Minimally invasive tubular removal of spinal schwannoma and neurofibroma - a case series of 49 patients and review of the literature.

To evaluate the efficacy and safety of minimally invasive tubular removal of spinal schwannoma and neurofibroma. In this single-centre study, we retrospectively analysed 49 consecutive patients who underwent minimally invasive removal of a total of 51 benign spinal nerve sheath tumors using a non-expandable (n = 18) or expandable tubular retractor (n = 33) retractor system between June 2007 and December 2019. The extent of resection, surgical complications, neurological outcome, operative time, and estimated blood loss were recorded. Histopathology revealed 41 schwannomas and 10 neurofibromas. After a mean follow-up of 30.8 months, postoperative MRI showed gross total resection in 93.7%, and subtotal resection in 6.3% of the tumors. Three patients were lost to follow up. Of the subtotal resections, one was a schwannoma (2.4% subtotal resections in schwannomas) and two were neurofibromas (20.0% subtotal resections in neurofibromas). Intraspinal and paraspinal tumor localizations were equally accessible by minimally invasive tubular surgery. Conversion to open surgery was not required in any case. The mean operative time was 167 ± 68 min, and estimated blood loss was 138 ± 145 ml. We observed no major surgical complications. Spinal schwannoma and neurofibroma can be removed effectively and safely using a minimally invasive tubular approach, with satisfying extent of tumor resection comparable to the conventional open surgical technique and no increased risk for neurological deterioration.

Autologous platelet-rich fibrin (PRF) augmentation as an add-on therapy in deep surgical site infections (dSSIs) after instrumented spinal surgery: preliminary results of a single institution case series.

BACKGROUND: Deep surgical site infections (dSSIs) after instrumented spinal surgery pose major therapeutic challenges. Standard treatment involves surgical debridement, wound drainage, and long-term antibiotic administration. Autologous platelet-rich fibrin (PRF) constitutes a biomaterial obtained from patients' own blood that contains leukocytes, chemokines and growth factors boosting cicatrization. Due to favorable results reported from other surgical disciplines such as dentistry, orthopedics, maxillofacial and plastic surgery using PRF, the authors hypothesized that PRF augmentation will promote wound healing in dSSIs. OBJECTIVE: To report our preliminary results on the safety and efficacy of autologous-PRF as an add-on therapy on a pilot case series of persistent dSSI after instrumented spinal surgery. METHODS: Among the 293 patients who underwent dorsal decompression and stabilization of the cervical, thoracic, and lumbar spine due to degenerative diseases in our department, 12 patients (4%) presented persisting dSSI after standard wound debridement and antibiotic treatment. PRF augmentation was used during a second surgical revision as an add-on therapy to standard debridement. In all cases, the wound was primarily closed without drains. RESULTS: Wound healing was completed between 14 and 21 days after the second surgical revision in all patients. At a median follow-up of 8 months (range: 6 to 18 months), no recurrence of dSSI nor complications were encountered in any case. CONCLUSIONS: Our preliminary results suggest that PRF augmentation in persistent dSSI after instrumented spinal surgery appears to be a safe and effective strategy to promote wound healing. Prospective controlled studies are required to define the efficiency of PRF more clearly in both treating and preventing dSSI.

Case report: Concurrent low-volume subdural hematoma and ipsilateral ischemic stroke presenting as capsular warning syndrome: a complex case with anticoagulation dilemma and dual pathology.

Background: The simultaneous emergence of low-volume subdural hematoma and ipsilateral ischemic stroke in an atrial fibrillation patient who is under anticoagulation therapy is a rare and intricate clinical case. This report accentuates the diagnostic and treatment complexities associated with these consecutive neurological conditions. Case presentation: An 83 years-old male patient initially presented with acute dyspnea, raising the suspicion of pulmonary embolism. After exclusion of pulmonary embolism through CT angiography, the patient experienced a sudden onset of left-sided hemiparesis without prior history of head trauma but with chronic intake of apixaban due to atrial fibrillation. Subsequent cranial CT tomography revealed a small right parietal subdural hematoma. After reversal of the anticoagulation therapy, surgical evacuation of the subdural hematoma was successfully performed. However, in the postoperative period, the patient developed new neurological symptoms that could not be explained by the reduced size of the subdural hematoma on a follow-up CT scan. Cranial MRI revealed the coexistence of acute ischemic stroke in the right corona radiata. The recent surgical procedure precluded guideline-recommended stroke treatment. Discussion: This case underscores the complexities of diagnosing and treating concomitant small volume subdural hematoma and ischemic stroke, especially if the latter occurs in the corona radiata resulting in fluctuating symptoms known as "capsular warning syndrome." Reversal and secondary discontinuation of anticoagulant therapy for surgical intervention highlight the inherent risk of thrombotic events in anticoagulated patients. The development of tailored treatment strategies requires a multidisciplinary approach, and further research and guidelines are required in similar complex scenarios. Conclusion: The presence of both a small subdural hematoma and an ipsilateral ischemic stroke presenting as capsular warning syndrome in an anticoagulated patient highlights the intricacy of their care. This case calls for a comprehensive and collaborative strategy to address complicated clinical scenarios.

