Publications by authors named "Alp Ozpinar"

67 Publications

Operative Outcomes After Cervical Diffuse Idiopathic Skeletal Hyperostosis Fracture in the Elderly.

Int J Spine Surg 2022 Jun;16(3):435-441

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Background: Cervical diffuse idiopathic skeletal hyperostosis (DISH) fractures are frequently unstable and carry significant risk of neurologic injury and death. Most patients with DISH fractures are elderly (>70 years) with significant comorbidities. We assessed factors that contribute to outcomes in elderly patients with cervical DISH fractures.

Methods: Elderly patients with cervical DISH fractures from 2008 to 2017 were included in this retrospective multi-institutional cohort study. Predictor variables included injury level, surgical approach, preinjury comorbidities, American Society of Anesthesiologists (ASA) score, American Spinal Injury Association (ASIA) impairment scale grade, preoperative anticoagulation status, and the subaxial cervical spine injury classification system (SLIC) score. Univariate and multivariate analyses were utilized to identify factors associated with 30-day mortality and ambulatory status at discharge.

Results: A total of 48 patients, mean age 74.7 years old (range 60-96), underwent cervical fixation for DISH fractures. Average SLIC score was 6.30 ± 1.2 (range 5-8), and most frequent fracture level was at C6 to -C7 (31.3%) followed by C7-T1 (25.0%). Forty (83.3%) patients underwent posterior fixation, 7 (14.6%) with anterior fixation, and 1 (2.1%) had combined approach. Ten (20.4%) patients died within 30 days of surgery. Multivariate analysis demonstrated that poorer preoperative ASIA grade (OR 2.35, = 0.003, CI = 1.33-4.14) and ASA score >3 ( = 0.027) had increased risk of being nonambulatory at discharge. Higher SLIC score was associated with increased 30-day mortality ( = 0.021, CI = 1.20-9.60).

Conclusions: Cervical DISH fractures can be highly unstable, for which instrumentation and fixation are indicated. Surgical decision-making should focus on preoperative ASIA grade, SLIC score, and ASA score.

Clinical Relevance: The study is relevant due to an aging poulation predisposed to cervical DISH fractures.

Level Of Evidence: 4:
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http://dx.doi.org/10.14444/8252DOI Listing
June 2022

Evolution of polyetheretherketone (PEEK) and titanium interbody devices for spinal procedures: a comprehensive review of the literature.

Eur Spine J 2022 Jun 10. Epub 2022 Jun 10.

Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA, 15213, USA.

Introduction: Interbody fusion is commonly utilized for arthrodesis and stability among patients undergoing spine surgery. Over the last few decades, interbody device materials, such as titanium and polyetheretherketone (PEEK), have been replacing traditional autografts and allografts for interbody fusion. As such, with the exponential growth of bioengineering, a large variety cage surface technologies exist. Different combinations of cage component materials and surface modifications have been created to optimize interbody constructs for surgical use. This review aims to provide a comprehensive overview of common surface technologies, their performance in the clinical setting, and recent modifications and material combinations.

Materials And Methods: We performed a comprehensive review of the literature on titanium and PEEK as medical devices between 1964 and 2021. We searched five major databases, resulting in 4974 records. Articles were screened for inclusion manually by two independent reviewers, resulting in 237 articles included for review.

Conclusion: Interbody devices have rapidly evolved over the last few decades. Biomaterial and biomechanical modifications have allowed for continued design optimization. While titanium has a high osseointegrative capacity, it also has a high elastic modulus and is radio-opaque. PEEK, on the other hand, has a lower elastic modulus and is radiolucent, though PEEK has poor osseointegrative capacity. Surface modifications, material development advancements, and hybrid material devices have been utilized in search of an optimal spinal implant which maximizes the advantages and minimizes the disadvantages of each interbody material.
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http://dx.doi.org/10.1007/s00586-022-07272-1DOI Listing
June 2022

MGMT in glial carcinogenesis. Roles from prevention to treatment.

Eur J Cancer Prev 2022 Jun 3. Epub 2022 Jun 3.

Department of Biochemistry, Acibadem University.

Many investigations exist regarding the effect of the DNA repair enzyme MGMT (O6-methylguanine- DNA-methyltransferase)-encoding gene methylation on the antineoplasticity of temozolomide in glioblastoma patients. However, there exist surprisingly lesser studies regarding the associations between MGMT enzyme biochemistry with glial carcinogenesis. MGMT involves in risk of malignancies associated with ionizing radiation, smoking, exposure to polycyclic aromatic hydrocarbons, chlorinated solvents, vinylchloride and hairdyes. All these factors are also proposed to link with gliomagenesis, yet MGMT interactions with these carcinogens in gliomagenesis are not studied yet. In future, MGMT sequencing may be employed in vulnerable populations working in industries associated with exposure to these carcinogens to develop preventive strategies. Given that MGMT is involved in DNA repair, a polymorphism may simultaneously modify the risk of gliomas while enhancing temozolomide cytotoxicity in both marrow and tumor cells.
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http://dx.doi.org/10.1097/CEJ.0000000000000746DOI Listing
June 2022

Combining locoregional CAR-T cells, autologous  allogeneic tumor lysate vaccination and levamisole in treatment of glioblastoma.

Immunopharmacol Immunotoxicol 2022 Jun 14:1-12. Epub 2022 Jun 14.

Department of Biochemistry, Acibadem University, Istanbul, Turkey.

Glioblastoma multiforme (GBM) is an aggressive brain malignancy and harbors a microenvironment limiting immune cells activity. CAR-T cells are being tested in the treatment of cancers and there exist reports which demonstrate dramatic regression of multicentric GBMs following intrathecal treatment with CAR-T cells. In this article, a triple approach for immune treatment of GBM is proposed. First, GBM tumor specimens for each patient will be saved and cultured to obtain tumor lysates. Then, levamisole will be applied, which possesses immunostimulating, anti-glycolytic, and anti-angiogenic features. Following priming the immune system, GBM patients will be injected with lysates of their own tumor cells plus lysates from a GBM cell line, U251. After 3 months of this treatment, CAR-T cells (transduced with IL13Rα2-CAR will be applied intratumoral approach. As such, genetically-modified and native immunocytes may 'meet' in the vicinity of deeply-invading tumor cells and demonstrate greater efficacy cell-cell interactions. By this, a self-propagating cyclic process - a cancer-immunity cycle - may be initiated to eradicate cancer cells.
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http://dx.doi.org/10.1080/08923973.2022.2086136DOI Listing
June 2022

Subsidence after lateral lumbar interbody fusion using a 3D-printed porous titanium interbody cage: single-institution case series.

J Neurosurg Spine 2022 May 20:1-7. Epub 2022 May 20.

1Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh.

