Refining the treatment of spinal cord lesions: experience from 500 cases.

OBJECTIVE: Tumorous lesions of the spinal cord, as well as some vascular lesions like cavernous hemangiomas, demand careful consideration as to the indication and approach for surgery. As these lesions are rare in any departmental series, refinement of treatment strategies evolves over long periods. In this context, the authors evaluated a series of 500 intramedullary lesions for approach, technique, outcome, complications, and follow-up. METHODS: Five hundred intramedullary lesions in 460 patients were treated with a continuously evolving departmental strategy between 1985 and 2020. No lesions of the cauda equina or filum terminale were included. The focus of the evaluation was on the adaptation of exposure, resective methodology, sequelae, imaging, and rate of recurrence. Thirty-seven patients were children at the time of diagnosis. RESULTS: Among the 348 neoplastic lesions, the largest subtype was ependymoma (n = 192, 55.2%), followed by astrocytoma (n = 89, 25.6%). As a trend, metastases (n = 21) have become more frequent and more apparent only in the past 15 years. Reoperations for recurrent or progressive cases or referrals after incomplete resection were performed in 56 cases, mostly for progressive diffuse or pilocytic astrocytomas. Among the vascular lesions, 68 (54.8%) were hemangioblastomas, followed by 56 (45.2%) cavernous hemangiomas. All intramedullary tumors were approached through a midline myelotomy, refining an en bloc resection technique for endophytic tumors to increase the rate of radical resection. Cavernous hemangiomas reaching the surface and hemangioblastomas were approached directly. Complete removal was possible in 77.2% of endophytic tumors but in only 41.7% of diffuse tumors. All WHO grade II diffuse astrocytomas, WHO grade III tumors, and glioblastoma progressed despite treatment according to standard regimens. Vascular lesions were regularly removed completely, with only 1 recurrence of a large hemorrhagic thoracic cavernous hemangioma. The major sequelae were sensory deficits and neuropathic pain. Stabilizing instrumentation was placed in 5 cases of spinal deformity, mostly when more than 4 levels were affected, and in the pediatric population. CONCLUSIONS: In a large series of intramedullary surgeries, refinement of treatment strategies related to exposure, implementation of intraoperative adjuncts such as ultrasound, intraoperative neuromonitoring, resective strategies, and reconstruction were evaluated. The authors found that for almost any defined, endophytic medullary lesion, a safe and complete removal can be offered.

Intraoperative blood loss in oncological spine surgery.

OBJECTIVE: Intraoperative blood loss in patients undergoing oncological spine surgery poses a major challenge for vulnerable patients. The goal of this study was to assess how the surgical procedure, tumor type, and tumor anatomy, as well as anesthesiological parameters, affect intraoperative blood loss in oncological spine surgery and to use this information to generate a short preoperative checklist for spine surgeons and anesthesiologists to identify patients at risk for increased intraoperative blood loss. METHODS: The authors performed a retrospective analysis of 430 oncological patients who underwent spine surgery between 2013 and 2018 at the university medical spine center. Enrolled patients had metastatic tumor of the spine requiring surgical decompression of neural structures and/or stabilization including tumor biopsy using an open, percutaneous, and/or combined dorsoventral approach. Patients requiring vertebro- and kyphoplasty or biopsy only were excluded. Statistical analyses performed included a multiple linear regression analysis. RESULTS: The mean intraoperative blood loss in the study patient cohort was 1176 ± 1209 ml. In total, 33.8% of patients received intraoperative red blood cell transfusions. The statistical analyses showed that tumor histology indicating myeloma, operative procedure length, epidural spinal cord compression (ESCC) score, tumor localization, BMI, and surgical strategy were significantly associated with increased intraoperative blood loss or risk of needing allogeneic blood transfusions. Anesthesiological parameters such as the American Society of Anesthesiologists (ASA) Physical Status classification score were not associated with blood loss. Multiple linear regression analysis demonstrated good predictive value (r = 0.437) for a five-item preoperative checklist to identify patients at risk for high intraoperative blood loss. CONCLUSIONS: The analyses performed in this study demonstrated key factors affecting intraoperative blood loss and showed that a simple preoperative checklist including these factors can be used to identify patients undergoing surgery for metastatic spine tumors who are at risk for increased intraoperative blood loss. ABBREVIATIONS: ABT = allogeneic blood transfusion; ASA = American Society of Anesthesiologists; ESCC = epidural spinal cord compression; KW = Kruskal-Wallis; MET = metabolic equivalent of task; RBC = red blood cell.

Cranial bone flap resorption-pathological features and their implications for clinical treatment.