Safety, Sequelae, and Efficacy of Nerve Root Clipping in Patients With Spontaneous Spinal Cerebrospinal Fluid Leaks.

BACKGROUND AND OBJECTIVES: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of clinical symptoms, the most common being orthostatic headache. Lateral leaks (Type II) and direct CSF-venous fistulas (Type III) are a subgroup of spinal CSF leaks, representing about 1/3 of spinal CSF leaks. This study aimed to analyze the risk and efficacy of nerve root clipping in patients with Type II and Type III CSF leaks. METHODS: All consecutive patients with Type II and Type III CSF fistulas treated with nerve root clipping at our institution from May 2018 to December 2022 were included. Patients were evaluated for postoperative sensory motor deficits and neuropathic pain using the "Douleur Neuropathique 4" questionnaire, and the outcome was evaluated using the "Patient Global Impression of Change" and the return-to-work rate. RESULTS: A total of 40 patients were included, and the mean follow-up time was 22 months. According to the Patient Global Impression of Change, significant symptoms improvement was reported in 85% of patients. Over 87% of patients returned to work fully or partially. One patient experienced a low-grade motor deficit after T1-nerve root clipping. 2.5% of patients developed postoperative neuropathic pain requiring medical treatment under which they fully improved. Over 80% of patients developed dermatomal hypoesthesia, with no reported effect on quality of life. CONCLUSION: The surgical strategy of noneloquent nerve root clipping shows favorable outcomes and return-to-work rates. There are instances of neuropathic pain and dermatomal hypoesthesia with no significant morbidity. Despite the favorable outcome and low recurrence rate, nerve root-sparing surgical techniques should be further explored.

Double tubular minimally invasive spine surgery: a novel technique expands the surgical visual field during resection of intradural pathologies.

OBJECTIVE: A major challenge of a minimally invasive spinal approach (MIS) is maintaining freedom of maneuverability through small operative corridors. Unfortunately, during tubular resection of intradural pathologies, the durotomy and its accompanying tenting sutures offer a smaller operating window than the maximum surface of the tube's base. The objective of this study was to evaluate if a novel double tubular technique could expand the surgical visual field during MIS resection of intradural pathologies. METHODS: A total of 25 MIS resections of intradural extramedullary pathologies were included. A posterior tubular interlaminar fenestration was performed in all surgeries. A durotomy covering the whole diameter of the tubular base was the standard in all cases. After placement of two tenting sutures on each side of the durotomy and application of tension, the resulting surface of the achieved dura fenestration was measured after optical analysis of the intraoperative video. In the next step, a second tube, 2 mm thinner than and the same length as the first, was inserted telescopically into the first tube, resulting an angulated fulcrum effect on the tenting sutures. RESULTS: Optical surface analysis of the dura fenestration before and after the second tubular insertion verified a significant widening of the visual field of 43.1% (mean 18.84 mm2, 95% CI 16.8-20.8, p value < 0.001). There were no ruptured tenting sutures through the increased tension. Postoperative MRIs verified complete resection of the pathologies. CONCLUSIONS: Inserting a second tube telescopically during posterior minimally invasive tubular spinal intradural surgery leads to an angulated fulcrum effect on the dura tenting sutures which consequently increases the surface of the dura fenestration and induces a meaningful widening of the visual field.

Long-Term Results after Multilevel Fusion of the Cervical Spine and the Cervicothoracic Junction: To Bridge or Not To Bridge?

