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%.

Does Early Mobilization Following Resection of Spinal Intra-Dural Pathology Increase the Risk of Cerebrospinal Fluid Leaks?-A Dual-Center Comparative Effectiveness Research.

Background and Objectives: Prolonged bed rest after the resection of spinal intradural tumors is postulated to mitigate the development of cerebrospinal fluid leaks (CSFLs), which is one of the feared postoperative complications. Nonetheless, the empirical evidence supporting this conjecture remains limited and requires further investigation. The goal of the study was to investigate whether prolonged bed rest lowers the risk of CSFL after the resection of spinal intradural tumors. The primary outcome was the rate of CSFL in each cohort. Materials and Methods: To validate this hypothesis, we conducted a comparative effectiveness research (CER) study at two distinct academic neurosurgical centers, wherein diverse postoperative treatment protocols were employed. Specifically, one center adopted a prolonged bed rest regimen lasting for three days, while the other implemented early postoperative mobilization. For statistical analysis, case-control matching was performed. Results: Out of an overall 451 cases, we matched 101 patients from each center. We analyzed clinical records and images from each case. In the bed rest center, two patients developed a CSFL (n = 2, 1.98%) compared to four patients (n = 4, 3.96%) in the early mobilization center (p = 0.683). Accordingly, CSFL development was not associated with early mobilization (OR 2.041, 95% CI 0.365-11.403; p = 0.416). Univariate and multivariate analysis identified expansion duraplasty as an independent risk factor for CSFL (OR 60.33, 95% CI: 0.015-0.447; p < 0.001). Conclusions: In this CER, we demonstrate that early mobilization following the resection of spinal intradural tumors does not confer an increased risk of the development of CSFL.

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.

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.

Impact of Obesity on Complication Rates, Clinical Outcomes, and Quality of Life after Minimally Invasive Transforaminal Lumbar Interbody Fusion.

BACKGROUND: Percutaneous pedicle screw fixation in obese patients remains a surgical challenge. We aimed to compare patient-reported outcomes and complication rates between obese and nonobese patients who were treated by minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: The authors retrospectively reviewed patients who underwent MIS-TLIF at a single institution between 2011 and 2014. Patients were classified as obese (body mass index [BMI] ≥30 kg/m2) or nonobese (BMI < 30 kg/m2), according to their BMI. Outcomes assessed were complications, numerical rating scale (NRS) scores for back and leg pain, Oswestry Disability Index (ODI), and 36-Item Short-Form Survey (SF-36) scores. RESULTS: The final study group consisted of 71 patients, 24 obese (33.8%, 34.8 ± 3.8 kg/m2) and 47 nonobese (66.2%, 25.4 ± 2.9 kg/m2). Instrumentation failures (13.6 vs. 17.0%), dural tears (17.2 vs. 4.0%), and revision rates (16.7 vs. 19.1%) were similar between both groups (p > 0.05). Perioperative improvements in back pain (4.3 vs. 5.4, p = 0.07), leg pain (3.8 vs. 4.2, p = 0.6), and ODI (13.3 vs. 22.5, p = 0.5) were comparable among the groups and persisted at long-term follow-up. Obese patients had worse postoperative physical component SF-36 scores than nonobese patients (36.4 vs. 42.7, p = 0.03), while the mental component scores were not statistically different (p = 0.09). CONCLUSION: Obese patients can achieve similar improvement of the pain intensity and functional status even at long-term follow-up. In patients with appropriate surgical indications, obesity should not be considered a contraindication for MIS-TLIF surgery.

Qualitative and Quantitative Analysis of IDH1 Mutation in Progressive Gliomas by Allele-Specific qPCR and Western Blot Analysis.