Objective: Cage subsidence is a well-known phenomenon after lateral lumbar interbody fusion (LLIF), occurring in 10%-20% of cases. A 3D-printed porous titanium (pTi) cage has a stiffness that mimics the modulus of elasticity of native vertebrae, which reduces stress at the bone-hardware interface, lowering the risk of subsidence. In this study, the authors evaluated their institutional rate of subsidence and resultant reoperation in patients who underwent LLIF using a 3D-printed pTi interbody cage.

Methods: This is a retrospective case series of consecutive adult patients who underwent LLIF using pTi cages from 2018 to 2020. Demographic and clinical characteristics including age, sex, bone mineral density, smoking status, diabetes, steroid use, number of fusion levels, posterior instrumentation, and graft size were collected. The Marchi subsidence grade was determined at the time of last follow-up. Outcome measures of interest were subsidence and resultant reoperation. Univariable logistic regression analysis was performed to assess the extent to which clinical and operative characteristics were associated with Marchi grade I-III subsidence. Significance was assessed at p < 0.05.

Results: Fifty-five patients (38 with degenerative disc disease and 17 with adult spinal deformity) were treated with 97 pTi interbody cages with a mean follow-up of 18 months. The mean age was 63.6 ± 10.1 years, 60% of patients were female, and 36% of patients had osteopenia or osteoporosis. Patients most commonly underwent single-level LLIF (58.2%). Sixteen patients (29.1%) had posterior instrumentation. The subsidence grade distribution was as follows: 89 (92%) grade 0, 5 (5%) grade I, 2 (2%) grade II, and 1 (1%) grade III. No patients who were active or prior smokers and no patients with posterior instrumentation experienced graft subsidence. No clinical or operative characteristics were significantly associated with graft subsidence. One patient (1.8%) required reoperation because of subsidence.

Conclusions: In this institutional case series, subsidence of pTi intervertebral cages after LLIF occurred in 8% of operated levels, 3% of which were grade II or III. Only 1 patient required reoperation. These reported rates are lower than those reported for polyetheretherketone implants. Further studies are necessary to compare the impact of these cage materials on subsidence after LLIF.
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http://dx.doi.org/10.3171/2022.4.SPINE2245DOI Listing
May 2022

3D printing applications in spine surgery: an evidence-based assessment toward personalized patient care.

Eur Spine J 2022 Jul 19;31(7):1682-1690. Epub 2022 May 19.

Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA, USA.

Purpose: Spine surgery entails a wide spectrum of complicated pathologies. Over the years, numerous assistive tools have been introduced to the modern neurosurgeon's armamentarium including neuronavigation and visualization technologies. In this review, we aimed to summarize the available data on 3D printing applications in spine surgery as well as an assessment of the future implications of 3D printing.

Methods: We performed a comprehensive review of the literature on 3D printing applications in spine surgery.

Results: Over the past decade, 3D printing and additive manufacturing applications, which allow for increased precision and customizability, have gained significant traction, particularly spine surgery. 3D printing applications in spine surgery were initially limited to preoperative visualization, as 3D printing had been primarily used to produce preoperative models of patient-specific deformities or spinal tumors. More recently, 3D printing has been used intraoperatively in the form of 3D customizable implants and personalized screw guides.

Conclusions: Despite promising preliminary results, the applications of 3D printing are so recent that the available data regarding these new technologies in spine surgery remains scarce, especially data related to long-term outcomes.
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http://dx.doi.org/10.1007/s00586-022-07250-7DOI Listing
July 2022

Direct Pars Repair with Cannulated Screws in Adults: A Case Series and Systematic Literature Review.

World Neurosurg 2022 Jul 30;163:e263-e274. Epub 2022 Mar 30.

Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA. Electronic address:

Objective: Lumbar spondylolysis occurs in 5%-8% of adults. This study aimed to report clinical and radiographic outcomes of direct pars repair in adults with lumbar spondylolysis.

Methods: We conducted a retrospective review of all patients treated for lumbar spondylolysis via open fracture reduction and direct pars repair with cannulated screws using a lag technique. Demographics, clinical presentation, perioperative and intraoperative imaging, and postoperative data were collected. We subsequently performed a systematic review to describe radiographic and clinical outcomes following direct pars repair.

Results: Three patients were identified (mean age 40.3 years; range, 21-72 years; 2 male). All patients had bilateral L5 pars fractures treated via open, direct repair with cannulated screws. There were no intraoperative complications. Length of stay was <24 hours for each patient. All patients reported back/radicular symptom relief and returned to full-time manual labor by latest follow-up. Noncontrast lumbar computed tomography performed 14-20 months postoperatively confirmed that all patients had good bilateral screw placement without fracture. Two patients (21 and 28 years old at surgery) had evidence of fusion across fracture sites, while 1 patient exhibited radiolucency around the screws and no progression of spondylolisthesis. Additionally, we reviewed 8210 articles and included 15 in a systematic review of direct pars repair. Fusion rates were 67%-100%, with improved average Oswestry Disability Index and visual analog scale back pain scores by latest follow-up.

Conclusions: Lumbar spondylolysis treatment with open fracture reduction and direct pars repair with cannulated screws in adults is safe and may result in mechanical back/radicular pain relief, even in the absence of radiographic fusion.
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http://dx.doi.org/10.1016/j.wneu.2022.03.107DOI Listing
July 2022

A hypothetical proposal to employ meperidine and tamoxifen in treatment of glioblastoma. Role of P-glycoprotein, ceramide and metabolic pathways.

Clin Neurol Neurosurg 2022 04 16;215:107208. Epub 2022 Mar 16.

Department of Biochemistry, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Istanbul, Turkey.

Meperidine (pethidine) is a µ-opioid receptor (MOR) agonist widely used in the treatment of cancer pain. While MOR agonists in experimental models have demonstrated both pro- and antitumorigenic properties, meperidine has unique features which may be predominantly anticancer in nature. Meperidine both inhibits NMDA (N-methyl-D-Aspartate) receptors, which are involved in the progression of glioblastoma, and blocks NADH:Ubiquinone Oxidoreductase, which may hinder mitochondrial respiration. In the developing embryonic neural tissue, meperidine reduces cell proliferation around the neural tube and lowers the expression of the B RE (brain and reproductive organ-expressed). This is notable given that the B RE gene is implicated in cancer chemoresistance and gliomagenesis. Further, meperidine inhibits P-glycoprotein, which is involved in cancer multidrug resistance and the degradation of the sphingolipid backbone, ceramide. By enhancing the pro-autophagic and pro-apoptotic ceramide levels in cancer cells, meperidine stimulates cell death and reverses multidrug resistance. Tamoxifen, a safe medication employed in the treatment of breast cancer, directly blocks P-glycoprotein and boosts levels of ceramide both via inhibition of glycosylceramide synthase and ceramidase. Further, tamoxifen blocks NMDA-neurotoxicity and therefore it may act synergistically with meperidine in reducing glioblastoma progression associated with NMDA-activation. Finally, tamoxifen blocks glycolysis which may enhance the mitochondrial-blocking activity of meperidine to shut down energy metabolism of glioblastoma cells. Because of these properties, we believe that the combination of meperidine and tamoxifen merits study in cell culture and animal models to investigate a potential synergistic relationship in the treatment of glioblastoma.
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http://dx.doi.org/10.1016/j.clineuro.2022.107208DOI Listing
April 2022

A Novel 5-Aminolevulinic Acid-Enabled Surgical Loupe System-A Consecutive Brain Tumor Series of 11 Cases.