OBJECTIVE: For patients with multilevel degenerative cervical myelopathy, laminectomy and fusion are widely accepted techniques for ameliorating the disorder. However, the idea of whether one should bridge the cervicothoracic junction to prevent instrument failure or adjacent segment disease has been a subject of controversial discussion. In the present study, we compared the incidence of these complications and the revision rates in multilevel fusions extending to C7 or T1-T3. METHODS: In the present single-center, retrospective cohort study, patients with multilevel degenerative cervical myelopathy treated with laminectomy and fusion to C7 or T1-T3 from 2004 to 2016 were included for evaluation. The primary outcome measure was radiologically proven complications at the most caudal level or the adjacent spinal fusion level. RESULTS: Laminectomy and multilevel fusion were performed in 84 patients. After applying the exclusion criteria, 20 patients with fusion to C7 (treated from 2004 to 2012; follow-up, 124.6 ± 10.6 months) and 38 patients with fusion to T1-T3 (treated from 2008 to 2016; follow-up, 58.2 ± 15.7 months) were evaluated. The incidence of complications at the most caudal or adjacent level of fusion was twice as high (P = 0.087; NS) in the C7 group (11 of 20; 55.0%) compared with the T1-T3 group (11 of 38; 28.9%). In the C7 group, 9 of the 20 patients (45.0%) had required revision surgery compared with 2 of 38 patients (5.3%) in the T1-T3 group (P = 0.001). CONCLUSIONS: We found that fewer revisions were necessary if the fusion had extended to the thoracic spine. Thus, we recommend bridging the cervicothoracic junction when fusion starts at C0-C3.

Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.

BACKGROUND: Collagen cross-links contribute to the mechanical resilience of the intervertebral disc (IVD). UVA-light-activated riboflavin-induced collagen crosslinking (UVA-CXL) is a well-established and effective ophthalmological intervention that increases the mechanical rigidity of the collagen-rich corneal matrix in Keratoconus. This study explores the feasibility, safety and efficacy of translating this intervention in reinforcing the IVD. METHODS: Annulus fibrosus (AF) cells were isolated from bovine IVDs and treated with different combinations of riboflavin (RF) concentrations (0.05-8 mM) and UVA light intensities (0.3-4 mW/cm2). Metabolic activity (resazurin assay), cell viability (TUNEL assay), and gene expression of apoptosis regulators C-FOS and PT5 were assessed immediately and 24 hours after treatment. Biomechanical effects of UVA-CXL on IVDs were measured by indentation analysis of changes in the instantaneous modulus and by peel-force delamination strength analysis of the AF prior and after treatment. RESULTS: Different intensities of UVA did not impair the metabolic activity of AF cells. However, RF affected metabolic activity (p < 0.001). PT53 expression was similar in all RF conditions tested while C-FOS expression decreased 24 hours after treatment. Twenty-four hours after treatment, no apoptotic cells were observed in any condition tested. Biomechanical characterizations showed a significant increase in the annular peel strength of the UVA-CXL group, when compared to controls of UVA and RF alone (p < 0.05). UVA-CXL treated IVDs showed up to 152% higher (p < 0.001) instantaneous modulus values compared to the untreated control. CONCLUSION: This is the first study on UVA-CXL treatment of IVD. It induced significantly increased delamination strength and instantaneous modulus indentation values in intact IVD samples in a structure-function relationship. RF concentrations and UVA intensities utilized in ophthalmological clinical protocols were well tolerated by the AF cells. Our findings suggest that UVA-CXL may be a promising tool to reinforce the IVD matrix.

Radiation Exposure to Scrub Nurse, Assistant Surgeon, and Anesthetist in Minimally Invasive Spinal Fusion Surgery Comparing 2D Conventional Fluoroscopy With 3D Fluoroscopy-based Navigation: A Randomized Controlled Trial.