To date, diagnosis of IDH1 mutation is based on DNA sequencing and immunohistochemistry, methods limited in terms of sensitivity and ease of use. Recently, the diagnosis of IDH1 mutation by real-time polymerase chain reaction was introduced as an alternative method. In this study, real-time polymerase chain reaction was validated as a tool for detection of IDH1 mutation, and expression levels were analyzed for correlation with course of the disease. A total of 113 tumor samples were obtained intraoperatively from 84 patients with glioma having a diagnosis of diffuse glioma (World Health Organization II), anaplastic glioma (World Health Organization III), secondary glioblastoma ± chemotherapy, primary glioblastoma ± chemotherapy (World Health Organization IV). Tumor samples were snap frozen and processed for sectioning and RNA and protein isolation. Presence of IDH1 mutation was determined by DNA sequencing. Hereafter, quantitative expression of IDH1 messenger RNA was assessed using real-time polymerase chain reaction with specific primers for IDH1 mutation and -wt; protein expression was verified by Western Blot analysis and immunohistochemistry. Additionally, 19 samples of low-grade glioma and their consecutive high-grade glioma were analyzed at different time points of the disease. IDH1 mutation was identified in 63% of samples by DNA sequencing. In correlation with the real-time polymerase chain reaction results, a cutoff value was determined. Above this threshold, sensitivity and specificity of real-time polymerase chain reaction in detecting IDH1 mutation were 98% and 94%, respectively. Quantitative analysis revealed that IDH1 mutation expression is upregulated in secondary glioblastoma (mean ± standard error of mean: 3.52 ± 0.55) compared to lower grade glioma (II = 1.54 ± 0.22; III = 1.67 ± 0.23). In contrast, IDH1 wt expression is upregulated in all glioma grades (concentration >0.1) compared to control brain tissue (0.007 ± 0.0016). Western Blot analysis showed a high concordance to both sequencing and real-time polymerase chain reaction results in qualitative analysis of IDH1 mutation status (specificity 100% and sensitivity 100%). Moreover, semiquantitative protein expression analysis also showed higher expression levels of mutated IDH1 in secondary glioblastoma. In our study, real-time polymerase chain reaction and Western Blot analysis were found to be highly efficient methods in detecting IDH1 mutation in glioma samples. As cost-effective and time-saving methods, real-time polymerase chain reaction and Western Blot analysis may therefore play an important role in IDH1 mutation analysis in the future. IDH1 mutation expression level was found to correlate with the course of disease to a certain extent. Yet, clinical factors as recurrent disease or prior radiochemotherapy did not alter IDH1 mutation expression level.

The Impact of Cage Dimensions, Positioning, and Side of Approach in Extreme Lateral Interbody Fusion.

STUDY DESIGN: This is a retrospective single-center study. OBJECTIVE: The aim of the study was to evaluate the impact of cage characteristics and position toward clinical and radiographic outcome measures in patients undergoing extreme lateral interbody fusion (ELIF). SUMMARY OF BACKGROUND DATA: ELIF is utilized for indirect decompression and minimally invasive surgical treatment for various degenerative spinal disorders. However, evidence regarding the influence of cage characteristics in patient outcome is minimal. MATERIALS AND METHODS: Patients undergoing ELIF between 2007 and 2011 were included in a retrospective study. Demographic and perioperative data, as well as cage characteristics and side of approach were extracted. Radiographic parameters including lumbar lordosis, foraminal height, and disc height as well as clinical outcome parameters (Oswestry Disability Index and Visual Analog Scale) were measured preoperatively, postoperatively, and at the latest follow-up examination. Cage dimensions, in situ position, and type were correlated with radiographic and clinical outcome parameters. RESULTS: In total, 84 patients with a total of 145 functional spinal units were analyzed. At the last follow-up of 17.7 months, radiographic and clinical outcome measures revealed significant improvement compared with before surgery with both, 18 and 22 mm cage anterior-posterior diameter subgroups (P≤0.05). Among cage characteristics, 22 mm cages presented superior restoration of foraminal and disc heights compared with 18 mm cages (P≤0.05). Neither position of the cage (anterior vs. posterior), nor the type (parallel vs. lordotic) had a significant impact on restoration of foraminal height and lumbar lordosis. Moreover, the side of surgical approach did not influence the amount of foraminal height increase. CONCLUSIONS: Cage anterior-posterior diameter is the determining factor in restoration of foraminal height in ELIF. Cage height, type, positioning, and side of approach do not have a determining role in radiographic outcome in the present study. Sustainable foraminal height restoration is achieved by implantation of wider cages. LEVEL OF EVIDENCE: Level 3.

Repair of Cerebrospinal Fluid Leakage Using a Transfrontal, Radial Adipofascial Flap: An Individual Approach Supported by Three-Dimensional Printing for Surgical Planning.

