Preoperative Performance Status Threshold for Favorable Surgical Outcome in Metastatic Spine Disease.

BACKGROUND AND OBJECTIVES: Surgical treatment is an integral component of multimodality management of metastatic spine disease but must be balanced against the risk of surgery-related morbidity and mortality, making tailored surgical counseling a clinical challenge. The aim of this study was to investigate the potential predictive value of the preoperative performance status for surgical outcome in patients with spinal metastases. METHODS: Performance status was determined using the Karnofsky Performance Scale (KPS), and surgical outcome was classified as "favorable" or "unfavorable" based on postoperative changes in neurological function and perioperative complications. The correlation between preoperative performance status and surgical outcome was assessed to determine a KPS-related performance threshold. RESULTS: A total of 463 patients were included. The mean age was 63 years (range: 22-87), and the mean preoperative KPS was 70 (range: 30-100). Analysis of clinical outcome in relation to the preoperative performance status revealed a KPS threshold between 40% and 50% with a relative risk of an unfavorable outcome of 65.7% in KPS ≤40% compared with the relative chance for a favorable outcome of 77.1% in KPS ≥50%. Accordingly, we found significantly higher rates of preserved or restored ambulatory function in KPS ≥50% (85.7%) than in KPS ≤40% (48.6%; P < .001) as opposed to a significantly higher risk of perioperative mortality in KPS ≤40% (11.4%) than in KPS ≥50% (2.1%, P = .012). CONCLUSION: Our results underline the predictive value of the KPS in metastatic spine patients for counseling and decision-making. The study suggests an overall clinical benefit of surgical treatment of spinal metastases in patients with a preoperative KPS score ≥50%, while a high risk of unfavorable outcome outweighing the potential clinical benefit from surgery is encountered in patients with a KPS score ≤40%.

Local Recurrence and Development of Spinal Cord Syndrome during Follow-Up after Surgical Treatment of Metastatic Spine Disease.

BACKGROUND: Surgical decompression (SD), with or without posterior stabilization followed by radiotherapy, is an established treatment for patients with metastatic spinal disease with epidural spinal cord compression (ESCC). This study aims to identify risk factors for occurrence of neurological compromise resulting from local recurrence. METHODS: All patients who received surgical treatment for metastatic spinal disease at our center between 2011 and 2022 were included in this study. Cases were evaluated for tumor entity, surgical technique for decompression (decompression, hemilaminectomy, laminectomy, corpectomy) neurological deficits, grade of ESCC, time interval to radiotherapy, and perioperative complications. RESULTS: A total of 747 patients were included in the final analysis, with a follow-up of 296.8 days (95% CI (263.5, 330.1)). During the follow-up period, 7.5% of the patients developed spinal cord/cauda syndrome (SCS). Multivariate analysis revealed prolonged time (>35 d) to radiation therapy as a solitary risk factor (p < 0.001) for occurrence of SCS during follow-up. CONCLUSION: Surgical treatment of spinal metastatic disease improves patients' quality of life and Frankel grade, but radiation therapy needs to be scheduled within a time frame of a few weeks in order to reduce the risk of tumor-induced neurological compromise.

Role of Decompressive Surgery in Neurologically Intact Patients with Low to Intermediate Intraspinal Metastatic Tumor Burden.

BACKGROUND: Surgical decompression (SD) followed by radiotherapy (RT) is superior to RT alone in patients with metastatic spinal disease with epidural spinal cord compression (ESCC) and neurological deficit. For patients without neurological deficit and low- to intermediate-grade intraspinal tumor burden, data on whether SD is beneficial are scarce. This study aims to investigate the neurological outcome of patients without neurological deficit, with a low- to intermediate-ESCC, who were treated with or without SD. METHODS: This single-center, multidepartment retrospective analysis includes patients treated for spinal epidural metastases from 2011 to 2021. Neurological status was assessed by Frankel grade, and intraspinal tumor burden was categorized according to the ESCC scale. Spinal instrumentation surgery was only considered as SD if targeted decompression was performed. RESULTS: ESCC scale was determined in 519 patients. Of these, 190 (36.6%) presented with no neurological deficit and a low- to intermediate-grade ESCC (1b, 1c, or 2). Of these, 147 (77.4% were treated with decompression and 43 (22.65%) without. At last follow-up, there was no difference in neurological outcome between the two groups. CONCLUSIONS: Indication for decompressive surgery in neurologically intact patients with low-grade ESCC needs to be set cautiously. So far, it is unclear which patients benefit from additional decompressive surgery, warranting further prospective, randomized trials for this significant cohort of patients.