STUDY DESIGN: A randomized controlled trial. OBJECTIVE: To compare the radiation exposure with the scrub nurse, assistant surgeon, and anesthetist during minimally invasive transforaminal lumbar interbody fusion using conventional 2-dimensional (2D) fluoroscopy or 3D fluoroscopy-based navigation. SUMMARY OF BACKGROUND DATA: Minimally invasive spinal fusion techniques are related to higher radiation exposures compared with open techniques. Especially the routinely exposed surgical staff faces the risks of increased radiation exposure. METHODS: In total, 41 patients with planned monosegmental minimally invasive transforaminal lumbar interbody fusion were randomized into the intraoperative imaging techniques 2D fluoroscopy or 3D navigation. Eye lens and film dosemeters were attached to defined locations of the scrub nurse, assistant surgeon, and anesthetist. Mann-Whitney U and Wilcoxon-matched pairs signed-rank test were used to compare dosemeter readings. This study was registered with the German Clinical Trials Register (DRKS00004514). RESULTS: The radiation exposure per surgery was low for the scrub nurse, assistant surgeon, and anesthetist in both the 2D fluoroscopy and 3D navigation groups. The maximum average value of 0.057±0.031 mSv was measured on the unprotected chest of the assistant surgeon and was thus slightly above the lower detection limit of the dosemeters (0.044 mSv). The annual occupational dose limit would be exceeded at the earliest after 571 operations for the unprotected eye lens of the assistant surgeon. CONCLUSIONS: Minimally invasive lumbar fusion surgery is possible with comparatively low radiation exposure to the assisting operating room personnel without exceeding the annual maximum occupational radiation exposure. However, there is no definite dose value below which ionizing radiation poses no risk. Consequently, radiation sparing work routines should be strictly followed.

Noninvasive patient tracker mask for spinal 3D navigation: does the required large-volume 3D scan involve a considerably increased radiation exposure?

OBJECTIVE: Intraoperative 3D imaging and navigation is increasingly used for minimally invasive spine surgery. A novel, noninvasive patient tracker that is adhered as a mask on the skin for 3D navigation necessitates a larger intraoperative 3D image set for appropriate referencing. This enlarged 3D image data set can be acquired by a state-of-the-art 3D C-arm device that is equipped with a large flat-panel detector. However, the presumably associated higher radiation exposure to the patient has essentially not yet been investigated and is therefore the objective of this study. METHODS: Patients were retrospectively included if a thoracolumbar 3D scan was performed intraoperatively between 2016 and 2019 using a 3D C-arm with a large 30 × 30-cm flat-panel detector (3D scan volume 4096 cm3) or a 3D C-arm with a smaller 20 × 20-cm flat-panel detector (3D scan volume 2097 cm3), and the dose area product was available for the 3D scan. Additionally, the fluoroscopy time and the number of fluoroscopic images per 3D scan, as well as the BMI of the patients, were recorded. RESULTS: The authors compared 62 intraoperative thoracolumbar 3D scans using the 3D C-arm with a large flat-panel detector and 12 3D scans using the 3D C-arm with a small flat-panel detector. Overall, the 3D C-arm with a large flat-panel detector required more fluoroscopic images per scan (mean 389.0 ± 8.4 vs 117.0 ± 4.6, p < 0.0001), leading to a significantly higher dose area product (mean 1028.6 ± 767.9 vs 457.1 ± 118.9 cGy × cm2, p = 0.0044). CONCLUSIONS: The novel, noninvasive patient tracker mask facilitates intraoperative 3D navigation while eliminating the need for an additional skin incision with detachment of the autochthonous muscles. However, the use of this patient tracker mask requires a larger intraoperative 3D image data set for accurate registration, resulting in a 2.25 times higher radiation exposure to the patient. The use of the patient tracker mask should thus be based on an individual decision, especially taking into considering the radiation exposure and extent of instrumentation.

How Safe Is Minimally Invasive Transforaminal Lumbar Interbody Fusion for Octogenarians?: A Perioperative Complication Analysis.

BACKGROUND: Technical advances in minimally invasive spine surgery have reduced blood loss, access trauma, and postoperative length of stay. However, operating on the susceptible group of octogenarians still poses a dilemma because of a plethora of age-related comorbidities. The aim of this study was to investigate the safety of minimally invasive surgery (MIS) transforaminal lumbar interbody fusion (TLIF) in octogenarians. METHODS: We conducted a retrospective single-center study of all patients over 80 years of age who, between March 2009 and February 2014, had undergone MIS TLIF. The primary outcome was recorded major and minor complications within 30 days of surgery. RESULTS: Twenty-one patients with an average age of 84.1 ± 2.7 years underwent MIS TLIF in 31 levels for degenerative lumbar disk disease with intolerable pain after failure of conservative treatment. Of the patients, 33.3% showed no perioperative complications. In the remaining 66.7%, 6 major complications and 24 minor complications occurred within 30 days of surgery. Two of these patients died within 30 days of surgery because of sepsis and pulmonary embolism (mortality rate 9.5%). CONCLUSIONS: Our study spotlighted the susceptible group of octogenarians and evaluated the safety of MIS TLIF. The perioperative morbidity for octogenarians undergoing MIS TLIF is substantial and even higher than for patients over 65 years of age. Two thirds of patients in this subgroup suffer at least 1 complication. The 30-day mortality rate was 9.5%. Therefore, it is advisable for these patients to exploit all available conservative options prior to surgery.