BACKGROUND: Leakage of cerebrospinal fluid (CSF) because of large prolactinomas represents a complex issue. Because of limited anatomic space, multiple leakage sites, and scarce locally available tissue for repair, surgical possibilities are limited. We report an initial case of using a radial fasciocutaneous flap applied subfrontally to cover a large skull base defect, supported by preoperative three-dimensional (3D) printing for surgical planning. CASE DESCRIPTION: A 29-year-old woman developed severe nuchal pain that was caused by destruction of large parts of her skull base by a prolactinoma. After occipitocervical fusion, medical treatment showed good tumor response but led to CSF leakage after 12 months. An endoscopic approach and ventriculoperitoneal shunt implantation failed to stop the leakage. A 3D model of the skull improved the understanding of the expanded osseous destruction and multiple CSF leakage sites and supported surgical planning. For an extensive coverage of the former clivus and sella region, an intracranially applied radial flap was planned. Dopamine-agonist medication was increased before the operation. Intraoperatively, the flap was brought into position subchiasmatically and wound around the pituitary stalk. CSF leakage was not observed on follow-up (10 weeks). Long-term follow-up will determine the effectiveness of this method.

Potential and Limitations of Neural Decompression in Extreme Lateral Interbody Fusion-A Systematic Review.

BACKGROUND: Extreme lateral interbody fusion (ELIF) is a powerful tool for interbody fusion and coronal deformity correction. However, evidence regarding the success of ELIF in decompressing foraminal, lateral recess, and central canal stenosis is lacking. We performed a systematic review of current literature on the potential and limitations of ELIF to indirectly decompress neural elements. METHODS: A literature search using PubMed, Cochrane, and ScienceDirect databases was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Information on study design, sample size, population, procedure, number and location of involved levels, follow-up time, and complications as well as information on conflict of interest was extracted and evaluated. RESULTS: We selected 20 publications including 1080 patients for review. Most publications (90%) were retrospective case series. Most frequent indications for ELIF included degenerative disc disease, spinal stenosis, spondylolisthesis, and degenerative scoliosis. Most studies revealed significant improvement in radiographic and clinical outcome after ELIF. Mean foraminal area, central canal area, and subarticular diameter increased by 31.6 mm2, 28.5 mm2, and 0.85 mm. ELIF successfully improved foraminal stenosis. Contradictory results were found for indirect decompression of central canal stenosis. Data on lateral recess stenosis were scarce. CONCLUSIONS: Current data suggest ELIF to be an efficient technique in decompression of foraminal stenosis. Evidence on decompression of central canal or lateral recess stenosis via ELIF is low, and results are inconsistent. Most studies are limited by study design, sample size, and potential conflicts of interest.

Long-term Functional Recovery and Quality of Life after Surgical Treatment of Putaminal Hemorrhages.

BACKGROUND: To evaluate the long-term functional recovery and health-related quality of life (HRQOL) in patients after surgically treated putaminal hemorrhages. Surgery for putaminal hemorrhages remains a controversial issue. Although numerous reports describe conflictive results regarding short-term outcome of surgically treated patients, very little is known about their long-term recovery and their HRQOL. METHODS: In this monocentric, retrospective study we analyzed mortality, long-term functional outcome, activity of daily life status, and HRQOL undergoing craniotomy for hematoma evacuation between December 2004 and January 2011. RESULTS: Forty-nine consecutive patients were identified with 8 (16.3%) patients dying during acute care. Forty-one patients surviving acute phase were transferred to neurologic rehabilitation hospitals. One patient was lost to follow-up. Median follow-up was 52.9 (17-101) months. At follow-up, 24 of 40 (60%) patients still were alive with 16 of 40 (40%) patients living with major disability (modified Rankin Scale [mRS], 4 or 5). Seven patients (17.5%) showed a mRS lesser than or equal to 3 with only 3 (7.5%) of those living functionally independent (mRS, 0-2). HRQOL in survivors was reduced with a median DEMQOL/DEMQOL (a patient/caregiver reported outcome measure designed to assess health-related quality of life of people with dementia) proxy score of 92 and 93, respectively. All patients showed severe impairment in activities of daily life. CONCLUSIONS: This is the first long-term follow-up analysis for patients with surgically treated putaminal hemorrhages. Survivors show only marginal recovery despite intensive neurologic rehabilitation; most remain dependent with a reduced HRQOL and significantly impaired activities of daily life status.