Brain abscess with Ureaplasma parvum in a patient with granulomatosis with polyangiitis.

PURPOSE: Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA). METHODS: Imaging and laboratory findings, treatment decisions, and outcome of this case are explicated. RESULTS: A young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive for Ureaplasma parvum. The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline. CONCLUSION: Ureaplasma species are rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes.

Cerebrospinal fluid leaks following intradural spinal surgery-Risk factors and clinical management.

Background: Cerebrospinal fluid leakage (CSFL) following spinal durotomy can lead to severe sequelae. However, while several studies have investigated accidental spinal durotomies, the risk factors and influence of clinical management in planned durotomies remain unclear. Methods: We performed a retrospective analysis of all patients who underwent planned intradural spinal surgery at our institution between 2010 and 2020. Depending on the occurrence of a CSFL, patients were dichotomized and compared with respect to patient and case-related variables as well as dural closure technique, epidural drainage placement, and timing of mobilization. Results: A total of 351 patients were included. CSFL occurred in 4.8% of all cases. Surgical indication, tumor histology, location within the spine, previous intradural surgery, and medical comorbidities were not associated with an increased risk of CSFL development (all p > 0.1). Age [odds ratio (OR), 0.335; 95% confidence interval (CI), 0.105-1.066] and gender (OR, 0.350; 95% CI, 0.110-1.115) were not independently associated with CSFL development. There was no significant association between CSFL development and the dural closure technique (p = 0.251), timing of mobilization (p = 0.332), or placement of an epidural drainage (p = 0.321). Conclusion: CSFL following planned durotomy pose a relevant and quantifiable complication risk of surgery that should be factored in during preoperative patient counseling. Our data could not demonstrate superiority of any particular dural closure technique but support the safety of both early mobilization within 24 h postoperatively and epidural drainage with reduced or no force of suction.

Impact of Spinal Instrumentation on Neurological Outcome in Patients with Intermediate Spinal Instability Neoplastic Score (SINS).

Background: Adequate assessment of spinal instability using the spinal instability neoplastic score (SINS) frequently guides surgical therapy in spinal epidural osseous metastases and subsequently influences neurological outcome. However, how to surgically manage 'impending instability' at SINS 7−12 most appropriately remains uncertain. This study aimed to evaluate the necessity of spinal instrumentation in patients with SINS 7−12 with regards to neurological outcome. Methods: We screened 683 patients with spinal epidural metastases treated at our interdisciplinary spine center. The preoperative SINS was assessed to determine spinal instability and neurological status was defined using the Frankel score. Patients were dichotomized according to being treated by instrumentation surgery and neurological outcomes were compared. Additionally, a subgroup analysis of groups with SINS of 7−9 and 10−12 was performed. Results: Of 331 patients with a SINS of 7−12, 76.1% underwent spinal instrumentation. Neurological outcome did not differ significantly between instrumented and non-instrumented patients (p = 0.612). Spinal instrumentation was performed more frequently in SINS 10−12 than in SINS 7−9 (p < 0.001). The subgroup analysis showed no significant differences in neurological outcome between instrumented and non-instrumented patients in either SINS 7−9 (p = 0.278) or SINS 10−12 (p = 0.577). Complications occurred more frequently in instrumented than in non-instrumented patients (p = 0.016). Conclusions: Our data suggest that a SINS of 7−12 alone might not warrant the increased surgical risks of additional spinal instrumentation.

Ventriculostomy-related intracranial hemorrhage following surgical and endovascular treatment of ruptured aneurysms.