Oper Neurosurg (Hagerstown) 2022 05;22(5):298-304

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Background: The concept of maximally safe resection (MSR) has been shown to improve clinical outcomes in the treatment of high-grade gliomas (HGGs). To achieve MSR, surgical adjuncts such as functional imaging, neuronavigation, intraoperative mapping, ultrasound, and fluorescence-guided surgery are routinely used. 5-Aminolevulinic acid (5-ALA) is an oral agent that has been increasingly adopted in fluorescence-guided resection of HGG. In randomized clinical trials of 5-ALA, it has been shown to increase the extent of resection and progression-free survival in HGG. Current commercially available 5-ALA detection systems are all microscope-based and can sometimes be cumbersome to use.

Objective: To present our experience using a novel 5-ALA-enabled surgical loupe system.

Methods: 5-ALA-enabled loupes were used in 11 consecutive patients with either suspected HGG on magnetic resonance imaging or recurrence of known lesions. Lesion appearance was examined under white light, 5-ALA loupes, and a 5-ALA microscope. Tumor specimens were checked for fluorescence and sent for pathologic examination.

Results: In our experience, a 5-ALA-enabled surgical loupe system offers excellent visualization of 5-ALA in patients with HGG. In 10 of 11 patients, fluorescent tissue was confirmed to be high-grade glioma by pathology. In 1 patient, tissue was not fluorescent, and final pathology was World Health Organization grade I meningioma.

Conclusion: A 5-ALA-enabled surgical loupe system offers excellent intraoperative visualization of 5-ALA fluorescence in HGG and can be a viable surgical adjunct for achieving MSR of HGG.
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http://dx.doi.org/10.1227/ons.0000000000000141DOI Listing
May 2022

Longitudinal Analysis of Peripheral Nerve Surgery Training: Comparison of Neurosurgery to Plastic and Orthopedic Surgery.

World Neurosurg 2022 Jun 30;162:e41-e48. Epub 2022 Jan 30.

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. Electronic address:

Background: Residents in multiple surgical specialties are trained to perform peripheral nerve surgery (PNS), but the extent of exposure to this field varies among specialties. This study evaluates trends in volume of PNS performed during residency for neurologic surgery trainees compared to those in plastic and orthopedic surgery between 2009 and 2019.

Methods: We queried ACGME for neurologic, plastic, and orthopedic surgery resident case-logs and compared mean number of PNS between graduating residents of each specialty using a one-way analysis of variance test. Linear regression was utilized to determine trends within and across the specialties over the study period.

Results: Neurosurgery residents (24.76 ± 3.41) performed significantly fewer PNS than their counterparts in orthopedic (54.56 ± 6.85) and plastic surgery (71.96 ± 12.20), P < 0.001. Residents in neurologic surgery reported over 1.5-fold as many cases as their ACGME-required minimum, in contrast to plastic (2.5-fold) and orthopedic (5-fold). Plastics residents (3.46 cases/year) demonstrated the greatest longitudinal increase in PNS, followed by neurosurgery residents (0.81 cases/year). PNS accounted for a mean of 5.81% of neurosurgery resident cases, 4.20% of plastic surgery resident cases, and 2.98% of orthopedic surgery resident cases (P < 0.001).

Conclusions: Neurosurgery residents exceeded the required minimum number of PNS and were increasingly more exposed to PNS. However, compared with their counterparts in orthopedic and plastic surgery, neurosurgery residents performed significantly fewer cases. Exposure for neurosurgery residents remains unchanged over the study period while plastic surgery residents experienced an increase in case volume. The deficiency in exposure for neurosurgical residents must be addressed to harness interest and proficiency in PNS.
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http://dx.doi.org/10.1016/j.wneu.2022.01.094DOI Listing
June 2022

Patient perception of scoliosis correction surgery on Instagram.

Neurosurg Focus 2021 11;51(5):E6

Objective: Patient feedback surveys provide important insight into patient outcomes, satisfaction, and perioperative needs. Recent critiques have questioned provider-initiated surveys and their capacity to accurately gauge patient perspectives due to intrinsic biases created by question framing. In this study, the authors sought to evaluate provider-independent, patient-controlled social media Instagram posts in order to better understand the patient experience following scoliosis correction surgery.

Methods: Twitter and Instagram were queried for posts with two tagged indicators, #scoliosissurgery or @scoliosissurgery, resulting in no relevant Twitter posts and 25,000 Instagram posts. Of the initial search, 24,500 Instagram posts that did not directly involve the patient's own experience were eliminated. Posts were analyzed and coded for the following criteria: the gender of the patient, preoperative or postoperative timing discussed in the post, and classified themes related to the patient's experiences with scoliosis correction surgery.

Results: Females made 87.6% of the Instagram posts about their experience following scoliosis correction surgery. The initial postoperative stage of surgery was mentioned in 7.6% of Instagram posts. The most common theme on Instagram involved offering or seeking online support from other patients, which constituted 85.2% of all posts. Other common themes included concern about the surgical scar (31.8%), discussing the results of treatment (28.8%), and relief regarding results (21.2%).

Conclusions: Social media provided a platform to analyze unprompted feedback from patients. Patients were most concerned with their scoliosis correction surgery in the period of time 2 weeks or more after surgery. Themes that were most commonly found on Instagram posts were offering or seeking online support from other patients and concern about the surgical scar. Patient-controlled social media platforms, like Instagram, may provide a useful mechanism for healthcare providers to understand the patient experience following scoliosis correction surgery. Such platforms may help in evaluating postoperative satisfaction and improving postoperative quality of care.
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http://dx.doi.org/10.3171/2021.8.FOCUS201015DOI Listing
November 2021

Does Variceal Drainage Affect Arteriovenous Malformation Obliteration and Hemorrhage Rates After Stereotactic Radiosurgery? A Case-Matched Analysis.