Infrared attenuated total reflection spectroscopic surface analysis of bovine-tail intervertebral discs after UV-light-activated riboflavin-induced collagen cross-linking.

The tensile strength of the intervertebral disc (IVD) is mainly maintained by collagen cross-links. Loss of collagen cross-linking combined with other age-related degenerative processes contributes to tissue weakening, biomechanical failure, disc herniation and pain. Exogenous collagen cross-linking has been identified as an effective therapeutic approach for restoring IVD tensile strength. The current state-of-the-art method to assess the extent of collagen cross-linking in tissues requires destructive procedures and high-performance liquid chromatography. In this study, we investigated the utility of infrared attenuated total reflection (IR-ATR) spectroscopy as a nondestructive analytical strategy to rapidly evaluate the extent of UV-light-activated riboflavin (B2)-induced collagen cross-linking in bovine IVD samples. Thirty-five fresh bovine-tail IVD samples were equally divided into five treatment groups: (a) untreated, (b) cell culture medium Dulbecco's Modified Eagle's Medium only, (c) B2 only, (d) UV-light only and (e) UV-light-B2. A total of 674 measurements have been acquired, and were analyzed via partial least squares discriminant analysis. This classification scheme unambiguously identified individual classes with a sensitivity >91% and specificity >92%. The obtained results demonstrate that IR-ATR spectroscopy reliably differentiates between different treatment categories, and promises an excellent tool for potential in vivo, nondestructive and real-time assessment of exogenous IVD cross-linking.

Piezosurgery-, neuroendoscopy-, and neuronavigation-assisted intracranial approach for removal of a recurrent petrous apex cholesteatoma: technical note.

Current approaches for resection of petrous bone cholesteatomas (PBCs), such as canal wall up (closed) and canal wall down (open) mastoidectomies, in the pediatric population present recurrence rates ranging between 17% and 70% with a high rate of postoperative complications involving hearing loss and facial nerve weakness. This technical note illustrates an alternative intracranial approach that was used in combination with the techniques of piezoelectric surgery, neuroendoscopy, and neuronavigation for safe and effective removal in a difficult pediatric case of recurrent PBC. The third recurrence of a PBC in a 14-year-old girl was diagnosed by CT and MRI. A retrosigmoid approach gave access to the petrous apex, allowing for the safe and complete removal of the lesion and decompression of the facial nerve and internal carotid artery. The intraoperative implementation of piezoelectric surgery, neuronavigation, neuroendoscopy, and neuromonitoring ensured better intraoperative visualization, safer bone removal, and preservation of nerve function, facilitating a macroscopically total resection of the pathology without additional neurological damage of the adjacent tissues. Cholesteatoma extension could be clearly verified by intraoperative neuronavigation. Neuroendoscopy and piezoelectric surgery provided good support in the safe bone removal in close vicinity to neurovascular structures and in full vision inside the cholesteatoma cavity beyond the line of sight of the microscope. Hearing and facial nerve function could be preserved. The presented intracranial retrosigmoid approach combined with multiple intraoperative assisting techniques proved to be effective for the safe and complete removal of recurrent PBC, providing excellent intraoperative visualization and the possibility of preserving cranial nerve function.

