GNA14 and GNAQ somatic mutations cause spinal and intracranial extra-axial cavernous hemangiomas.

Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both in vitro and in vivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.

Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma.

BACKGROUND: Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma. METHODS: Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-ß scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model. RESULTS: Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-ß as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-ß scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-ß scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells. CONCLUSIONS: This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-ß in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-ß signalling, may augment the efficacy of CAR-T cells.

IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve.

BACKGROUND: The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure. METHODS: A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION's CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain. RESULTS: CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION's CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION's CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION. CONCLUSION: IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions.

Mutational landscape of primary spinal cord astrocytoma.

Primary spinal cord astrocytoma (SCA) is a rare disease. Knowledge about the molecular profiles of SCAs mostly comes from intracranial glioma; the pattern of genetic alterations of SCAs is not well understood. Herein, we describe genome-sequencing analyses of primary SCAs, aiming to characterize the mutational landscape of primary SCAs. We utilized whole exome sequencing (WES) to analyze somatic nucleotide variants (SNVs) and copy number variants (CNVs) among 51 primary SCAs. Driver genes were searched using four algorithms. GISTIC2 was used to detect significant CNVs. Additionally, recurrently mutated pathways were also summarized. A total of 12 driver genes were identified. Of those, H3F3A (47.1%), TP53 (29.4%), NF1 (19.6%), ATRX (17.6%), and PPM1D (17.6%) were the most frequently mutated genes. Furthermore, three novel driver genes seldom reported in glioma were identified: HNRNPC, SYNE1, and RBM10. Several germline mutations, including three variants (SLC16A8 rs2235573, LMF1 rs3751667, FAM20C rs774848096) that were associated with risk of brain glioma, were frequently observed in SCAs. Moreover, 12q14.1 (13.7%) encompassing the oncogene CDK4 was recurrently amplified and negatively affected patient prognosis. Besides frequently mutated RTK/RAS pathway and PI3K pathway, the cell cycle pathway controlling the phosphorylation of retinoblastoma protein (RB) was mutated in 39.2% of patients. Overall, a considerable degree of the somatic mutation landscape is shared between SCAs and brainstem glioma. Our work provides a key insight into the molecular profiling of primary SCAs, which might represent candidate drug targets and complement the molecular atlas of glioma. © 2023 The Pathological Society of Great Britain and Ireland.

Posterior intra-articular distraction technique to treat pediatric atlantoaxial instability.

PURPOSE: Surgical treatment for atlantoaxial instability in pediatric patients is challenging. We report our experience with posterior intra-articular distraction technique in treating this disorder. METHODS: This is a retrospective descriptive study which included 15 patients of atlantoaxial instability whose age was less than 16 years at the time of clinical presentation. All patients underwent anterior soft tissue released through a posterior-only approach, followed by intra-facet cage implantation, cantilever correction, and instrumentation. Clinical results were measured using the Japanese Orthopedic Association (JOA) scale and radiographic measurements including the atlantodental interval (ADI), posterior atlantodental interval (pADI), the distance of odontoid tip above Chamberlain's line, clivuscanal angle (CCA), and triangular area (TA) of craniovertebral junction. RESULTS: The follow-up period ranged from 18 to 72 months, with an average of 41.2 ± 15.2 months. The JOA score increased from 13.6 ± 2.3 to 16.6 ± 0.8. ADI decreased from 4.31 ± 2.37 to 1.85 ± 1.09 mm, and TA decreased from 261.96 ± 107.99 to 197.12 ± 72.37 mm2. pADI increased from 12.89 ± 3.52 to 18.25 ± 3.89 mm, and CCA improved from 132.19 ± 16.34 to 144.35 ± 13.91°. All changes in measurements showed statistically significant. There were no evidence of surgery-related complications or iatrogenic secondary cervical deformity during follow-up. Radiological evaluation showed satisfactory corrections and bony fusions of C1-2 facet joint in all cases. CONCLUSION: Posterior intra-articular distraction followed by cage implantation and cantilever correction can be one of the safe and effective ways to solve atlantoaxial instability in pediatric patients.

