Polymethyl Methacrylate Augmentation is Associated with Reduced Cerebrospinal Fluid Leak After Supratentorial Craniotomy: A Retrospective Cohort Study

Polymethyl Methacrylate Augmentation is Associated with Reduced Cerebrospinal Fluid Leak After Supratentorial Craniotomy: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Polymethyl Methacrylate Augmentation is Associated with Reduced Cerebrospinal Fluid Leak After Supratentorial Craniotomy: A Retrospective Cohort Study Hüseyin Biçeroğlu, Elif Ezgi Çenberlitaş, Bilal Bahadır Akbulut, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8903756/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Cerebrospinal fluid leakage is a frequent complication following craniotomy, associated with morbidity, prolonged hospitalization, and increased healthcare costs. This study aimed to evaluate whether augmentation of craniotomy closure with polymethyl methacrylate reduces postoperative CSF leak rates compared to conventional closure techniques in supratentorial cases. Methods We performed a retrospective, single‑center cohort study including consecutive adult patients who underwent supratentorial craniotomy between January 2018 and August 2024. Beginning in September 2020, PMMA augmentation was routinely applied to fill residual interosseous gaps after bone‑flap fixation, enabling a temporal cohort comparison. The primary endpoint was CSF leakage within 12 months. Multivariate logistic regression was used to identify independent predictors while accounting for potential confounders related to patient characteristics, pathology, and surgical variables. Results A total of 186 patients were analyzed (135 PMMA; 51 no PMMA). CSF leakage occurred in 9 patients (4.8%). Leakage was less frequent in the PMMA group (2.2% vs. 11.8%, p = 0.014), corresponding to an absolute risk reduction of 9.6% and a number‑needed‑to‑treat of approximately 10. PMMA use remained independently associated with lower leak risk (OR 0.17, 95% CI 0.03–0.92, p = 0.039). No increase in wound complications, shunt procedures, or readmissions attributable to PMMA was observed. Conclusion PMMA augmentation during supratentorial craniotomy closure was associated with a reduced rate of postoperative CSF leakage without evidence of added morbidity. These findings suggest that gap‑filling augmentation may represent a useful adjunct in selected patients; however, prospective multicenter validation is warranted. craniotomy cerebrospinal fluid leak polymethyl methacrylate cranioplasty postoperative complications Figures Figure 1 Figure 2 Figure 3 Introduction Cerebrospinal fluid (CSF) leakage is one of the most frequent complications following cranial surgery [ 2 , 6 ], with reported rates ranging from 2.9% to 6.4% across all craniotomies [ 7 ]. Such leaks are associated with prolonged hospitalization, increased healthcare costs, wound infections, and the risk of meningitis, thereby contributing substantially to postoperative morbidity [ 8 , 13 ]. Consequently, considerable efforts have been made to develop closure techniques that can minimize CSF leakage. Standard methods typically involve watertight dural closure, use of dural substitutes or sealants, and secure fixation of the bone flap with plates and screws [ 4 , 14 ]. Despite these measures, interosseous gaps between bone edges may still remain after flap fixation. These residual gaps can provide a potential pathway for CSF egress. Polymethyl methacrylate (PMMA) has long been used in neurosurgery for cranioplasty and skull reconstruction due to its biocompatibility, stability, and adaptability [ 1 , 3 ]. Its application to fill bone gaps at the time of craniotomy closure, however, has not been systematically evaluated. After approximating the dural edges with primary suturing, followed by duraplasty using Tisseel and an artificial dural substitute, the bone flap was fixed with plates and screws. The remaining interosseous gaps were then filled with PMMA to eliminate residual voids and reinforce the closure (Fig. 1 ). The present study aimed to assess whether PMMA augmentation reduces postoperative CSF leak rates compared with conventional craniotomy techniques. Secondary endpoints included wound complications, CSF diversion procedures, and hospital readmissions. Systematic evaluation in supratentorial craniotomy has been limited thus providing a novel contribution to the neurosurgical literature. Methods Study design and patient selection: This retrospective cohort study included all consecutive adult patients who underwent supratentorial craniotomy performed by the same neurosurgical team at a university hospital between January 2018 and August 2024. Due to the transition to a new electronic medical record system in 2017, only patients operated on after January 2018 were included in this study. Only patients with a minimum follow-up of 12 months were included. The study period was truncated in August 2024 to ensure a minimum follow-up of 12 months for all included patients. Both primary and revision surgeries were included. Exclusion criteria were procedures involving the posterior fossa or cerebellum; however, occipital supratentorial cases were retained. The inclusion and exclusion process of the study cohort is summarized in Fig. 2 . Based on accumulating clinical experience and encouraging reports from the literature, our neurosurgical team at a university hospital introduced PMMA augmentation as a routine practice in September 2020. This provided a unique opportunity to compare outcomes before and after the adoption of PMMA augmentation within the same surgical practice. Surgical technique and materials: All procedures were performed by the same neurosurgical team using a standardized closure protocol consisting of primary dural approximation, dural substitute reinforcement, and fibrin sealant application (Tisseel; Baxter International Inc., Deerfield, IL, USA), followed by rigid bone-flap fixation with titanium plates and screws. Beginning in September 2020, residual interosseous gaps were filled using PMMA bone cement prepared and applied according