Cranioplasty following decompressive craniectomy (DC) has a primary complication when using the autologous bone: aseptic bone resorption (ABR). So far, risk factors such as age, number of fragments, and hydrocephalus have been identified but a thorough understanding of the underlying pathophysiology is still missing. The aim of this osteopathological investigation was to gain a better understanding of the underlying processes. Clinical data of patients who underwent surgical revision due to ABR was collected. Demographics, the time interval between craniectomy and cranioplasty, and endocrine serum parameters affecting bone metabolism were collected. Removed specimens underwent qualitative and quantitative histological examination. Two grafts without ABR were examined as controls. Compared to the controls, the typical layering of the cortical and cancellous bone was largely eliminated in the grafts. Histological investigations revealed the coexistence of osteolytic and osteoblastic activity within the necrosis. Bone appositions were distributed over the entire graft area. Remaining marrow spaces were predominantly fibrotic or necrotic. In areas with marrow cavity fibrosis, hardly any new bone tissue was found in the adjacent bone, while there were increased signs of osteoclastic resorption. Insufficient reintegration of the flap may be due to residual fatty bone marrow contained in the bone flap which seems to act as a barrier for osteogenesis. This may obstruct the reorganization of the bone structure, inducing aseptic bone necrosis. Following a path already taken in orthopedic surgery, thorough lavage of the implant to remove the bone marrow may be a possibility, but will need further investigation.

Carbon fiber-reinforced PEEK versus titanium implants: an in vitro comparison of susceptibility artifacts in CT and MR imaging.

Artifacts in computed tomography (CT) and magnetic resonance imaging (MRI) due to titanium implants in spine surgery are known to cause difficulties in follow-up imaging, radiation planning, and precise dose delivery in patients with spinal tumors. Carbon fiber-reinforced polyetheretherketon (CFRP) implants aim to reduce these artifacts. Our aim was to analyze susceptibility artifacts of these implants using a standardized in vitro model. Titanium and CFRP screw-rod phantoms were embedded in 3% agarose gel. Phantoms were scanned with Siemens Somatom AS Open and 3.0-T Siemens Skyra scanners. Regions of interest (ROIs) were plotted and analyzed for CT and MRI at clinically relevant localizations. CT voxel-based imaging analysis showed a significant difference of artifact intensity and central overlay between titanium and CFRP phantoms. For the virtual regions of the spinal canal, titanium implants (ti) presented - 30.7 HU vs. 33.4 HU mean for CFRP (p < 0.001), at the posterior margin of the vertebral body 68.9 HU (ti) vs. 59.8 HU (CFRP) (p < 0.001) and at the anterior part of the vertebral body 201.2 HU (ti) vs. 70.4 HU (CFRP) (p < 0.001), respectively. MRI data was only visually interpreted due to the low sample size and lack of an objective measuring system as Hounsfield units in CT. CT imaging of the phantom with typical implant configuration for thoracic stabilization could demonstrate a significant artifact reduction in CFRP implants compared with titanium implants for evaluation of index structures. Radiolucency with less artifacts provides a better interpretation of follow-up imaging, radiation planning, and more precise dose delivery.

Surgical treatment and neurological outcome of infiltrating intramedullary astrocytoma WHO II-IV: a multicenter retrospective case series.

INTRODUCTION: Primary malignant spinal astrocytomas present rare oncological entities with limited median survival and rapid neurological deterioration. Evidence on surgical therapy, adjuvant treatment, and neurological outcome is sparse. We aim to describe the treatment algorithm and clinical features on patients with infiltrating intramedullary astrocytomas graded WHO II-IV. METHODS: The following is a multicentered retrospective study of patients treated for spinal malignant glioma WHO II-IV in five high-volume neurosurgical departments from 2008 to 2019. Pilocytic astrocytomas were excluded. We assessed data on surgical technique, perioperative neurological status, adjuvant oncological therapy, and clinical outcome. RESULTS: 40 patients were included (diffuse astrocytoma WHO II n = 11, anaplastic astrocytoma WHO III n = 12, WHO IV n = 17). Only 40% were functionally independent before surgery, most patients presented with moderate disability (47.5%). Most patients underwent a biopsy (n = 18, 45%) or subtotal tumor resection (n = 15, 37.5%), and 49% of the patients deteriorated after surgery. Patients with WHO III and IV tumors were treated with combined radiochemotherapy. Median overall survival (OS) was 46.5 months in WHO II, 25.7 months in WHO III, and 7.4 months in WHO IV astrocytomas. Preoperative clinical status and WHO significantly influenced the OS, and the extent of resection did not. CONCLUSION: Infiltrating intramedullary astrocytomas WHO II-IV present rare entities with dismal prognosis. Due to the high incidence of surgery-related neurological impairment, the aim of the surgical approach should be limited to obtaining the histological tissue via a biopsy or, tumor debulking in cases with rapidly progressive severe preoperative deficits.

