Large symptomatic sacral Tarlov cyst in a paediatric patient: case report and technical note on a new variation of surgical technique to overcome one-way check-valve mechanism.

PURPOSE: Symptomatic Tarlov cysts in children with a possible underlying one-way check-valve mechanism are very rare. We aim to introduce a new variation of the surgical technique to overcome a check-valve mechanism. METHODS: A 15-years-old girl presented with double incontinence and anogenital numbness due to a large sacral Tarlov-cyst with possibly underlying one-way check valve mechanisms as suggested by preoperative computed tomography myelography. Intraoperatively, one-way check-valve was confirmed and could be eliminated by creating an artificial inner ostium between the Tarlov cyst and thecal sac with blunt perforation. RESULTS: Postoperatively, the patient had established normal sphincter control and sensation in the anogenital region. CONCLUSION: One-way check-valve mechanism might contribute to the symptomatology of large sacral Tarlov cysts in children. Our new variation of a surgical technique enables elimination of the check-valve mechanism without the necessity to open and close the typically very thin and fragile cyst surface and is therefore an efficacious and simple option in this situation.

Reducing the rate of surgical site infection using iodophor-impregnated adhesive incision draping in spine surgery compared with standard adhesive incision draping: a study in 2279 patients.

OBJECTIVE: While adhesive incision drapes are widely used for reducing surgical site infection (SSI), evidence remains scarce on whether impregnated adhesive incision draping can further reduce the rate of SSI in spine surgery. METHODS: All patients treated surgically in the authors' high-volume university spine center from January 2018 to December 2021 were retrospectively evaluated and divided into cohorts treated before (the control cohort) and after (the study cohort) introduction of an iodophor-impregnated adhesive incision drape (instead of a standard nonimpregnated adhesive incision drape) at their institute. Epidemiological aspects, baseline characteristics, operative records, and rate and characteristics of postoperative SSI were analyzed and compared between cohorts. RESULTS: Two thousand two hundred seventy-nine consecutively treated patients were included, with an overall SSI rate of 0.5%. Baseline patient findings and surgical characteristics (including indication, localization, procedure, and duration of surgery) did not significantly differ between the 1125 patients in the control cohort and the 1154 patients in the study cohort. Uni- and multivariate analyses showed that use of an iodophor-impregnated adhesive incision drape was the only factor significantly associated with a lower risk of SSI. The SSI rate was significantly lower in the study cohort (0.2% vs 0.8%, p = 0.036). While germs of the skin microbiome such as Staphylococcus epidermidis and S. aureus were predominantly prevalent in both cohorts, fecal germs such as Enterococcus/Enterobacter species were found only in the control cohort and not in the study cohort. CONCLUSIONS: The use of iodophor-impregnated adhesive incision drapes in spine surgery can help to lower the rate of postoperative SSI and aid in reducing the risk of fecal germ infections.

Outcome of posterior decompression for spinal epidural lipomatosis.

BACKGROUND: In contrast to osteoligamentous lumbar stenosis (LSS), outcome of surgical treatment for spinal epidural lipomatosis (SEL) is still not well defined. We present risk factors for SEL and clinical long-term outcome data after surgical treatment for patients with pure SEL and a mixed-type pathology with combined SEL and LSS (SEL+LSS) compared to patients with pure LSS. METHODS: From our prospective institutional database, we identified all consecutive patients who were surgically treated for newly diagnosed SEL (n = 31) and SEL+LSS (n = 26) between 2018 and 2022. In addition, a matched control group of patients with pure LSS (n = 30) was compared. Microsurgical treatment aimed for posterior decompression of the spinal canal. Study endpoints were outcome data including clinical symptoms at presentation, MR-morphological analysis, evaluation of pain-free walking distance, pain perception by VAS-N/-R scales, and patient's satisfaction by determination of the Odom score. RESULTS: Patients with osteoligamentous SEL were significantly more likely to suffer from obesity (body mass index (BMI) of 30.2 ± 5.5 kg/m2, p = 0.03), lumbar pain (p = 0.006), and to have received long-term steroid therapy (p = 0.01) compared to patients with SEL+LSS and LSS. In all three groups, posterior decompression of the spinal canal resulted in significant improvement of these symptoms. Patients with SEL had a significant increase in pain-free walking distance during the postoperative course, at discharge, and last follow-up (FU) (p < 0.0001), similar to patients with SEL+LSS and pure LSS. In addition, patients with pure SEL and SEL+LSS had a significant reduction in pain perception, represented by smaller values of VAS-N and -R postoperatively and at FU, similar to patients with pure LSS. In uni- and multivariate analysis, domination of lumbar pain and steroid long-term therapy were significant characteristic risk factors for SEL. CONCLUSIONS: Surgical treatment of pure SEL and SEL+LSS allows significant improvement in pain-free walking distance and pain perception immediately postoperatively and in long-term FU, similar to patients with pure LSS.