Endovascular therapy of ruptured aneurysms is regularly accompanied by periprocedural heparinization and requires the use of periprocedural antiplatelets in more complex cases. This raises concerns regarding increased bleeding risks in the case of frequently required ventriculostomy. The aim of this study was to analyze risk factors for ventriculostomy-related intracranial hemorrhages (VS-ICH) in endovascular or surgical treatment of ruptured aneurysms with a focus on antithrombotic therapy. In this retrospective analysis, we included patients admitted to our institution over a 12-year period who had received at least one ventriculostomy due to subarachnoid hemorrhage-related hydrocephalus. Patients were dichotomized into an endovascular and surgical group and rates of VS-ICH were compared. Risk factors for VS-ICH were assessed in uni- and multivariate analyses. A total of 606 ventriculostomies were performed in 328 patients. Within the endovascular group, antiplatelet therapy was used in 44.8% of cases. The overall rate of ventriculostomy-related intracranial hemorrhage was 13.1%. Endovascular treatment was associated with a higher rate of VS-ICH compared to surgical treatment (p = 0.011), but not in cases without antiplatelet therapy (p = 0.166). Application of any antiplatelet therapy (odds ratio, 2.647 [95% confidence interval, 1.141-6.143]) and number of ventriculostomies (odds ratio, 2.513 [95% confidence interval, 1.859-3.395]) were independent predictors of ventriculostomy-related hemorrhages. Our findings indicate an increased risk of VS-ICH in the endovascular group if administration of antiplatelets was required. While this aspect has to be included into treatment decision-making, it must be weighed against the benefits of endovascular techniques.

Cyberknife® hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases.

PURPOSE: The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature. METHODS: All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%. The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively. Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1-3 were observed in 12%. CONCLUSION: Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.

Preoperative Three-Dimensional Angiography May Reduce Ischemic Complications During Clipping of Ruptured Intracranial Aneurysms.

OBJECTIVE: Microsurgical clipping of aneurysms demands precise spatial understanding of aneurysm morphology and vascular geometry. We analyzed the impact of preoperative three-dimensional (3D) angiographic imaging on clinical and angiographic outcome after clipping of ruptured intracranial aneurysms. METHODS: This is a retrospective analysis of consecutive patients who underwent microsurgical clipping during the acute phase of subarachnoid hemorrhage between 2010 and 2017. Surgical planning was made based on two-dimensional (2D) or 3D angiographic images. We retrospectively compared complication rates, morbidity, and angiographic outcome between these 2 groups. RESULTS: A total of 157 patients (mean age: 54.8 ± 13.1 years) were included in the study. Preoperative 3D angiographic imaging was available for 117 cases. The rate of procedure-related ischemia was significantly lower in the 3D group (16.2%) than in the 2D group (35.0%; P = 0.013). In the multivariate analysis, 2D imaging alone remained as independent factor for subsequent brain ischemia (odds ratio: 2.8, 95% confidence interval 1.2-6.6; P = 0.018). Favorable outcome (modified Rankin scale ≤2) was more often attained in the 3D group (70.0%) than in the 2D group (41.9%; P = 0.002). The rate of complete aneurysm occlusion was not significantly different between the 2 groups (P = 0.967). CONCLUSIONS: In our study, accurate operation planning using 3D angiography was associated with a lower ischemic complication rate after clipping of ruptured intracranial aneurysms, which may potentially influence clinical outcome.

Impact of Aneurysm Shape on Intraoperative Rupture During Clipping of Ruptured Intracranial Aneurysms.

OBJECTIVE: Irregular shape is a known risk factor of intracranial aneurysm rupture causing subarachnoid hemorrhage. The objective of this study was to determine the impact of aneurysm shape on intraoperative rupture (IOR) during microsurgical clipping of ruptured aneurysms. METHODS: This is a retrospective, single-center study of consecutive patients that underwent clipping between 2010 and 2017. Based on 3-dimensional reconstructions from preoperative computed tomography scan and digital subtraction angiography, aneurysm shape was classified as regular aneurysm (RA) or irregular aneurysm (IRA). Risk factors for IOR were identified using univariate and multivariate statistical analyses. RESULTS: A total of 138 patients with 32 RAs and 102 IRAs were included in the analysis. IRAs had a larger size than RAs (8.3 ± 3.5 vs. 4.6 ± 2.3 mm, respectively; P < 0.001). There were 36 instances of IOR (26.1%). The IOR rate was greater in IRAs than in RAs (31.1% vs. 9.4%, respectively; P = 0.02). In multivariate analysis, IRA shape was the only significant independent risk factor for IOR (odds ratio, 3.9; 95% confidence interval, 1.0-14.6; P = 0.047). Unfavorable outcome (modified Rankin scale score greater than 2) was not significantly associated with aneurysm shape (P = 0.998) and IOR (P = 0.260). CONCLUSIONS: Our results demonstrate that IRA shape is an independent risk factor for IOR. In the analyzed patient cohort, aneurysm shape and IOR had no significant impact on patient prognosis.