Neurosurgery 2021 09;89(4):680-685

Department of Neurological Surgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Background: Stereotactic radiosurgery (SRS) is widely accepted as a minimally invasive alternative to surgery in the management of arteriovenous malformations (AVMs). Dilated AVM outflow veins or varices may be caused by high-flow or partial outflow obstruction, which may increase the risk of a hemorrhage before or after SRS.

Objective: To compare the obliteration and hemorrhage risks in patients with and without AVM varices (AVMv).

Methods: From our prospective database of 1012 AVM patients who underwent Gamma Knife® (Elekta) SRS, we identified 103 patients with AVMv, and 847 patients without varices. The median follow-up was 52 mo. Balancing variable score matching was performed to compare obliteration and hemorrhage rates between the 2 groups.

Results: Obliteration rates in the AVMv group were 38% at 3 yr, 65% at 4 yr, and 70% at 5 yr. Patients with an AVMv had no difference in the final obliteration rate compared to patients who did not have variceal drainage (P = .35). Actuarial hemorrhage after SRS in the matched patients with AVMv was 4.9%, 13%, and 13.7%, at 1, 3, and 5 yr, respectively. The rate of hemorrhage in the group with no varix was 2.9%, 5.4%, and 9.1% at 1, 3, and 5 yr, respectively (P = .14).

Conclusion: The presence of AVM variceal venous drainage did not affect the obliteration rate and did not confer a higher risk of a subsequent hemorrhage both before and after SRS.
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http://dx.doi.org/10.1093/neuros/nyab256DOI Listing
September 2021

Incidence of adjacent-segment surgery following stand-alone lateral lumbar interbody fusion.

J Neurosurg Spine 2021 Jun 18:1-5. Epub 2021 Jun 18.

Objective: Adjacent-segment disease (ASD) requiring operative intervention is a relatively common long-term consequence of lumbar fusion surgery. Although the incidence of ASD requiring reoperation is well described for traditional posterior lumbar approaches (2.5%-3.9% per year), it remains poorly characterized for stand-alone lateral lumbar interbody fusion (LLIF). In this study, the authors report their institutional experience with ASD requiring reoperation after LLIF over an extended follow-up period of 4 years.

Methods: Medical records were reviewed for 276 consecutive patients who underwent stand-alone LLIF by a single surgeon for degenerative spinal disorders. Inclusion criteria (single-stage, stand-alone LLIF without posterior supplementation, with no prior lumbar instrumentation, and a minimum of 4 years of follow-up) were met by 182 patients, who were analyzed for operative ASD incidence (per-year rate), demographics, and Oswestry Disability Index (ODI) score. Operative ASD was strictly defined as new-onset pathology following index surgery at directly adjacent levels to the prior construct. Operative, rather than symptomatic or radiographic, ASD was analyzed to provide a consistent and impactful endpoint while avoiding retrospective diagnosis.

Results: The study cohort of 182 patients had an operative ASD rate of 3.3% (n = 6 procedures) over 4 years of follow-up, for an incidence on Kaplan-Meier survival analysis of 0.88% (95% CI 0.67%-1.09%) per year. In comparing patients with operative ASD with those without, there were no significant differences in mean age (53.7 vs 56.2 years), male sex (33.3% vs 44.9%), smoking status (16.7% vs 25.0%), or number of levels fused (mean 1.33 vs 1.46). The operative ASD cohort had a greater mean BMI (37.3 vs 30.2, p < 0.01). Operative ASD patients had lower baseline ODI scores (33.8 vs 48.3, p = 0.02); however, no difference was observed in ODI at 6 weeks (34.0 vs 39.0) or 3 months (16.0 vs 32.8) postoperatively.

Conclusions: The incidence of ASD in LLIF for degenerative lumbar etiologies in this cohort was 0.88% (95% CI 0.67%-1.09%) per year. Meanwhile, the reported reoperation rates for ASD in posterior spinal approaches was 2.5% to 3.9% per year, which implies that LLIF may be preferable for well-selected patients.
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http://dx.doi.org/10.3171/2020.12.SPINE201218DOI Listing
June 2021

Load-Sharing Classification Score as Supplemental Grading System in the Decision-Making Process for Patients With Thoracolumbar Injury Classification and Severity 4.

Neurosurgery 2021 08;89(3):428-434

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Background: Patients with Thoracolumbar Injury Classification and Severity (TLICS) score of 4 fall into a gray zone between surgical and conservative management. The integrity of posterior ligamentous complex (PLC) evaluated by magnetic resonance imaging (MRI) contributes to surgical decision-making. Load-sharing classification (LSC) may provide a modifier to further guide decision-making in these patients.

Objective: To evaluate associations between LSC score and MRI acquisition, compromise of PLC on MRI, and surgical intervention in TLICS 4 patients.

Methods: A cohort of 111 neurologically intact patients with isolated thoracolumbar burst fracture with TLICS 4 was evaluated. LSC score was determined based on degree of comminution (1-3), apposition (1-3), and kyphosis (1-3), total composite score of 3 to 9.

Results: Overall, 44 patients underwent MRI, 15 had PLC injury, and 32 (28.8%) underwent surgery. LSC score was higher in patients who had an MRI (median 6 vs 3, P < .001) and patients who had surgery (median 7 vs 4, P < .001). In univariate logistic regression, LSC score was associated with MRI acquisition (odds ratio [OR] 1.7; 1.32-2.12; P < .001), presence of PLC injury on MRI (OR 1.5; 1.2-2.0; P = .002) and, in multivariate logistic regression, undergoing surgical intervention (OR 3.7; 2.3-5.9; P < .001), independent of MRI or PLC injury.

Conclusion: LSC score in neurologically intact patients with isolated thoracolumbar burst fracture with TLICS 4 was independently associated with operative intervention. The application of LSC may further guide decision-making in this patient group.
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http://dx.doi.org/10.1093/neuros/nyab179DOI Listing
August 2021

Safety of lateral access to the concave side for adult spinal deformity.

J Neurosurg Spine 2021 May 14:1-5. Epub 2021 May 14.

1Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and.

Objective: Minimally invasive surgery (MIS) techniques, particularly lateral lumbar interbody fusion (LLIF), have become increasingly popular for adult spinal deformity (ASD) correction. Much discussion has been had regarding theoretical and clinical advantages to addressing coronal curvature from the convex versus concave side of the curve. In this study, the authors aimed to broadly evaluate the clinical outcomes of addressing ASD with circumferential MIS (cMIS) techniques while accessing the lumbar coronal curvature from the concave side.

Methods: A multi-institution, retrospective chart and radiographic review was performed for all ASD patients with at least a 10° curvature, as defined by the Scoliosis Research Society, who underwent cMIS correction. The data collected included convex versus concave access to the coronal curve, durable or sensory femoral nerve injury lasting longer than 6 weeks, vascular injury, visceral injury, and any additional major complication, with at least a 2-year follow-up. Neither health-related quality-of-life metrics nor spinopelvic parameters were included within the scope of this study.