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes.

Purpose: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T cells (tumor-infiltrating lymphocytes; TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion.Experimental Design: We used flow cytometry and cytokine assays to profile TILs and peripheral blood lymphocytes (PBLs) from patients with GBM, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed on paired samples of newly diagnosed and recurrent GBM.Results: We identified a clear immune signature of exhaustion and clonal restriction in the TILs of patients with GBM. Exhaustion of CD8+ TILs was defined by an increased prevalence of PD-1+, CD39+, Tim-3+, CD45RO+, HLA-DR+ marker expression, and exhibition of an effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57 were underrepresented. Immune signatures were similar in primary and recurrent tumors; however, restricted TCR repertoire clonality and a more activated memory phenotype were observed in TILs from recurrent tumors. Moreover, a reduced cytokine response to PHA stimulation in the blood compartment indicates a dysfunctional peripheral T-cell response in patients with GBM. LTS displayed a distinct profile, with abundant naïve and less exhausted CD8+ T cells.Conclusions: TILs and PBLs exhibit contrasting immune profiles, with a distinct exhaustion signature present in TILs. While the exhaustion profiles of primary and recurrent GBM are comparable, TCR sequencing demonstrated a contracted repertoire in recurrent GBM, concomitant with an increased frequency of activated memory T cells in recurrent tumors. Clin Cancer Res; 24(17); 4187-200. ©2018 AACRSee related commentary by Jackson and Lim, p. 4059.

Impact of the surgical strategy on the incidence of C5 nerve root palsy in decompressive cervical surgery.

OBJECTIVE: Our aim was to identify the impact of different surgical strategies on the incidence of C5 palsy. BACKGROUND: Degenerative cervical spinal stenosis is a steadily increasing morbidity in the ageing population. Postoperative C5 nerve root palsy is a common complication with severe impact on the patients´ quality of life. METHODS: We identified 1708 consecutive patients who underwent cervical decompression surgery due to degenerative changes. The incidence of C5 palsy and surgical parameters including type and level of surgery were recorded to identify predictors for C5 nerve palsy. RESULTS: The overall C5 palsy rate was 4.8%, with 18.3% of cases being bilateral. For ACDF alone the palsy rate was low (1.13%), compared to 14.0% of C5 palsy rate after corpectomy. The risk increased with extension of the procedures. Hybrid constructs with corpectomy plus ACDF at C3-6 showed significantly lower rates of C5 palsy (10.7%) than corpectomy of two vertebrae (p = 0.005). Multiple regression analysis identified corpectomy of C4 or C5 as a significant predictor. We observed a lower overall incidence for ventral (4.3%) compared to dorsal (10.9%) approaches (p<0.001). When imaging detected a postoperative shift of the spinal cord at index segment C4/5, palsy rate increased significantly (33.3% vs. 12.5%, p = 0.034). CONCLUSIONS: Extended surgical strategies, such as dorsal laminectomies, multilevel corpectomies and procedures with extensive spinal cord shift were shown to display a high risk of C5 palsy. The use of extended procedures should therefore be employed cautiously. Switching to combined surgical methods like ACDF plus corpectomy can reduce the rate of C5 palsy.

Cervical vertebroplasty for osteolytic metastases as a minimally invasive therapeutic option in oncological surgery: outcome in 14 cases.