Differentiation of benign and malignant vertebral fractures using a convolutional neural network to extract CT-based texture features.

PURPOSE: To assess the diagnostic performance of three-dimensional (3D) CT-based texture features (TFs) using a convolutional neural network (CNN)-based framework to differentiate benign (osteoporotic) and malignant vertebral fractures (VFs). METHODS: A total of 409 patients who underwent routine thoracolumbar spine CT at two institutions were included. VFs were categorized as benign or malignant using either biopsy or imaging follow-up of at least three months as standard of reference. Automated detection, labelling, and segmentation of the vertebrae were performed using a CNN-based framework ( https://anduin.bonescreen.de ). Eight TFs were extracted: Varianceglobal, Skewnessglobal, energy, entropy, short-run emphasis (SRE), long-run emphasis (LRE), run-length non-uniformity (RLN), and run percentage (RP). Multivariate regression models adjusted for age and sex were used to compare TFs between benign and malignant VFs. RESULTS: Skewnessglobal showed a significant difference between the two groups when analyzing fractured vertebrae from T1 to L6 (benign fracture group: 0.70 [0.64-0.76]; malignant fracture group: 0.59 [0.56-0.63]; and p = 0.017), suggesting a higher skewness in benign VFs compared to malignant VFs. CONCLUSION: Three-dimensional CT-based global TF skewness assessed using a CNN-based framework showed significant difference between benign and malignant thoracolumbar VFs and may therefore contribute to the clinical diagnostic work-up of patients with VFs.

The impact of initial counselling for patients' decision-making and the accuracy of interdisciplinary neurovascular board evaluation in elective treatment of unruptured intracranial aneurysms - a German single-centre retrospective study.

OBJECTIVE: Interdisciplinary-neurovascular-boards (INVB) are deemed to find the patient's optimum treatment-modality in elective unruptured intracranial aneurysm-repair (EUIAR). If INVB judges risk/success estimation similar for microsurgical/endovascular EUIAR, the choice for either modality is up to the informed patient. However, it is unknown if the patients' decision-making might be biased by the discipline of initial counselling prior to INVB and if INVB's equal risk/success estimation is finally accurate. METHODS: We analysed all our patients with EUIAR after INVB-discussion between 2007 and 2017 and identified those patients where INVB-recommendation estimated similar risk/success rates for both treatment-modalities. We investigated the procedural/outcome parameters and determined if the mode of initial counselling prior to INVB influenced the patients' choice of EUIAR and if INVB's equal risk/success estimation was accurate. RESULTS: Within altogether 572 patients with EUIAR during our study period, we identified 99 patients (agemean:58 yrs; m:f=1:2) in whom pre-treatment INVB-discussion estimated risk/success rates for both modalities of EUIAR to be similar. Prior to INVB-discussion, 80 of the 99 patients had been initially counselled in the neurosurgical discipline and 19 patients in the endovascular discipline. The final patients' decision rates for surgical vs. endovascular EUIAR (after secondary consultation of each patient in both disciplines after INVB-discussion) were 67% vs. 33% in the first and 58% vs. 42% in the latter group (no significant difference: p = 0.345). Uni- and multivariate analysis did not show any hints for a bias in patients' decision-making caused by the discipline of initial counselling prior to INVB/secondary bilateral consultations. Clinical and procedural outcome at last follow-up (median:18mos) did not differ between those 66 patients that eventually decided for microsurgical and those 33 patients that eventually decided for endovascular EUIAR, underlining the high accuracy of INVB's pre-treatment risk/success estimations. CONCLUSION: Only in a small number of patients, INVB estimates both disciplines to be of equal value for EUIAR which proves to be highly accurate at long-term outcome measures. Initial contact to one or the other neurovascular discipline does not appear to play a significant role in the final patient's decision-making process.