Results: A total of 152 patients with ASD treated with cMIS correction via lateral access were identified and analyzed. Of these, 126 (82.9%) were approached from the concave side and 26 (17.1%) were approached from the convex side. In the concave group, 1 (0.8%) motor and 4 (3.2%) sensory deficit cases remained at 6 weeks after the operation. No vascular, visceral, or catastrophic intraoperative injuries were encountered in the concave group. Of the 26 patients in the convex group, 2 (7.7%) experienced motor deficits lasting longer than 6 weeks and 5 (19.2%) had lower-extremity sensory deficits.

Conclusions: It has been reported that lateral access to the convex side is associated with similar clinical and radiographic outcomes with fewer complications when compared with access to the concave side. Advantages to approaching the lumbar spine from the concave side include using one incision to access multiple levels, breaking the operative table to assist with curvature correction, easier access to the L4-5 disc space, the ability to release the contracted side, and, often, avoidance of the need to access or traverse the thoracic cavity. This study illustrates the largest reported cohort of concave access for cMIS scoliosis correction; few postoperative sensory and motor deficits were found.
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http://dx.doi.org/10.3171/2020.10.SPINE191270DOI Listing
May 2021

Safety and Efficacy of Balloon Kyphoplasty for Vertebral Fractures With Posterior Wall Disruption.

Int J Spine Surg 2021 Apr 1;15(2):353-358. Epub 2021 Apr 1.

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Percutaneous balloon kyphoplasty (BK) is widely accepted as both a safe and effective method for the treatment of symptomatic benign vertebral compression fractures (VCFs) of the thoracic and lumbar spines. A disruption in the posterior wall of the affected vertebra is often considered to be a relative or an absolute contraindication to BK. This study was performed to determine the safety as well as the efficacy of BK for vertebral body compression fractures associated with posterior wall disruption.

Methods: This was a retrospective, nonrandomized clinical cohort investigation of patients with VCF and posterior wall disruption treated with BK between 2010 and 2018. All cases were performed using a bipedicular technique. Each case was examined for cement leakage, anterior vertebral body height restoration, improvement in pain (determined by VAS) from baseline and 6-week postprocedure, and clinical sequelae from cement leakage.

Results: Ninety-eight consecutive patients with 157 VCF levels who underwent BK were evaluated. There was a significant improvement in anterior vertebral height, vertebral wedge angle, and local kyphotic angle in all cases. The mean preoperative VAS improved from 8.7 preprocedure to 2.5 postprocedure ( = .001). There were 14 (9%) cases with asymptomatic cement leakage outside of the vertebral body, and no patients experienced postprocedure neurological symptoms at the 6-week follow up.

Conclusions: BK in the setting of posterior wall disruption was found to be a safe and highly effective treatment for patients with benign compression fractures. Posterior wall disruption should not be considered an absolute contraindication to BK.
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http://dx.doi.org/10.14444/8046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059384PMC
April 2021

The utility of routine head CT for hemorrhage surveillance in post-craniotomy patients undergoing anticoagulation for venous thromboembolism.

J Clin Neurosci 2021 Mar 15;85:78-83. Epub 2021 Jan 15.

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States. Electronic address:

Anticoagulation for postoperative venous thromboembolism (VTE) may infer a higher risk of intracranial hemorrhage. We treat patients with VTE using slowly titrating intravenous heparin drip without bolus. When PTT is greater than 60 s, a head CT is obtained to monitor for the development of a intracranial hemorrhage before transition to oral anticoagulation. We evaluated the utility of routine surveillance head CT to monitor for intracranial hemorrhage during anticoagulation. This is a case series of neurosurgical patients in an academic quaternary hospital who developed a VTE after cranial procedures between 2007 and 2017. Over 11,000 patients were screened for the study. Patients' demographics data, surgical indication, PTT at the time of surveillance CT head, surveillance CT head findings, and patient's clinical course were reviewed. A total of 83 patients were included. Three patients (3.6%) developed a new subclinical hemorrhage on CT head imaging while on heparin drip. Interval CT head showed stable hemorrhage in all patients. Heparin drip was stopped in two patients and they both progressed from DVT to pulmonary embolism: one patient died due to cardiac arrest, the other patient was transitioned to oral anticoagulation. In the third patient heparin drip was continued uneventfully and transitioned to oral anticoagulation with no further clinical sequalae. Surveillance CT while on heparin drip for VTE management detected subclinical intracranial hemorrhage in a small subset of patients. Patients whose anticoagulation was stopped had progression of VTE. Undertreatment of VTE in the presence of subclinical hemorrhage may lead to significant morbidity and mortality.
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http://dx.doi.org/10.1016/j.jocn.2020.12.010DOI Listing
March 2021

Neurosurgical and neuro-immunological management of IgG4-related hypertrophic sclerosing pachymeningitis. A literature survey and discussion of a unique index case.

Clin Neurol Neurosurg 2021 01 1;200:106342. Epub 2020 Nov 1.

Department of Pathology, Yeditepe University, Istanbul, Turkey.

Background: Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients' serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community.

Methods: MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder.

Results: MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment.

Conclusions: IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.
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http://dx.doi.org/10.1016/j.clineuro.2020.106342DOI Listing
January 2021

PPARδ and its ligand erucic acid may act anti-tumoral, neuroprotective, and myelin protective in neuroblastoma, glioblastoma, and Parkinson's disease.

Mol Aspects Med 2021 04 20;78:100871. Epub 2020 Jul 20.

Department of Biochemistry, Acibadem University, Istanbul, Turkey.