OBJECTIVE The treatment of cervical spinal metastases represents a controversial issue regarding the type, extent, and invasiveness of interventions. In the lumbar and thoracic spine, kypho- and vertebroplasties have been established as minimally invasive procedures for patients with metastases to the vertebral bodies and without neurological deficit. These procedures show good results with respect to pain reduction and low complication rates. However, limited data are available for kypho- and vertebroplasties for cervical spinal metastases. In an effort to add to existing data, the authors here present a case series of 14 patients who were treated for osteolytic metastases of the cervical spine using vertebroplasty alone or in addition to another surgical procedure involving the cervical spine in a palliative setting to reduce pain and restore stability. METHODS Fourteen patients consisting of 8 males and 6 females, with a mean age of 64.7 years (range 44-85 years), were treated with vertebroplasty at the authors' clinic between January 2015 and November 2016. In total, 25 vertebrae were treated with vertebroplasty: 10 C-2, 5 C-3, 2 C-4, 2 C-5, 3 C-6, and 3 C-7. Two patients had an additional posterior stabilization and 5 patients an additional anterior stabilization. In 13 cases, the surgical approach was a modified Smith-Robinson approach; in 1 case, the cement was injected into the corpus axis from posteriorly. Patients with osteolytic defects of the posterior wall of the vertebral body did not undergo surgery, nor did patients with neurological deficits. Preoperatively, on the 2nd day after surgery, and at the follow-up, neck pain was rated using the visual analog scale (VAS). RESULTS Twelve patients were examined at follow-up (mean 9 months). Neck pain was rated as a mean of 6.0 (range 3-8) preoperatively, 2.9 on Day 2 after surgery (range 0-5), and 0.5 at the follow-up (range 0-4), according to the VAS. The mean Neck Disability Index at follow-up was 3.6% (range 0%-18%). CONCLUSIONS Anterior vertebroplasty of the cervical spine via an anterolateral approach represents a safe and minimally invasive procedure with a low complication rate and appears suitable for reducing pain and restoring stability in cases of cervical spinal metastases. Vertebroplasties can be combined with other anterior and posterior operations of the cervical spine and, in the axis vertebra, can be performed transpedicularly from posteriorly. Thus, in cases in which the posterior wall of the vertebral body is intact, vertebroplasty represents a less invasive alternative to vertebral replacement in oncological surgery. Prospective randomized trials with a longer follow-up period and a larger patient cohort are needed to confirm the encouraging results of this case series.

Keyhole approaches to intradural pathologies.

OBJECTIVE Spinal tumors account for 2%-4% of all tumors of the central nervous system and can be intramedullary, intradural extramedullary, or extradural. In the past, wide approaches were used to obtain safe access to these tumors, as complete resection is the goal in treating most tumor entities. To reduce surgical complications due to large skin incisions and destabilizing laminectomies, minimally invasive approaches were established. In this study, the authors share their experience with mini-open approaches to intradural tumor pathologies. METHODS The authors retrospectively reviewed cases involving patients with intramedullary and intradural extramedullary lesions treated between 2009 and 2016. They present their surgical mini-open approach to the spinal cord as well as unique characteristics, key steps, and postsurgical complications for specific tumor subgroups (meningioma, neuroma, and intramedullary tumors). RESULTS A total of 245 intradural tumors were surgically treated during the study period. Of these lesions, 151 were intradural extramedullary meningiomas (n = 79) or neuromas (n = 72). Nine (12.5%) of the neuromas were dumbbell neuromas. Ninety-four tumors were intramedullary. The mean age of the patients was 51.4 years, and 53.9% were female. The mean duration of follow-up was 46.0 months. All meningiomas and neuromas could be resected using a mini-open keyhole approach, but only 5.3% of the intramedullary lesions could be accessed using this technique. Of the 94 patients with intramedullary tumors, 76.6% required a laminotomy, 7.4% required a hemilaminectomy, and 10.6% required a 2-level laminectomy. Only 2 of the patients with intramedullary tumors needed stabilization for progressive cervical kyphosis during follow-up. None of the other patients developed spinal instability after undergoing surgery via the mini-open (keyhole/interlaminar) approach. There were significantly more surgery-associated complications in the large exposure group than in the patients treated with the mini-open approach (19.1% vs 9.6%, p < 0.01). CONCLUSIONS Intradural extramedullary and in selected cases intramedullary pathologies may safely be resected using a mini-open interlaminar approach. Avoiding laminectomy, laminotomy, and even hemilaminectomy preserves spinal stability and significantly reduces comorbidities, while still allowing for complete resection of these tumors.

Validation of the modified Graeb score in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is a known negative predictor. Scoring systems like Fisher, Le Roux, and original Graeb score (oGS) are established to quantify the volume of IVH. The aim of this study was to evaluate the validity of the recently introduced modified Graeb score (mGS) in patients with aSAH. METHODS: A retrospective analysis of the validity of the oGS and mGS in 257 aSAH patients was performed to assess and compare the predictive value of hospital mortality, development of CHC, and early functional outcome. RESULTS: In univariate analysis, an increase in either the oGS or mGS was associated with a higher risk for hospital mortality, development of CHC, and poor early functional outcome. The correlation of the oGS and mGS was excellent using Pearson's product-moment (r = 0.918; p < 0.001). The predictive value of the oGS was superior to the predictive value of the mGS using receiver operating characteristics and corresponding area under the curve value as there was no statistical significant differences between the scores. CONCLUSIONS: Our study confirms the validity of the recently introduced mGS to quantify the volume of IVH and extends its value in aSAH. However, the mGS offers no additional predictive value for hospital mortality, development of CHC, and poor early functional outcome in patients with aSAH patients compared to the less complex oGS.