Automated Opportunistic Trabecular Volumetric Bone Mineral Density Extraction Outperforms Manual Measurements for the Prediction of Vertebral Fractures in Routine CT.

Opportunistic osteoporosis screening using multidetector CT-scans (MDCT) and convolutional neural network (CNN)-derived segmentations of the spine to generate volumetric bone mineral density (vBMD) bears the potential to improve incidental osteoporotic vertebral fracture (VF) prediction. However, the performance compared to the established manual opportunistic vBMD measures remains unclear. Hence, we investigated patients with a routine MDCT of the spine who had developed a new osteoporotic incidental VF and frequency matched to patients without incidental VFs as assessed on follow-up MDCT images after 1.5 years. Automated vBMD was generated using CNN-generated segmentation masks and asynchronous calibration. Additionally, manual vBMD was sampled by two radiologists. Automated vBMD measurements in patients with incidental VFs at 1.5-years follow-up (n = 53) were significantly lower compared to patients without incidental VFs (n = 104) (83.6 ± 29.4 mg/cm3 vs. 102.1 ± 27.7 mg/cm3, p < 0.001). This comparison was not significant for manually assessed vBMD (99.2 ± 37.6 mg/cm3 vs. 107.9 ± 33.9 mg/cm3, p = 0.30). When adjusting for age and sex, both automated and manual vBMD measurements were significantly associated with incidental VFs at 1.5-year follow-up, however, the associations were stronger for automated measurements (ß = -0.32; 95% confidence interval (CI): -20.10, 4.35; p < 0.001) compared to manual measurements (ß = -0.15; 95% CI: -11.16, 5.16; p < 0.03). In conclusion, automated opportunistic measurements are feasible and can be useful for bone mineral density assessment in clinical routine.

Feasibility of multimodal intraoperative neurophysiological monitoring for extramedullary spinal cord tumor surgery in elderly patients.

BACKGROUND/PURPOSE: Extramedullary spinal cord tumors (EMSCTs) are mostly benign tumors which are increasingly diagnosed and operatively treated in the elderly. While there are hints that multimodal intraoperative neurophysiological monitoring (IONM) could be influenced by age and age-related comorbidities, no study has ever systematically evaluated its feasibility and value for EMSCT surgery in elderly patients. METHODS: We retrospectively evaluated all patients with microsurgical EMSCT resection under continuous multimodal IONM with SSEPs, MEPs and electromyography between 2016 and 2020. Epidemiological, clinical, imaging and operative/IONM records as well as detailed individual outcomes were analyzed and compared for the cohort < / ≥ 65 years. RESULTS: Mean age was 45 years in cohort < 65 years (n = 109) and 76 years in cohort ≥ 65 years (n = 64), while baseline/operative characteristics did not significantly differ. Mean baseline SSEPs' latencies (left-right average) were significantly higher in the cohort ≥ 65 years for both median (20.9 ms vs. 22.1 ms; p < 0.01) and tibial nerve (42.9 ms vs. 46.1 ms; p < 0.01) without significant differences for SSEPs' amplitudes. Stimulation intensity to elicit intraoperative MEPs was significantly higher in the cohort ≥ 65 years (surrogate-marker: left-right-averaged quotient ID1-muscle/abductor-hallucis-muscle; 1.6 vs. 2.1; p < 0.001). Intraoperatively, SSEP and MEP monitoring were feasible in 99%/100% and 99%/98% for the cohort < / ≥ 65 years without significant differences in rates for significant IONM changes during surgery or postoperatively new sensorimotor deficits. Sensitivity of IONM was 29%/43%, specificity 99%/98%, positive and negative predictive values 67%/75% and 95%/93% for the cohort < / ≥ 65 years. Overall, age was no risk factor for IONM feasibility or rate of significant IONM changes. DISCUSSION: Multimodal IONM is feasible/reliable for EMSCT surgery in elderly patients. An age-related prolongation of SSEPs' latencies and demand for higher stimulation intensities for MEPs' elicitation has to be considered.