In this review study, we focus on potential benefits of the transcription factor PPARδ and its ligand erucic acid (EA) in management of neuroectodermal tumors and Parkinson's Disease. PPARδ is a nuclear receptor and transcription factor that induces myelination, promotes oligodendroglial and neuronal differentiation, and possess anti-neuroinflammatory properties. While both pro-tumorigenic and anti-tumorigenic effects have been described for PPARδ, we propose that PPARδ may perform a predominantly anticancer role in tumors originating from the neuroectoderm. PPARδ ligand-activation via oleic acid and GW501516, or overexpression of PPARδ, elicits profound antitumor actions in neuroblastoma and melanoma. In glioblastomas, there is evidence indicating a differentiation failure of O2A (oligodendroglial-astrocytic biprogenitor) cells and it has been shown that EA reduced DNA synthesis in C6 rat glioblastoma spheroid cultures in clinically achievable concentrations. EA is a ω9 fatty acid which is being used in the treatment of adrenoleukodystrophy. EA is widely consumed in Asian countries via ingestion of cruciferous vegetables including mustard and rapeseed oil. EA also exerts antioxidant and anti-inflammatory activities. Recent studies of Parkinson's Disease (PD) have implicated demyelination, white matter pathology, oligodendroglial injury, and neural inflammation in the underlying pathophysiology. In the rotenone PD model in rats, PPARδ ligand GW501516 saves dopaminergic neurons during injury induced by chemical toxins and improves behavioral functioning in PD via alleviation of endoplasmic reticulum stress. PPARδ agonists also reduce the NLRP3 inflammasome-associated neural inflammation in the MPTP PD model in mice. Herein, we propose that PPARδ and its ligand EA highly deserve to be studied in animal models of neuroblastoma, glioblastoma, and PD.
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http://dx.doi.org/10.1016/j.mam.2020.100871DOI Listing
April 2021

Relationship Between Preoperative Opioid Use and Postoperative Pain in Patients Undergoing Minimally Invasive Stand-Alone Lateral Lumbar Interbody Fusion.

Neurosurgery 2020 11;87(6):1167-1173

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Opioid use in the management of pain secondary to spinal disorders has grown significantly in the United States. However, preoperative opioid use may complicate recovery in patients undergoing surgical procedures.

Objective: To test our hypothesis that prolonged preoperative opioid use may lead to poorer patient outcomes following minimally invasive stand-alone lateral lumbar interbody fusion (LLIF) for lumbar degenerative disc disease.

Methods: A consecutive series of patients from a single institution undergoing LLIF between December 2009 and January 2017 was retrospectively analyzed. Patients were categorized according to the presence or absence of prescribed preoperative opioid use for at least 3 mo. Outcomes included the Oswestry Disability Index (ODI), visual analog scale (VAS), and Short Form 36 Physical and Mental Summary Scores (SF-36 PCS, SF-36 MCS).

Results: Of 107 patients, 57 (53.1%) were prescribed preoperative opioids. There was no significant difference in preoperative ODI, VAS score, SF-36 PCS, or SF-36 MCS between opioid use groups. Mean postoperative ODI was greater in patients with preoperative opioid use at 41.7 ± 16.9 vs 22.2 ± 16.0 (P = .002). Mean postoperative VAS score was greater in patients prescribed preoperative opioids, while magnitude of decrease in VAS score was greater in opioid-naïve patients (P = .001). Postoperative SF-36 PCS was 33.1 ± 10.6 in the opioid use group compared to 43.7 ± 13.1 in the nonuse group (P = .001).

Conclusion: Following LLIF, patients prescribed preoperative opioids had increased postoperative lumbar pain, disability, and subjective pain.
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http://dx.doi.org/10.1093/neuros/nyaa207DOI Listing
November 2020

Impact of endplate-implant area mismatch on rates and grades of subsidence following stand-alone lateral lumbar interbody fusion: an analysis of 623 levels.

J Neurosurg Spine 2020 Mar 6:1-5. Epub 2020 Mar 6.

Objective: Stand-alone lateral lumbar interbody fusion (LLIF) is a useful minimally invasive approach for select spinal disorders, but implant subsidence may occur in up to 30% of patients. Previous studies have suggested that wider implants reduce the subsidence rate. This study aimed to evaluate whether a mismatch of the endplate and implant area can predict the rate and grade of implant subsidence.

Methods: The authors conducted a retrospective review of prospectively collected data on consecutive patients who underwent stand-alone LLIF between July 2008 and June 2015; 297 patients (623 surgical levels) met inclusion criteria. Imaging studies were examined to grade graft subsidence according to Marchi criteria. Thirty patients had radiographic evidence of implant subsidence. The endplates above and below the implant were measured.

Results: A total of 30 patients with implant subsidence were identified. Of these patients, 6 had Marchi grade 0, 4 had grade I, 12 had grade II, and 8 had grade III implant subsidence. There was no statistically significant correlation between the endplate-implant area mismatch and subsidence grade or incidence. There was also no correlation between endplate-implant width and length mismatch and subsidence grade or incidence. However, there was a strong correlation between the usage of the 18-mm-wide implants and the development of higher-grade subsidence (p = 0.002) necessitating surgery. There was no significant association between the degree of mismatch or Marchi subsidence grade and the presence of postoperative radiculopathy. Of the 8 patients with 18-mm implants demonstrating radiographic subsidence, 5 (62.5%) required reoperation. Of the 22 patients with 22-mm implants demonstrating radiographic subsidence, 13 (59.1%) required reoperation.

Conclusions: There was no correlation between endplate-implant area, width, or length mismatch and Marchi subsidence grade for stand-alone LLIF. There was also no correlation between either endplate-implant mismatch or Marchi subsidence grade and postoperative radiculopathy. The data do suggest that the use of 18-mm-wide implants in stand-alone LLIF may increase the risk of developing high-grade subsidence necessitating reoperation compared to the use of 22-mm-wide implants.
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http://dx.doi.org/10.3171/2020.1.SPINE19776DOI Listing
March 2020

Hypothesis: Could Hepatitis B vaccine act as an immune adjuvant in glioblastoma? Clues to conduct further epidemiological analyses.

Int Immunopharmacol 2020 Apr 19;81:106038. Epub 2019 Nov 19.

Department of Neurosurgery, Acibadem University, İstanbul, Turkey.

A failure of neurodevelopmental differentiation at the level of oligodendroglial-astrocytic biprogenitors (O2A) is shown to be involved in the pathogenesis of both multiple sclerosis (MS) and glioblastoma multiforme (GBM). In this review article, we suggest that certain antigens of Hepatitis B Virus (HBV) and HBV-Vaccine (HBV-V) could act as immune stimulants in GBM treatment based on several lines of evidence. HBV-Vs may cause rare but prominent neuroimmune side effects including demyelination and multiple sclerosis, which may be associated with HBV-proteins creating antigenic mimicry of oligodendroglial progenitors. The combined prevalance of HBV and Hepatitis C Virus-carrier state is less in patients with brain tumors compared to healthy subjects. Furthermore, within the population of patients with brain tumors, the prevalence is even about two times lesser in GBM in comparison to those with a diagnosis of meningioma. Although indirectly, this epidemiological data may indicate that the immune response triggered against hepadnavirus antigens would eliminate aberrantly differentiating O2A progenitor cells giving rise to GBMs. Moreover, Hepatitis B surface antigen-antibody variable domain is among the top 100 differentially expressed transcripts in fresh frozen and formalin-fixed paraffin-embeded specimens obtained from pediatric GBM tissues in comparison to the control brain tissues. However, the provided evidence is still premature and we think that HBV-V warrants investigation first by epidemiological studies and then by animal experiments to determine whether it reduces the risk of GBM and whether it could slow GBM growth via immune stimulation.
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http://dx.doi.org/10.1016/j.intimp.2019.106038DOI Listing
April 2020

Erucic acid, a nutritional PPARδ-ligand may influence Huntington's disease pathogenesis.

