to incomplete decompression of the spinal cord. Transoral odontoidectomy assisted by image-guided navigation and intraoperative CT was performed. Clinical assessment and image measurements were performed preoperatively and at the most recent follow-up. RESULTS: Eleven patients were followed up for an average of 47 months. Symptoms were alleviated in 10 of 11 patients (90.9%). One patient died of an unknown reason 1 week after the transoral approach. The clinical and radiological parameters pre- and postoperatively were reported. CONCLUSION: Transoral odontoidectomy as a salvage surgery is safe and effective for properly selected BI and AAD patients after inadequate indirect decompression from posterior distraction and fixation. Image-guided navigation and intraoperative CT can provide precise information and accurate localization during operation, thus enabling complete resection of the odontoid process and decompression of the spinal cord.

Chronic extradural compression of spinal cord leads to syringomyelia in rat model.

BACKGROUND: Syringomyelia is a common spinal cord lesion. However, whether CSF blockage is linked to the formation and enlargement of syringomyelia is still controversial. The current model of syringomyelia needs modification to more closely mimic the clinical situation. METHODS: We placed cotton strips under the T13 lamina of 40 8-week-old rats and blocked CSF flow by extradural compression. After 4 and 8 weeks, MRI was performed to evaluate the morphology of syringomyelia and the ratio of spinal cord diameter to syrinx diameter calculated. Locomotor function was evaluated weekly. Spinal cord sections, staining and immunohistochemistry were performed 8 weeks after surgery, the ratio of the central canal to the spinal cord area was calculated, and ependymal cells were counted. In another experiment, we performed decompression surgery for 8 rats with induced syringomyelia at the 8th week after surgery. During the surgery, the cotton strip was completely removed without damaging the dura mater. Then, the rats received MRI imaging during the following weeks and were sacrificed for pathological examination at the end of the experiment. RESULTS: Syringomyelia formed in 82.5% (33/40) of rats at the 8-week follow-up. The Basso, Beattie and Bresnahan (BBB) scores of rats in the experimental group decreased from 21.0±0.0 to 18.0 ±3.9 in the first week after operation but returned to normal in later weeks. The BBB score indicated that the locomotor deficit caused by compression is temporary and can spontaneously recover. MRI showed that the syrinx is located in the center of the spinal cord, which is very similar to the most common syringomyelia in humans. The ratio of the central canal to the spinal cord area reached (2.9 ± 2.0) × 10-2, while that of the sham group was (5.4 ± 1.5) × 10-4. The number of ependymal cells lining the central canal was significantly increased (101.9 ± 39.6 vs 54.5 ± 3.4). There was no syrinx or proliferative inflammatory cells in the spinal cord parenchyma. After decompression, the syringomyelia size decreased in 50% (4/8) of the rats and increased in another 50% (4/8). CONCLUSION: Extradural blockade of CSF flow can induce syringomyelia in rats. Temporary locomotor deficit occurred in some rats. This reproducible rat model of syringomyelia, which mimics syringomyelia in humans, can provide a good model for the study of disease mechanisms and therapies.