Current treatment concepts for iatrogenic ventriculitis: a nationwide survey in Germany.

BACKGROUND: Iatrogenic ventriculitis is a common complication of the external ventricular drainage. While the procedure and indications for external ventricular drains (EVD) are highly standardized, the treatment of ventriculitis is not clearly defined. OBJECTIVE: To depict the treatment of iatrogenic ventriculitis currently performed in German hospitals. METHODS: A standardized questionnaire consisting of 18 multiple choice questions, each with the ability to provide additional individual answers, covering the diagnosis and treatment of iatrogenic ventriculitis as well as general handling of EVDs, was sent to 121 neurosurgical hospitals registered in the German Society for Neurosurgery (DGNC). RESULTS: Thirty-three out of 121 hospitals returned the questionnaire. While diagnostics are performed similarly in most hospitals, the treatment varies remarkably. Ten of the 33 (30%) units never applied antibiotics intrathecally and 12 (36%) only in selected (1-20%) cases, while 7 (21%) do this routinely, and the remaining 4 centers vary their treatment. While the targeted systemic therapy after pathogen identification and resistance testing is similar, the choice of empiric antibiotics varies as does the type of drug used for intrathecal therapy. Among the applied systemic antibiotics, vancomycin [n = 23 (70%)] and meropenem [n = 22 (67%)] were the most common, but many others, including ceftriaxone, metronidazol, linezolid, piperacillin/tazobactam, fosfomycin and ceftazidim, are used. There is no standard practice regarding EVD handling. Twelve (36%) hospitals do not replace the EVD after a new diagnosis of ventriculitis, 13 (39%) do so once after the diagnosis, and 8 (24%) regularly switch EVDs after a defined time span (7-20 days), even without signs of infection. CONCLUSION: Treatment concepts for iatrogenic ventriculitis are very heterogeneous. Thus, there is an urgent need for generating outcome data and defining a standard treatment algorithm with the recently published practice guideline being an important first step.

Cytokinesis failure and successful multipolar mitoses drive aneuploidy in glioblastoma cells.

Glioblastoma (GB) is the most frequent human brain tumor and is associated with a poor prognosis. Multipolar mitosis and spindles have occasionally been observed in cultured glioblastoma cells and in glioblastoma tissues, but their mode of origin and relevance have remained unclear. In the present study, we investigated a novel GB cell line (SGB4) exhibiting mitotic aberrations and established a functional link between cytokinesis failure, centrosome amplification, multipolar mitosis and aneuploidy in glioblastoma. Long-term live cell imaging showed that >3% of mitotic SGB4 cells underwent multipolar mitosis (tripolar>tetrapolar>pentapolar). A significant amount of daugther cells generated by multipolar mitosis were viable and completed several rounds of mitosis. Pedigree analysis of mitotic events revealed that in many cases a bipolar mitosis with failed cytokinesis occurred prior to a multipolar mitosis. Additionally, we observed that SGB4 cells were also able to undergo a bipolar mitosis after failed cytokinesis. Colchicine-induced mitotic arrest and metaphase spreads demonstrated that SGB4 cells had a modal chromosome number of 58 ranging from 23 to 170. Approximately 82% of SGB4 cells were hyperdiploid (47-57 chromosomes) or hypotriploid (58-68 chromosomes). In conclusion, SGB4 cells passed through multipolar cell divisions and generated viable progeny by reductive mitoses. Our results identified cytokinesis failure occurring before and after multipolar or bipolar mitoses as important mechanisms to generate chromosomal heterogeneity in glioblastoma cells.