Steering Toward Normative Wide-Dynamic-Range Neuron Activity in Nerve-Injured Rats With Closed-Loop Peripheral Nerve Stimulation.

OBJECTIVES: Chronic pain is primarily treated with pharmaceuticals, but the effects remain unsatisfactory. A promising alternative therapy is peripheral nerve stimulation (PNS), but it has been associated with suboptimal efficacy because its modulation mechanisms are not clear and the current therapies are primarily open loop (ie, manually adjusting the stimulation parameters). In this study, we developed a proof-of-concept computational modeling as the first step toward implementing closed-loop PNS in future biological studies. When developing new pain therapies, a useful pain biomarker is the wide-dynamic-range (WDR) neuron activity in the dorsal horn. In healthy animals, the WDR neuron activity occurs in a stereotyped manner; however, this response profile can vary widely after nerve injury to create a chronic pain condition. We hypothesized that if injury-induced changes of neuronal response can be normalized to resemble those of a healthy condition, the pathological aspects of pain may be treated while maintaining protective physiological nociception. MATERIALS AND METHODS: Using an in vivo electrophysiology data set of WDR neuron recordings obtained in nerve-injured rats and naïve rats, we constructed sets of linear phenomenologic models of WDR firing rate during windup stimulation for both conditions. Then, we applied robust control systems techniques to identify a closed-loop PNS controller, which can drive the dynamics of WDR neuron response in neuropathic pain model into ranges associated with normal physiological pain. RESULTS: The sets of identified linear models can accurately predict, in silico, nonlinear neural responses to electrical stimulation of the peripheral nerve. In addition, we showed that continuous closed-loop control of PNS can be used to normalize WDR neuron firing responses in three injured cases. CONCLUSIONS: In this proof-of-concept study, we show how tractable, linear mathematical models of pain-related neurotransmission can be used to inform the development of closed-loop PNS. This new application of robust control to neurotechnology may also be expanded and applied across other neuromodulation applications.

Single-cell transcriptome profiling reveals intra-tumoral heterogeneity in human chordomas.

Chordoma is a rare and aggressive bone tumor. An accurate investigation of tumor heterogeneity is necessary for the development of effective therapeutic strategies. This study aims to assess the poorly understood tumor heterogeneity of chordomas and identify potential therapeutic targets. Single-cell RNA sequencing was performed to delineate the transcriptomic landscape of chordomas. Six tumor samples of chordomas were obtained, and 33,737 cells passed the quality control test and were analyzed. The main cellular populations identified with specific markers were as follows: chordoma cells (16,052 [47.6%]), fibroblasts (6945 [20.6%]), mononuclear phagocytes (4734 [14.0%]), and T/natural killer (NK) cells (3944 [11.7%]). Downstream analysis of each cell type was performed. Six subclusters of chordomas exhibited properties of an epithelial-like extracellular matrix, stem cells, and immunosuppressive activity. Although few immune checkpoints were detected on cytotoxic immune cells such as T and NK cells, a strong immunosuppressive effect was exerted on the Tregs and M2 macrophages. In addition, the cellular interactions were indicative of enhancement of the TGF-ß signaling pathway being the main mechanism for tumor progression, invasion, and immunosuppression. These findings, especially from the analysis of molecular targeted therapy and tumor immune microenvironment, may help in the identification of therapeutic targets in chordomas.

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.

Dural ossification associated with ossification of posterior longitudinal ligament in the cervical spine: a retrospective analysis.

OBJECTIVE: Dural ossification (DO) is common in patients with ossification of the posterior longitudinal ligament (OPLL). The existence of DO makes surgery challenging and increases the risk of complications. The aim of this study was to investigate the incidence, distribution and radiological characteristics of DO associated with OPLL. METHODS: From January 2017 to January 2019, 55 patients with cervical OPLL were treated in our single center using an anterior cervical approach microsurgery. Preoperative CT images of decompressed segments were evaluated to identify imaging signs of DO. The 'double-layer sign' (DLS), 'parenthese sign' (PS) and 'hook sign' (HS) were considered to be characteristic imaging findings of DO in OPLL. Two kinds of confusing signs (false double-layer) were identified. RESULTS: Nineteen segments from 15 patients with OPLL had DO related to OPLL. The incidence of DO in OPLL segments was 30.16% (19/63), and the incidence of DO in patients with OPLL was 27.27% (15/55). DO occurred at the intervertebral space level in 14 cases and at the posterior level of the vertebral body in 5 cases. The sensitivity and specificity of imaging diagnosis were 89.47% (17/19) and 81.82% (36/44), respectively. The positive predictive value was relatively low, 68.00% (17/25), due to the false-positive double-layer sign. The negative predictive value was 94.74% (36/38). CONCLUSION: DO was relatively common in cervical OPLL. DLS might be misdiagnosed. PS and HS can vividly and intuitively describe the imaging features of DO and have high diagnostic accuracy.