Dorsal column mapping in resection of intramedullary spinal cord tumors: a prospective comparison of two methods and neurological follow-up.

PURPOSE: In surgery for intramedullary spinal cord tumors (imSCT), distortion of the anatomy challenges the visual identification of dorsal columns (DC) for midline myelotomy. Dorsal column mapping (DCM) and spinal cord stimulation (SCS) can identify DC neurophysiologically. We compare application and feasibility of both methods. METHODS: Patients with surgically treated imSCT were prospectively included between 04/2017 and 06/2019. The anatomical midline (AM) was marked. SSEPs at the DC after stimulation of tibial/median nerve with an 8-channel DCM electrode and cortical SSEP phase reversal at C3/C4 after SCS using a bipolar concentric probe were recorded. Procedural and technical aspects were compared. Standardized neurological examinations were performed preoperatively, 1 week postoperatively and after more than 12 months. RESULTS: The DCM electrode detected the midline in 9/13 patients with handling limitations in the remaining patients. SCS was applicable in all patients with determination of the midline in 9/13. If both recordings could be acquired (6/13), concordance was 100%. If baseline SSEPs were poor, both methods were limited. SCS was less time-consuming (p = 0.001), cheaper, and easier to handle. In 92% of cases, the AM and neurophysiologic midlines were concordant. After myelotomy, 3 patients experienced > 50% reduction in amplitude of SSEPs. Despite early postoperative worsening of DC function, long-term follow-up showed significant recovery and improvement in quality of life. CONCLUSION: DCM and SCS may help confirm and correct the AM for myelotomy in imSCT, leading to a favorable long-term neurological outcome in this cohort. SCS evolved to be superior concerning applicability, cost-effectiveness, and time expenditure.

Unilateral Approaches for Posterior Spinal Canal Decompression in Cervical Spondylotic Myelopathy-An Evaluation of Conceptual Feasibility.

BACKGROUND: Patients with cervical spondylotic myelopathy (CSM) can be treated with posterior approaches for spinal canal decompression. OBJECTIVE: We compared the patients' outcome after 2 different unilateral and a bilateral posterior approach for decompression to elucidate feasibility and potential procedure-related differences. METHODS: Medical records of 98 patients with CSM undergoing posterior decompression between 2012 and 2018 were assessed. Patients were divided into 3 groups: (1) unilateral interlaminar fenestration with over-the-top "undercutting" (laminotomy) for compression limited to a ligamentum flavum hypertrophy, (2) unilateral hemilaminectomy for lateralized compression with a combination of ligamentous hypertrophy and osseus stenosis, and (3) laminectomy/laminoplasty for circular osseous-ligamentous spinal canal narrowing. RESULTS: The mean age was 73 years (m:f = 1.4:1), and most frequent symptoms (mean duration: 15 months) were ataxia (69%) and sensory changes (57%). Main location of stenoses (median Naganawa Score = 3; mean anteroposterior spinal canal diameter = 7.7 ± 2.2 mm) was C3 to C6. Thirty-one percent of the patients were assigned for a laminotomy procedure, 20% for a hemilaminectomy, and 49% for a laminectomy/laminoplasty. There were no significant differences of patients' characteristics, blood loss, and operation time between the 3 groups. Independent from the mode of surgery, the spinal canal was significantly widened (median Naganawa Score = 0; mean anteroposterior diameter = 11.4 ± 3.6 mm) and myelopathy (mJOA Score) improved ( P < .001); a higher body mass index was significantly correlated with a worse mJOA improvement (r = 0.293/ P = .003). Quality of life (Short-Form 36v2 Health Survey/Neck Disability Index) and reduction of the neck pain level were similar in the 3 groups at last follow-up (mean: 28 months). CONCLUSION: To minimize patients' periprocedural burden in CSM with dorsal compression, individual tailoring of the posterior approach according to the underlying compressive pathology achieves sufficient decompression and comparable long-term results.