Functional energetics of CD4+-cellular immunity in monoclonal antibody-associated progressive multifocal leukoencephalopathy in autoimmune disorders.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system- (CNS-) infection that typically occurs in a subset of immunocompromised individuals. An increasing incidence of PML has recently been reported in patients receiving monoclonal antibody (mAb) therapy for the treatment of autoimmune diseases, particularly those treated with natalizumab, efalizumab and rituximab. Intracellular CD4(+)-ATP-concentration (iATP) functionally reflects cellular immunocompetence and inversely correlates with risk of infections during immunosuppressive therapy. We investigated whether iATP may assist in individualized risk stratification for opportunistic infections during mAb-treatment. METHODOLOGY/PRINCIPAL FINDINGS: iATP in PHA-stimulated, immunoselected CD4(+)-cells was analyzed using an FDA-approved assay. iATP of mAb-associated PML (natalizumab (n = 8), rituximab (n = 2), efalizumab (n = 1)), or other cases of opportunistic CNS-infections (HIV-associated PML (n = 2), spontaneous PML, PML in a psoriasis patient under fumaric acids, natalizumab-associated herpes simplex encephalitis (n = 1 each)) was reduced by 59% (194.5±29 ng/ml, mean±SEM) in comparison to healthy controls (HC, 479.9±19.8 ng/ml, p<0.0001). iATP in 14 of these 16 patients was at or below 3(rd) percentile of healthy controls, similar to HIV-patients (n = 18). In contrast, CD4(+)-cell numbers were reduced in only 7 of 15 patients, for whom cell counts were available. iATP correlated with mitochondrial transmembrane potential (ΔΨ(m)) (iATP/ΔΨ(m)-correlation:tau = 0.49, p = 0.03). Whereas mean iATP of cross-sectionally analysed natalizumab-treated patients was unaltered (448.7±12 ng/ml, n = 150), iATP was moderately decreased (316.2±26.1 ng/ml, p = 0.04) in patients (n = 7) who had been treated already during the pivotal phase III trials and had received natalizumab for more than 6 years. 2/92 (2%) patients with less than 24 months natalizumab treatment revealed very low iATP at or below the 3(rd) percentile of HC, whereas 10/58 (17%) of the patients treated for more than 24 months had such low iATP-concentrations. CONCLUSION: Our results suggest that bioenergetic parameters such as iATP may assist in risk stratification under mAb-immunotherapy of autoimmune disorders.

Mitochondrial haplogroup H correlates with ATP levels and age at onset in Huntington disease.

Mitochondrial dysfunction has been implicated in the pathogenesis of Huntington disease (HD), a primarily neurodegenerative disorder that results from an expansion in the polymorphic trinucleotide CAG tract in the HD gene. In order to evaluate whether mitochondrial DNA (mtDNA) variation contributes to HD phenotype we genotyped 13 single nucleotide polymorphisms (SNPs) that define the major European mtDNA haplogroups in 404 HD patients. Genotype-dependent functional effects on intracellular ATP concentrations were assessed in peripheral leukocytes. In patients carrying the most common haplogroup H (48.3%), we demonstrate a significantly lower age at onset (AO). In combination with PGC-1 alpha genotypes, 3.8% additional residual variance in HD AO can be explained. Intracellular ATP concentrations in HD patients carrying the cytochrome c oxidase subunit I (CO1) 7028C allele defining haplogroup H were significantly higher in comparison to non-H individuals (mean +/- SEM, 599 +/- 51.8 ng/ml, n = 14 vs. 457.5 +/- 40.4 ng/ml, p = 0.03, n = 9). In contrast, ATP concentrations in cells of HD patients independent from mtDNA haplogroup showed no significant differences in comparison to matched healthy controls. Our data suggest that an evolutionarily advantageous mitochondrial haplogroup is associated with functional mitochondrial alterations and may modify disease phenotype in the context of neurodegenerative conditions such as HD.