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.

Spinal Cord Stimulation Attenuates Below-Level Mechanical Hypersensitivity in Rats After Thoracic Spinal Cord Injury.

OBJECTIVES: The burden of pain after spinal cord injury (SCI), which may occur above, at, or below injury level, is high worldwide. Spinal cord stimulation (SCS) is an important neuromodulation pain therapy, but its efficacy in SCI pain remains unclear. In SCI rats, we tested whether conventional SCS (50 Hz, 80% motor threshold [MoT]) and 1200 Hz, low-intensity SCS (40% MoT) inhibit hind paw mechanical hypersensitivity, and whether conventional SCS attenuates evoked responses of wide-dynamic range (WDR) neurons in lumbar spinal cord. MATERIALS AND METHODS: Male rats underwent a moderate contusive injury at the T9 vertebral level. Six to eight weeks later, SCS or sham stimulation (120 min, n = 10) was delivered through epidural miniature electrodes placed at upper-lumbar spinal cord, with using a crossover design. Mechanical hypersensitivity was examined in awake rats by measuring paw withdrawal threshold (PWT) to stimulation with von Frey filaments. WDR neurons were recorded with in vivo electrophysiologic methods in a separate study of anesthetized rats. RESULTS: Both conventional SCS and 1200 Hz SCS increased PWTs from prestimulation level in SCI rats, but the effects were modest and short-lived. Sham SCS was not effective. Conventional SCS (10 min) at an intensity that evokes the peak Aα/ß waveform of sciatic compound action potential did not inhibit WDR neuronal responses (n = 19) to graded or repeated electrical stimulation that induces windup. CONCLUSIONS: Conventional SCS and 1200 Hz, low-intensity SCS modestly attenuated below-level mechanical hypersensitivity after SCI. Inhibition of WDR neurons was not associated with pain inhibition from conventional SCS.

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.

Predictors of mortality in patients with primary spinal cord glioblastoma.

PURPOSE: Primary spinal cord glioblastoma (GBM) is a rare and devastating disease. Little attention was ever paid to this rare disease. As a result, the standard treatment protocol and prognostic factors of primary spinal cord GBM were not well established. The aim of this study was to determine the predictors associated with survival in patients with primary spinal cord GBM. METHODS: A total of 122 patients with primary spinal cord GBM from Surveillance, Epidemiology, and End Results database and our institution were included in this retrospective analysis. Information about age, sex, race, tumor invasion, extent of resection, radiation, chemotherapy and year of diagnosis was collected. Univariate and multivariate accelerated failure time (AFT) regression model was performed to identify prognostic factors. RESULTS: Of the 122 patients, 102 (83.6%) expired at the time of data collection. Overall survival at 1 year, 2 years, 3 years and 5 years was 48.4%, 22.8%, 17.1% and 8.4%, respectively, and median survival time was 12 months. Only radiation was found to be associated with survival in the AFT regression model (time ratio 1.94, 95% CI 1.01-3.72, p < 0.05). Radiotherapy could improve survival slightly; patients who received RT survived approximately two times as long as patients who did not receive RT, but the advantage was short term. CONCLUSION: The survival of primary spinal cord GBM is poor in the current treatment strategy. Radiotherapy was associated with better survival, but the advantage was short term.

Modulation of Spinal Nociceptive Transmission by Sub-Sensory Threshold Spinal Cord Stimulation in Rats After Nerve Injury.