Intramedullary spinal cord cavernous malformations-association between intraoperative neurophysiological monitoring changes and neurological outcome.

BACKGROUND: Microsurgical resection of spinal cord cavernous malformations can be assisted by intraoperative neurophysiological monitoring (IONM). While the clinical outcome after surgical resection has been discussed in several case series, the association of intraoperative IONM changes and detailed neurological outcome, however, has not been analyzed so far. METHODS: Seventeen patients with spinal cavernomas underwent surgery between 02/2004 and 06/2020. Detailed neurological and clinical outcome as well as IONM data including motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring were retrospectively analyzed. Intraoperative IONM changes were compared to outcome at 3-month and 1-year follow-up in order to identify surrogate parameters for an impending neurological deficit. RESULTS: Compared to the preoperative state, McCormick score at 1-year follow-up remained unchanged in 12 and improved in five patients, none worsened, while detailed neurological examination revealed a new or worsened sensorimotor deficit in 4 patients. The permanent 80% amplitude reduction of MEP and 50% amplitude reduction of SSEP showed the best diagnostic accuracy with a sensitivity of 100% and 67% respectively and a specificity of 73% and 93% respectively. The relative risk for a new neurological deficit at 1-year follow-up, when reversible IONM-deterioration was registered compared to irreversible IONM deterioration, was 0.56 (0.23-1.37) for MEP deterioration and 0.4 (0.18-0.89) for SSEP deterioration. CONCLUSIONS: Reversible IONM changes were associated with a better neurological outcome at follow-up compared to irreversible IONM deterioration during SCCM surgery. Our study favors the permanent 80% amplitude reduction criterion for MEP and 50% amplitude reduction criterion for SSEP for further prospective evaluation of IONM significance and the effectiveness of corrective maneuvers during SCCM surgeries.

Intraoperative ultrasonography in laminectomy for degenerative cervical spondylotic myelopathy: a clinical and radiological evaluation.

BACKGROUND: The incidence of cervical myelopathy due to spinal stenosis is constantly growing in an aging population. Especially in multisegmental disease, dorsal laminectomy is the intervention of choice. Intraoperative imaging with ultrasound might provide additional information about extent and sufficiency of spinal cord decompression. METHODS: In this prospective study, the width of the subarachnoid space was systematically measured by intraoperative ultrasound at predefined sites at the cranial and caudal edge of decompression in axial and sagittal reconstruction. These data were compared with corresponding sites on postoperative T2-weighted MRI imaging. In addition, the functional outcome was assessed by modified Japanese Orthopaedic Association (mJOA) score. A historical patient cohort treated without ultrasound-guided laminectomy served as control group. RESULTS: Altogether, 29 patients were included. According to mJOA score at last follow-up, 7/29 patients reported stable symptoms and 21/29 patients showed a substantial benefit with no or minor residual neurological deficits. One patient suffered from a new C5 palsy. Intraoperative ultrasound-guided posterior decompression provided excellent overview in all cases. Measurement of the width of the subarachnoid space acquired by intraoperative ultrasound and postoperative MRI images showed a very high correlation, especially at the cranial level (p < 0.001, r = 0.880). Bland-Altman analysis showed that most patients were within the 1.96 × SD limits of agreement throughout all measurements. No ultrasound procedure-related complications were observed. Compared to a historical cohort of 27 patients, no significant differences were found regarding functional outcome (p = 0.711). CONCLUSION: Intraoperative sonography visualises the surgically achieved restoration of the subarachnoid space in good correlation with postoperative MRI and might serve as a fast, precise and reliable tool for intraoperative imaging in cervical laminectomy. However, we could not demonstrate a clinical benefit with regard to functional outcome.