Metab Brain Dis 2020 01 17;35(1):1-9. Epub 2019 Oct 17.

Department of Neurosurgery, Pittsburgh University, Pittsburgh, PA, USA.

Increasing recent evidence suggests a key role of oligodendroglial injury and demyelination in the pathophysiology of Huntington's Disease (HD) and the transcription factor PPARδ is critical for oligodendroglial regeneration and myelination. PPARδ directly involves in the pathogenesis of HD and treatment with a brain-permeable PPARδ-agonist (KD3010) alleviates its severity in mice. Erucic acid (EA) is also a PPARδ-ligand ω9 fatty acid which is highly consumed in Asian countries through ingesting cruciferous vegetables such as rapeseed (Brassica napus) and indian mustard (Brassica juncea). EA is also an ingredient of Lorenzo's oil employed in the medical treatment of adrenoleukodystrophy and can be converted to nervonic acid, a component of myelin. HD pathogenesis also involves oxidative and inflammatory injury and EA exerts antioxidative and antiinflammatory efficacies including inhibition of thrombin and elastase. Consumption of rapeseed, indian mustard, and Canola oils (containing EA) improves cognitive parameters in animal models, as well as treatment with pure EA. Moreover, erucamide, an endogenous EA-amide derivative regulating angiogenesis and water balance, exerts antidepressive and anxiolytic effects in mice. Hitherto, no study has investigated the therapeutic potential of EA in HD and we believe that it strongly merits to be studied in animal models of HD as a potential therapeutic.
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http://dx.doi.org/10.1007/s11011-019-00500-6DOI Listing
January 2020

Noscapine, a Non-addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma.

Neurochem Res 2019 Aug 10;44(8):1796-1806. Epub 2019 Jul 10.

Department of Neurosurgery, Acibadem Hospital, Istanbul, Turkey.

Noscapine is a phthalide isoquinoline alkaloid that easily traverses the blood brain barrier and has been used for years as an antitussive agent with high safety. Despite binding opioid receptors, noscapine lacks significant hypnotic and euphoric effects rendering it safe in terms of addictive potential. In 1954, Hans Lettré first described noscapine as a mitotic poison. The drug was later tested for cancer treatment in the early 1960's, yet no effect was observed likely as a result of its short biological half-life and limited water solubility. Since 1998, it has regained interest thanks to studies from Emory University, which showed its anticancer activity in animal models with negligible toxicity. In contrast to other microtubule-inhibitors, noscapine does not affect the total intracellular tubulin polymer mass. Instead, it forces the microtubules to spend an increased amount of time in a paused state leading to arrest in mitosis and subsequently inducing mitotic slippage/mitotic catastrophe/apoptosis. In experimental models, noscapine does not induce peripheral neuropathy, which is common with other microtubule inhibitors. Noscapine also inhibits tumor growth and enhances cancer chemosensitivity via selective blockage of NF-κB, an important transcription factor in glioblastoma pathogenesis. Due to their anticancer activities and high penetration through the blood-brain barrier, noscapine analogues strongly deserve further study in various animal models of glioblastoma as potential candidates for future patient therapy.
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http://dx.doi.org/10.1007/s11064-019-02837-xDOI Listing
August 2019

Could hepatitis B vaccine act as an adjuvant to lower risk and relapses of cancer?

Clin Exp Pharmacol Physiol 2019 08 7;46(8):694-704. Epub 2019 May 7.

Department of Neurosurgery, Acibadem University, İstanbul, Turkey.

In this review article, we hypothesize that Hepatitis B Virus Vaccine (HBV-V) and certain antigens of Hepatitis B Virus (HBV) could act as anticancer immunoadjuvants in addition to their role of preventing HBV-associated liver cancer. Evidence suggests that in animal breast cancer and melanoma models, combining hepatitis B-surface antigen (HBsAg) with other cancer antigens resulted in enhanced antitumour activity. HBsAg shares antigenic mimicry with healthy and malignant cells including squamous epithelia, thymic epithelia, bladder- and colon cancer cells. There exist anecdotal reports and small case series about spontaneous remission of leukaemias and neuroblastoma following acute HBV-infection. Recent studies also exist showing HBV-carrier state is a good prognostic factor for intrahepatic cholangiocarcinoma. Further epidemiological studies and animal experiments are necessary whether HBV-Vs exert additional immunoadjuvant benefits besides lowering the risk of liver cancer.
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http://dx.doi.org/10.1111/1440-1681.13096DOI Listing
August 2019

From epidemiology and neurometabolism to treatment: Vitamin D in pathogenesis of glioblastoma Multiforme (GBM) and a proposal for Vitamin D + all-trans retinoic acid + Temozolomide combination in treatment of GBM.

Metab Brain Dis 2019 06 1;34(3):687-704. Epub 2019 Apr 1.

Department of Medical Biochemistry, Acibadem University, Istanbul, Turkey.

Here we review tumoricidal efficacy of Vitamin D analogues in glioblastoma multiforme (GBM) and potential synergisms with retinoic acid and temozolomide based on epidemiological and cellular studies. Epidemiological data suggest that winter birth is associated with higher risk of GBM, and GBM debulking in the winter enhanced mortality, which may relate with lower exposure to sunlight essential to convert cholecalciferol to Vitamin D. Comparative studies on blood bank specimens revealed that higher prediagnosis levels of calcidiol are associated with lower risk of GBM in elderly men. Supplemental Vitamin D reduced mortality in GBM patients in comparison to nonusers. Expression of Vitamin D Receptor is associated with a good prognosis in GBM. Conversely, Vitamin D increases glial tumor synthesis of neutrophins NGF and NT-3, the low affinity neurotrophin receptor p75NTR, IL-6 and VEGF, which may enhance glioma growth. Antitumor synergisms between temozolomide and Vitamin D and Vitamin D with Vitamin A derivatives were observed. Hence, we hypothesize that Calcitriol + ATRA (All-Trans Retinoic Acid) + Temozolomide - CAT combination might be a safer approach to benefit from Vitamin D in the management of high-grade glial tumors. Adding acetazolomide to this protocol may reduce the risk of pseudotumor cerebri, as both Vitamin D and Vitamin A excess may cause intracranial hypertension; this approach may provide further benefit as acetazolomide also exhibits anticancer activity.
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http://dx.doi.org/10.1007/s11011-019-00412-5DOI Listing
June 2019

Methenamine's journey of 160 years: Repurposal of an old urinary antiseptic for treatment and hypoxic radiosensitization of cancers and glioblastoma.