OBJECTIVES: High-frequency spinal cord stimulation (SCS) administered below the sensory threshold (subparesthetic) can inhibit pain, but the mechanisms remain obscure. We examined how different SCS paradigms applied at intensities below the threshold of Aß-fiber activation (sub-sensory threshold) affect spinal nociceptive transmission in rats after an L5 spinal nerve ligation (SNL). MATERIALS AND METHODS: Electrophysiology was used to record local field potential (LFP) at L4 spinal cord before, during, and 0-60 min after SCS in SNL rats. LFP was evoked by high-intensity paired-pulse test stimulation (5 mA, 0.2 msec, 400 msec interval) at the sciatic nerve. Epidural SCS was delivered through a miniature electrode placed at T13-L1 and L2-L3 spinal levels. Four patterns of SCS (200 Hz, 1 msec; 500 Hz, 0.5 msec; 1200 Hz; 0.2 msec; 10,000 Hz, 0.024 msec, 30 min, bipolar) were tested at 90% Aß-threshold as a subthreshold intensity. As a positive control, traditional SCS (50 Hz, 0.2 msec) was tested at 100% Aß-plateau as a suprathreshold intensity. RESULTS: Traditional suprathreshold SCS at T13-L1 level significantly reduced LFP to C-fiber inputs (C-LFP). Subthreshold SCS of 200 and 500 Hz, but not 1200 or 10,000 Hz, also reduced C-LFP, albeit to a lesser extent than did traditional SCS (n = 7-10/group). When SCS was applied at the L2-L3 level, only traditional SCS and subthreshold SCS of 200 Hz inhibited C-LFP (n = 8-10/group). CONCLUSIONS: Traditional suprathreshold SCS acutely inhibits spinal nociceptive transmission. Low-frequency subthreshold SCS with a long pulse width (200 Hz, 1 msec), but not higher-frequency SCS, also attenuates C-LFP.

Effectiveness of posterior reduction and fixation in atlantoaxial dislocation: a retrospective cohort study of 135 patients with a treatment algorithm proposal.

PURPOSE: Surgical procedures on atlantoaxial dislocation remain controversial. The aim of this observational retrospective study was to investigate the treatment algorithm of surgical procedures. METHODS: According to CT and intraoperative evaluation during direct posterior reduction, 135 AAD cases were categorized into three groups: Group I: reducible dislocation; Group II: irreducible dislocation (Group IIa: effective decompression achieved after posterior reduction; Group IIb: no effective decompression after posterior reduction); and Group III: fixed dislocation. Group III presented with extensive bony fusions. Group I and Group IIa were treated with direct posterior reduction and fixation. Group IIb underwent posterior fixation and transoral odontoidectomy. Group III underwent transoral odontoidectomy alone. Japanese Orthopedic Association scores (JOA) were assessed to evaluate clinical status before and 6, 12 months after surgery. RESULTS: Our study included 118 Group I cases, 16 Group II cases (Group IIa: 11 cases; Group IIb: 5 cases), and one Group III case. Follow-up ranged from 12 to 36 months. PRIMARY OUTCOME: Anatomic atlantoaxial reduction was achieved in 118 of 135 patients (87.4%). Clinical improvements were seen in 96.3% (130/135) all the patients. Solid atlantoaxial fusion was shown in 134 patients. Secondary outcome: The overall complication rate was 3.7% (5/135). For Group I, the mean postoperative 6-month JOA was 14.5 versus 12.2 in preoperative patients (paired Student's t test, P < 0.01). CONCLUSIONS: This article proposes a clinical procedure that assists with therapeutic decision making and indicates the severity and difficulty of reduction of the atlantoaxial joint. These slides can be retrieved under Electronic Supplementary Material.

Carotid Artery-Related Perioperative Stroke Following Anterior Cervical Spine Surgery: A Series of 3 Cases and Literature Review.