Routine intraoperative microbiological smear testing in patients with reoperation after elective degenerative non-instrumented spine surgery-useful or negligible adjunct.

PURPOSE: Surgical site infections (SSI) are a rare but dreaded cause for recurrent symptomatology requiring reoperation after degenerative spine surgery. We here aim to elucidate if routine microbiological smear testing during reoperation might be a useful tool for subsequent patient management. METHODS: We investigated clinical, laboratory/imaging characteristics, and outcome of patients undergoing reoperation in the previously affected segment during follow-up after elective degenerative non-instrumented spine surgery. Microbiological cultures via multiple intraoperative smear tests of the superficial/deep wound layers were routinely performed and correlated with clinical/imaging/laboratory/surgical signs for SSI and outcome. RESULTS: From altogether 2552 patients with degenerative spine surgery in 2014-2019, a total of 62 patients (m:f = 1.6:1, median 69 years) underwent same-level reoperation due to recurrent symptomatology (mean ∆-time:17 ± 36 months) with a predominance of the lumbar spine (90%). In 9 patients with imaging/laboratory suspicious for SSI, microbiological culturing of intraoperative smear testing revealed conclusive pathogen growth in 89% (100% with additional PCR analysis); the predominant pathogen was Staphylococcus aureus with detection mainly in the deep wound layers. In contrast, in 53 patients without clinical/imaging/laboratory/intraoperative signs for SSI microbiological culturing showed minor pathogen growth in 15% displaying bacterial colonization/contamination of the surgical site. The predominant pathogens in this cohort were Staphylococcus epidermidis and Cutibacterium acnes, and these patients had favorable outcomes when monitored with close surveillance without anti-infective treatment. CONCLUSION: Bacterial colonization/contamination occurs in 15% of patients without signs of infection undergoing same-level reoperation after degenerative spine surgery. These patients can be managed with close surveillance without antibiotic treatment.

Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

INTRODUCTION: The cIMPACT-NOW update 6 first introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. METHODS: We searched the institutional database for patients with: (1) glioblastoma defined by histopathology; and (2) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. RESULTS: We identified 224 patients with glioblastoma diagnosed based on histopathology, and 54 patients with IDHwt astrocytoma with pTERTmut (19 astrocytomas WHO grade II and 38 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two cohorts as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two cohorts when treated with radio- or chemotherapy. In both cohorts, higher numbers of methylated CpG sites were associated with favourable outcome. CONCLUSIONS: Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both tumor entities, higher numbers of methylated CpG sites appear associated with more favourable outcome. Evaluation in larger prospective cohorts is warranted.

Detection of impending perfusion deficits by intraoperative computed tomography (iCT) in aneurysm surgery of the anterior circulation.