Incidental Durotomy in Open Versus Tubular Revision Microdiscectomy: A Retrospective Controlled Study on Incidence, Management, and Outcome.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare the incidence, management, and outcome of incidental durotomy in revision microdiscectomy with open and minimal-access surgery. SUMMARY OF BACKGROUND DATA: Incidental durotomy occurs with a variable incidence of 3%-27% in spine surgery. The highest rate occurs in revision microdiscectomy. The intraoperative and postoperative management of dural tears varies in the literature and the definite impact on clinical outcome has to be clarified. METHODS: This is a retrospective study of medical records of 135 patients who underwent revision microdiscectomy, divided into 2 subgroups: OPEN (n=82) versus minimal-access surgery (MINI, n=53). Occurrence of intraoperative dural tears, intraoperative and postoperative management of durotomy, and clinical outcomes, according to MacNab criteria, were retrospectively examined. Statistical comparisons for categorical values between groups were accomplished using the 2-tailed Fisher exact test. P-values <0.05 were considered to be statistically significant. RESULTS: The incidence of durotomy in group OPEN was 19.5% (n=16/82) and in group MINI 17.0% (n=9/53) (P=0.822). The majority of durotomies (23/25) were repaired with an absorbable fibrin sealant patch alone. Postoperative cerebrospinal fluid fistula occurred only in 1 case of the OPEN group and was treated with lumbar drainage without the need for a reoperation. Patients with durotomy of the MINI group tended to have better outcome compared with those of the OPEN group without being statistically significant. CONCLUSIONS: The incidence of durotomy and postoperative cerebrospinal fluid fistula in lumbar revision microdiscectomy does not significantly differ between minimal-access and standard open procedures. The application of a fibrin sealant patch alone is an effective strategy for dural repair in revision lumbar microdiscectomy.

Verteporfin inhibits growth of human glioma in vitro without light activation.

Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.

Minimally invasive tubular microdiscectomy for recurrent lumbar disc herniation.

OBJECTIVE: The aim of the study was to investigate the safety and efficacy of minimally invasive tubular microdiscectomy for the treatment of recurrent lumbar disc herniation (LDH). As opposed to endoscopic techniques, namely microendoscopic and endoscopic transforaminal discectomy, this microscopically assisted technique has never been used for the treatment of recurrent LDH. METHODS: Thirty consecutive patients who underwent minimally invasive tubular microdiscectomy for recurrent LDH were included in the study. The preoperative and postoperative visual analog scale (VAS) scores for pain, the clinical outcome according to modified Macnab criteria, and complications were analyzed retrospectively. The minimum follow-up was 1.5 years. Student t-test with paired samples was used for the statistical comparison of pre- and postoperative VAS scores. A p value < 0.05 was considered to be statistically significant. RESULTS: The mean operating time was 90 ± 35 minutes. The VAS score for leg pain was significantly reduced from 5.9 ± 2.1 preoperatively to 1.7 ± 1.3 postoperatively (p < 0.001). The overall success rate (excellent or good outcome according to Macnab criteria) was 90%. Incidental durotomy occurred in 5 patients (16.7%) without neurological consequences, CSF fistula, or negative influence to the clinical outcome. Instability occurred in 2 patients (6.7%). CONCLUSIONS: The clinical outcome of minimally invasive tubular microdiscectomy is comparable to the reported success rates of other minimally invasive techniques. The dural tear rate is not associated to higher morbidity or worse outcome. The technique is an equally effective and safe treatment option for recurrent LDH.

Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma.

Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS) to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes. Our model identified Annexin A2 (ANXA2) as a novel methylation-controlled positive regulator of the mesenchymal subtype. Subsequent evaluation in two independent cohorts established ANXA2 expression as a prognostic factor that is dependent on ANXA2 promoter methylation. ANXA2 knockdown in primary glioblastoma stem cell-like cultures suppressed known mesenchymal master regulators, and abrogated cell proliferation and invasion. Our results place ANXA2 at the apex of a regulatory cascade that determines glioblastoma mesenchymal transformation and validate aSICS as a general methodology to uncover regulators of cancer subtypes.

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme.

The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligodendrocytic and neural development. For normalised creatine (nCr), a group with low nCr was linked to the mesenchymal subtype, while high nCr could be assigned to the proneural subtype. Moreover, clustering of normalised glutamine and glutamate (nGlx) revealed two groups, one with high nGlx being attributed to the neural subtype, and one with low nGlx associated with the classical subtype. Hence, the metabolites nNAA, nCr, and nGlx correlate with a specific gene expression pattern reflecting the previously described subtypes of GBM. Moreover high nNAA was associated with better clinical prognosis, whereas patients with lower nNAA revealed a shorter progression-free survival (PFS).