BACKGROUND: Vascular complications following anterior cervical spine surgery are rare but potentially devastating. Complications associated with the carotid artery are even more disastrous but largely anecdotal, with no more than 4 reported cases. MATERIALS AND METHODS: We report 3 new cases of carotid artery-related perioperative stroke following anterior cervical spine surgery. All 3 patients had carotid artery atherosclerosis and the time of intraoperative carotid artery retraction was longer than 1 hour. One patient underwent hypotension during surgery. Risk factors as well as prevention and management protocols of carotid artery-related perioperative stroke based on the literature review and our clinical experience are discussed. CONCLUSIONS: Carotid artery-related perioperative stroke following anterior cervical spine surgery is extremely rare. Prolonged traction, carotid artery atherosclerosis, and intraoperative hypotension can produce cerebral hypoperfusion and cause ischemic stroke. Preoperative risk assessment, adequate perioperative manipulation, and postoperative management can minimize overall morbidity and mortality.

Diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria.

The aim of the study is to explore the experiences in diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria (G-). Nineteen patients with pyogenic ventriculitis were reviewed for their treatment. The bacterial testing results of cerebrospinal fluid (CSF), the clinical intervention, and the patients' prognosis were evaluated. The bacterial smears of ventricular drainage from all the cases were G- bacteria. Head CT and MRI scans confirmed that they were intraventricular empyema. Eighteen cases of CSF bacterial test were positive, including 12 cases of Acinetobacter baumannii positive, 2 of Klebsiella pneumonia positive, 2 of Serratia marcescens positive, 1 of Pseudomonas maltophila positive, and 1 case of Escherichia coli positive. One case of the bacterial culture was negative. All patients were treated by using intraventricular lavage in combination with intravenous and intraventricular antibiotics in accordance with the clinical conditions. After treatment for 2 to 8 weeks, 14 patients were cured (74%) and 5 were died (26%). Eight patients who were cured had received ventriculoperitoneal shunt due to hydrocephalus at 2 to 6 weeks after infection controlled, and none of them had any reinfection. Twelve of the 14 cured cases came to consciousness, but 2 were persistent in vegetative state starting before the infection; they did not show any improving consciousness after infection had been cured. Suppurative ventriculitis in severe neurosurgical patients is mainly infected by G- with a higher mortality. Early diagnosis, especially in identifying pathogen types, timely ventricular irrigation, and ventricular drainage together with intravenous and intraventricular antibiotic treatment, should improve prognosis.

Is anterior release and cervical traction necessary for the treatment of irreducible atlantoaxial dislocation? A systematic review and meta-analysis.

PURPOSE: To compare the clinical and radiographic outcomes of irreducible atlantoaxial dislocation (IAAD) treated with posterior fusion after anterior release and direct posterior reduction of the dislocation. METHODS: Online databases were searched for articles describing IAAD published from 1999 to 2015. Five studies (105 patients) described treatment with posterior fusion after periodontoid tissue release, and five studies (113 patients) described treatment with direct posterior reduction of the dislocation. The primary outcomes in this study were the complete reduction rate, Japanese Orthopedic Association score, perioperative morbidity, perioperative mortality, complications, vascular injury, and infection. Standard meta-analysis techniques were used to compare the outcomes. RESULTS: Of 319 citations examined, 10 articles involving 218 participants were eligible. Overall, there were no significant differences between the anterior release and posterior fixation (ARPF) group and direct posterior reduction and fixation (DPRF) group in the complete reduction rate, neurologic recovery rate, perioperative morbidity, perioperative mortality, vascular injury, or infection. However, the complication rate in the DPRF group was much lower than that in the ARPF group. CONCLUSIONS: Compared with posterior fusion after anterior release, direct posterior reduction of the dislocation showed no significant differences in terms of the complete reduction rate, neurologic recovery rate, or fusion rate; however, it was a simpler process associated with less surgical trauma and a shorter operation time. Because of the limitations of the small sample in this study, whether direct posterior reduction of the dislocation is more effective and safer than posterior fusion after anterior release remains unclear. LEVEL OF EVIDENCE: III. These slides can be retrieved under Electronic Supplementary Material.

Modulation of C-nociceptive Activities by Inputs from Myelinated Fibers.

To understand the mechanisms of neuropathic pain caused by demyelination, a rapid-onset, completed but reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by single injection of cobra venom into the sciatic nerve, was created. Microfilament recording revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. Neuropathic pain behaviors including inflammatory response appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evans blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field.