Clin Exp Pharmacol Physiol 2019 05 27;46(5):407-412. Epub 2019 Feb 27.

Department of Neurosurgery, Acibadem University, Istanbul, Turkey.

Methenamine (hexamethylenetetramine, hexamine, urotropine) is a compound discovered in 1859, which is still currently being used as a urinary antiseptic. Methenamine is highly soluble in water and polar solvents, and its molecular constitution is similar to adamantane compounds with tetrahedral cage like structure. In acidic conditions, methenamine decomposes to formaldehyde and ammonia. Recently, methenamine has gained a renewal of interest due to antibiotic-resistant bacteria urinary tract infections; interestingly, bacteria cannot gain resistance to formaldehyde. In 1968, David and Burkitt reported remarkable regression of four Burkitt Lymphoma patients in eight subjects who were treated with septicemine (a solution containing 6.3 g of methenamine iodomethylate and 1 g of methenamine sodium benzoate in 100 cc distilled water). Unfortunately, these striking observations did not gain interest in the medical community; despite experimental models that showed that methenamine synergized with hyperthermia, radiation, and chemotherapy to block cancer growth. As the hypoxic core of tumours have an acidic pH, it would be plausible to expect that methenamine would selectively target dormant, non-proliferative, and treatment-resistant cancer clones in large tumours. Moreover, previous data suggests that methenamine can be safely used intravenously and for treatment of infections of the central nervous system. It may therefore be an effective adjuvant in treatment of systemic cancers and glioblastoma.
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http://dx.doi.org/10.1111/1440-1681.13070DOI Listing
May 2019

Salvage Stereotactic Radiosurgery in Breast Cancer Patients with Multiple Brain Metastases.

World Neurosurg 2019 05 31;125:e479-e486. Epub 2019 Jan 31.

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Background: The overall survival rates for breast cancer are increasing due to controlled brain disease and improved systemic treatments. This study examined neurologic outcomes, tumor control, and survival data in breast cancer patients with multiple brain metastases and who required salvage stereotactic radiosurgery (SRS) for recurrent breast cancer brain metastases.

Methods: The study included 231 patients with a primary diagnosis of breast cancer who underwent SRS for more than 1 brain metastases from May 1993 and July 2007. Survival analyses via univariate and multivariate Cox regression demonstrated interactions between survival and predictor values including Karnofsky Performance Scale, Recursive Partitioning Analysis Class, number of brain metastases, whole-brain radiotherapy (WBRT), immunotherapy, and chemotherapy.

Results: Of the 231 patients, the survival rate was 53% at 1 year and 26% at 5 years from initial SRS. Controlled systemic disease, adjuvant chemotherapy, and Recursive Partitioning Analysis class II were significant predictors of increased survival, while WBRT was a significant predictor of decreased survival. The median survival in patients who received WBRT after SRS was 11 months versus 23 months in those who did not. The local tumor control rate at initial follow-up was 95%. Of these, 40% of patients underwent additional brain SRS. Following salvage SRS, 8% of patients developed symptomatic adverse radiation events; however, the development of symptomatic adverse radiation events had no effect on patient survival.

Conclusions: This report indicated that both initial and salvage SRS procedures in breast cancer patients with multiple brain metastases are effective for local control of intracranial disease while minimizing adverse radiation effects.
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http://dx.doi.org/10.1016/j.wneu.2019.01.108DOI Listing
May 2019

Validation of an extrinsic compression and early ambulation protocol after diagnostic transfemoral cerebral angiography: a 5-year prospective series.

J Neurointerv Surg 2019 Aug 23;11(8):837-840. Epub 2019 Jan 23.

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background And Purpose: Access-site complications constitute a substantial portion of the morbidity associated with transfemoral cerebral angiography, yet no standardized protocol exists for femoral closure and practice patterns vary widely. The objective of this single-arm prospective cohort study was to validate the efficacy and safety of a standardized femoral closure strategy for all diagnostic angiography, regardless of antiplatelet regimen.

Methods: A single-arm, prospective study was designed enrolling consecutive patients undergoing diagnostic transfemoral cerebral angiography by a single neurointerventional surgeon from March 2013 - March 2018. The closure protocol consisted of 20 minutes of manual compression to the site of arterial access and 2 hours of bedrest. The primary outcome was hematoma or oozing after manual compression. Demographic, clinic, and laboratory data were collected and analyzed, and patients were stratified by antiplatelet use.

Results: Of 525 angiograms, 263 (50.1%) were on patients taking antiplatelet medication, with 66 (12.6%) on dual antiplatelet regimens. Five patients (0.95% of all patients) met the primary outcome: in all five cases, there was no further oozing or enlarging hematoma after the additional compression period. There were not significant differences in primary outcome in groups stratified by antiplatelet use, and there were no instances of delayed hematoma, pseudoaneurysm, or arteriovenous fistula.

Conclusion: In this single-arm cohort study of 525 consecutive transfemoral angiograms with a standardized extrinsic compression protocol, hemostasis was achieved without complication in >99% regardless of antiplatelet strategy. This protocol is effective and safe for diagnostic transfemoral angiography regardless of a patient's antiplatelet use.
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http://dx.doi.org/10.1136/neurintsurg-2018-014572DOI Listing
August 2019

Gamma Knife Radiosurgery for Trigeminal Neuralgia Caused by a Cavernous Malformation: Case Report and Literature Review.

Stereotact Funct Neurosurg 2018 16;96(6):412-415. Epub 2019 Jan 16.

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Objective: Trigeminal neuralgia (TN) related to a brainstem cavernous malformation (CM) is a rare entity. We present the first radiosurgical management of a patient with TN secondary to a CM.

Clinical Presentation: An 80-year-old female presented with a 33-year history of progressively severe TN refractory to medications. Imaging confirmed a solitary CM located at the pontine dorsal root entry zone of cranial nerve 5.

Treatment: Stereotactic radiosurgery of the trigeminal nerve was performed using the Leksell gamma knife. A single 4-mm isocenter of radiation was focused on the trigeminal nerve and a maximum dose of 80 Gy (40 Gy at the 50% isodose line) was delivered to the nerve.

Results: At 1 year, the patient noted that the severe pain attacks had been reduced by 75%, although a background lingering discomfort persisted. Pain suppression medications had been significantly reduced to lamotrigine 100 mg twice daily. Her preoperative distribution of sensory dysfunction mildly increased.

Conclusion: For medically refractory TN related to a CM, radiosurgery of the afferent nerve may ameliorate pain without a major decrease in sensation. The more than 30-year history of pain in our patient may have reduced the chance of more significant pain relief.
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http://dx.doi.org/10.1159/000495476DOI Listing
October 2019
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