BACKGROUND: The aim of our study was to evaluate the additional benefit of intraoperative computed tomography (iCT), intraoperative computed tomography angiography (iCTA), and intraoperative computed tomography perfusion (iCTP) in the intraoperative detection of impending ischemia to established methods (indocyanine green videoangiography (ICGVA), microDoppler, intraoperative neuromonitoring (IONM)) for initiating timely therapeutic measures. METHODS: Patients with primary aneurysms of the anterior circulation between October 2016 and December 2019 were included. Data of iCT modalities compared to other techniques (ICGVA, microDoppler, IONM) was recorded with emphasis on resulting operative conclusions leading to inspection of clip position, repositioning, or immediate initiation of conservative treatment strategies. Additional variables analyzed included patient demographics, aneurysm-specific characteristics, and clinical outcome. RESULTS: Of 194 consecutive patients, 93 patients with 100 aneurysms received iCT imaging. While IONM and ICGVA were normal, an altered vessel patency in iCTA was detected in 5 (5.4%) and a mismatch in iCTP in 7 patients (7.5%). Repositioning was considered appropriate in 2 patients (2.2%), where immediate improvement in iCTP could be documented. In a further 5 cases (5.4%), intensified conservative therapy was immediately initiated treating the reduced CBP as clip repositioning was not considered causal. In terms of clinical outcome at last FU, mRS0 was achieved in 85 (91.4%) and mRS1-2 in 7 (7.5%) and remained mRS4 in one patient with SAH (1.1%). CONCLUSIONS: Especially iCTP can reveal signs of impending ischemia in selected cases and enable the surgeon to promptly initiate therapeutic measures such as clip repositioning or intraoperative onset of maximum conservative treatment, while established tools might fail to detect those intraoperative pathologic changes.

Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences.

Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection. A 3D treatment-planning software was used to determine the number and suitable positions of the cylindrical diffusing fibers placed stereotactically to ensure optimal interstitial irradiation of the target volume. Outcome measurements included the risk profile of the procedure, estimated time-to-treatment-failure (TTF), post-recurrence survival (PRS) and prognostic factors. Forty-seven patients were treated, of which 44 (median age, 49.4 years, range, 33.4-87.0 years, 27 males) could be retrospectively evaluated. Recurrent gliomas included 37 glioblastomas (WHO grade IV) and 7 anaplastic astrocytomas (WHO grade III). Thirty (68.2%) tumors were O-6-methylguanine-DNA methyltransferase (MGMT)-methylated, 29 (65.9%)-isocitrate dehydrogenase (IDH)-wildtype. Twenty-six (59.1%) patients were treated for their first, 9 (20.5%)-for their second, 9 (20.5%)-for the third or further recurrence. The median iPDT target volume was 3.34 cm3 (range, 0.50-22.8 cm3). Severe neurologic deterioration lasted for more than six weeks in one patient only. The median TTF was 7.1 (95% confidence interval (CI), 4.4-9.8) months and the median PRS was 13.0 (95% CI, 9.2-16.8) months. The 2- and 5-year PRS rates were 25.0% and 4.5%, respectively. The treatment response was heterogeneous and not significantly associated with patient characteristics, treatment-related factors or molecular markers. The promising outcome and acceptable risk profile deserve further prospective evaluation particularly to identify mechanisms and prognostic factors of favorable treatment response.

The number of methylated CpG sites within the MGMT promoter region linearly correlates with outcome in glioblastoma receiving alkylating agents.

MGMT-promoter methylation is associated with favorable outcome in glioblastoma. The aim of this study was to determine whether the absolute number of methylated Cytosine-Guanine-dinucleotide-(CpG-)sites within the DMR-2 island of the MGMT-promoter may correlate with outcome in a qualitative or quantitative fashion. In a cohort of newly diagnosed glioblastoma patients treated with stereotactic biopsy or open tumor resection plus concomitant chemoradiotherapy, we assessed MGMT-promoter methylation by methylation-specific polymerase-chain-reaction (MSP). Methylation of the CpG-sites 74-98 within the MGMT-promoter region was additionally analysed by Sanger sequencing, and the total number of methylated CpG-sites was correlated with outcome using proportional hazards models. 215 patients with glioblastoma were identified and stratified per MSP (positive: 53%, negative: 47%). Among MSP-positive tumors, hierarchical clustering identified three subgroups with different methylation rates (median: 80% vs. 52% vs. 47%), indicating a site-dependent methylation propagation. The methylation status of a given CpG-site indicated a neighborhood-dependent methylation propagation. Survival was linearly associated with the cumulative number of methylated CpG-sites. This was particularly true in patients who received at least one adjuvant cycle of temozolomide. Notably, all CpG-sites analyzed contributed similarly to effect size; this enabled a further predictive substratification of MSP-positive tumors with median OS ranging from as low as 17.1 months (< 18 methylated CpG-sites) to as high as 26.2 months (≥ 18 methylated CpG-sites) in the overall cohort. All in all, total number of methylated CpG-sites may correlate with outcome in a linear fashion. Such analysis may therefore add further predictive value to conventional methods of determining the MGMT-promoter status.

TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression.

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression.

Interleukin-6 as inflammatory marker of surgical site infection following spinal surgery.

BACKGROUND: In order to elucidate whether serum inflammatory markers identify patients with local surgical site infection(SSI) as underlying disease for recurrent or new symptomatology following spine surgery, we evaluated the diagnostic potential of interleukin-6(IL-6) as a marker of SSI. The diagnostic significance of IL-6 was compared to the standard serum inflammatory markers C-reactive protein(CRP) and white blood cell count (WBCC). METHOD: Ninety-eight consecutive patients with readmission due to recurrent or new symptomology after spinal surgery of degenerative spine disorders entered the study. Baseline patients' characteristics and the abovementioned inflammatory markers were collected, and arithmetical means with standard deviation, area under the curve (AUC), thresholds, sensitivity, specificity, positive(+)likelihood ratio (LR), and negative(-)LR with corresponding 95% confidence interval(95%CI) were calculated and correlated with presence or absence of SSI. RESULTS: Nine patients suffered from a SSI, whereas the remaining 89 patients had a recurrent/adjacent-segment degenerative disorder without evidence of infection. The most significant parameter for diagnosing a SSI was serum IL-6 (cut-off value > 15.3 pg/ml, AUC = 0.954, SE = 85.7%, SP = 97.3%), followed by CRP (cut-off value = 0.8 mg/dl, AUC = 0.916, SE = 88.9%, SP = 84.5%) CONCLUSIONS: In the case of recurrent or new symptomatology following spinal surgery, serum IL-6 has the highest diagnostic potential for diagnosing spinal SSI.

Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas.

BACKGROUND: This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series. METHODS: This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers. RESULTS: For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1-5), and a median total implanted activity of 21.8 mCi (range 4.2-43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029). CONCLUSION: SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.

Extent and prognostic value of MGMT promotor methylation in glioma WHO grade II.

MGMT promotor methylation is associated with favourable outcome in high-grade glioma. In glioma WHO grade II, it is unclear whether the extent of MGMT promotor methylation and its prognostic role is independent from other molecular markers. We performed a retrospective analysis of 155 patients with glioma WHO grade II. First, all 155 patients were assigned to three molecular groups according to the 2016 WHO classification system: (1) oligodendroglioma, IDH-mutant and 1p19q co-deleted (n = 81); (2) astrocytoma, IDH-mutant and 1p19q non-codeleted (n = 54); (3) astrocytoma, IDH-wildtype (n = 20). MGMT promotor methylation was quantified using Sanger sequencing of the CpG sites 74-98 within the MGMT promotor region. Highest numbers of methylated CpG sites were found for oligodendroglioma, IDH-mutant and 1p19q co-deleted. When 1p19q co-deletion was absent, numbers of methylated CpG sites were higher in the presence of IDH-mutation. Accordingly, lowest numbers were seen in the IDH-wildtype subpopulation. In the entire cohort, larger numbers of methylated CpG sites were associated with favourable outcome. When analysed separately for the three WHO subgroups, a similar association was only retained in astrocytoma, IDH-wildtype. Collectively, extent of MGMT promotor methylation was strongly associated with other molecular markers and added prognostic information in astrocytoma, IDH-wildtype. Evaluation in prospective cohorts is warranted.