to the manufacturer’s instructions (commercially available PMMA cranial cement; manufacturer and location specified in the operative record), aiming to reinforce closure at this anatomical weak point (Fig. 3 ). Clinical variables and outcomes: The primary endpoint was the occurrence of postoperative CSF leak within 12 months. Secondary endpoints included wound complications, lumbar drain placement, ventriculoperitoneal shunt insertion, and hospital readmissions related to CSF leakage. Postoperative CSF leakage was defined as clinically evident incisional CSF drainage, radiologically confirmed pseudomeningocele requiring intervention, or CSF diversion procedure attributed to wound leakage within 12 months. Demographics (age, sex), comorbidities (hypertension, diabetes mellitus, immunosuppression), pathological diagnosis, craniotomy localization, laterality, incision type, hospital length of stay, and duration of follow-up were also recorded. All data were obtained retrospectively from the hospital’s electronic medical records system. Statistical analysis: Categorical variables were compared using chi-square or Fisher’s exact test as appropriate, while continuous variables were analyzed using Student’s t-test or Mann–Whitney U-test. Variables with clinical or univariate significance were entered into a multivariate logistic regression model to identify independent predictors of CSF leakage. Propensity score matching and additional risk estimates (absolute risk reduction and number needed to treat) were performed as sensitivity analyses to improve causal interpretability. A propensity score for receiving PMMA augmentation was estimated using a multivariable logistic regression model including clinically relevant covariates available preoperatively and intraoperatively (age, sex, comorbidities [hypertension, diabetes mellitus, immunosuppression], pathology category, craniotomy localization, laterality, incision type, and prior cranial surgery). Patients were matched 1:1 using nearest-neighbor matching without replacement with a caliper of 0.2 of the standard deviation of the logit of the propensity score. Covariate balance was assessed using standardized mean differences (SMD). SMD < 0.10 was considered ideal, although values < 0.20 were regarded as acceptable in sensitivity analyses. Matched-cohort outcome analysis: In the matched sample, the association between PMMA and CSF leak within 12 months was assessed using paired statistical tests (McNemar’s test for binary outcomes) and conditional logistic regression as appropriate, with effect sizes reported as odds ratios with 95% confidence intervals. Given the limited number of outcome events, PSM findings were interpreted as exploratory sensitivity analysis. Statistical significance was defined as p < 0.05. Analyses were performed using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY, USA). Results A total of 186 patients were included in this study (Fig. 2 ), of whom 135 (72.6%) underwent craniotomy with bone flap fixation using PMMA augmentation, while 51 (27.4%) underwent standard fixation without PMMA. The mean age was 54.2 years (range 18–78), and 90 (48.4%) were male and 96 (51.6%) were female. The mean length of hospital stay was 6.9 ± 17.2 days, and the mean follow-up was 576 ± 538 days with a minimum follow-up of 12 months in all patients. Baseline demographic, clinical, and surgical variables were comparable between the PMMA and No-PMMA groups without statistically significant imbalance across evaluated covariates (Table 1 ). Table 1 Univariate analysis of factors associated with CSF leak Variable CSF leak (%) p-value PMMA use No PMMA: 11.8 vs PMMA: 2.2 0.014* Sex Male: 3.3 vs Female: 6.2 0.499 Age (cut-off 54) < 54: 2.6 vs ≥ 54: 8.3 0.091 Hypertension Yes: 5.3 vs No: 4.7 1.000 Diabetes Yes: 6.1 vs No: 4.6 0.662 Smoking Yes: 4.5 vs No: 4.9 1.000 Immunosuppression Yes: 0.0 vs No: 5.2 1.000 Laterality Left: 9.3 vs Right: 1.0 0.013* Incision type Flap: 6.1 vs Linear: 3.8 0.511 Localization Frontal: 3.7, Temporal: 6.7, Parietal: 4.5, Occipital: 6.7 0.875 Pathology group See Table 3 0.147 Statistically significant predictors (p < 0.05) are marked in bold. Among the evaluated factors, only PMMA use has shown a significant protective effect against CSF leak. The following clinical and surgical characteristics were evaluated for their association with CSF leak, as summarized in Table 1 ; none of these factors were statistically significant, except for PMMA use. The right hemisphere was involved in 53.8% of procedures and the left hemisphere in 46.2%, with left-sided craniotomies showing higher leak rates on univariate analysis (9.3% vs 1.0%, p = 0.013), although this association did not remain significant in multivariate analysis (Table 2 ). Table 2 Multivariate logistic regression analysis of independent risk factors for CSF leak Variable Odds Ratio 95% Confidence Interval p-value PMMA use 0.17 0.03–0.92 0.039* Female sex 1.67 0.36–7.65 0.511 Age (continuous) 1.02 0.96–1.08 0.538 Hypertension 0.95 0.17–5.24 0.957 Diabetes 1.55 0.25–9.44 0.636 Laterality (Left) 2.41 0.58–10.07 0.227 Incision type 1.23 0.29–5.14 0.777 Localization Not significant – – Pathology group Not significant – – The model accounts for the overall variance in CSF leak risk. PMMA use has shown an independent protective effect (OR = 0.17, 95% CI: 0.03–0.92, p = 0.039), while no other variable has shown statistical significance. Pathology-specific CSF leak rates are summarized in Table 3 . No statistically significant difference was observed among pathology groups (p = 0.147), although aneurysm (22.2%) and hemangioma (50.0%) cases showed numerically higher leak proportions, likely reflecting very small subgroup sample sizes rather than a true pathological effect. Table 3 CSF leak rates by pathology Pathology n CSF leak n CSF leak % High-grade glioma 72 4 5.6 Meningioma 47 0 0.0 Metastasis 25 2 8.0 Aneurysm 9 2 22.2 AVM 8 0 0.0 Low-grade glioma 8 0 0.0 Colloid cyst 3 0 0.0 Cavernoma 3 0 0.0 Lymphoma 3 0 0.0 Dermoid cyst 2 0 0.0 Hemangioma 2 1 50.0 Arachnoid cyst 2 0 0.0 Abscess 1 0 0.0 Intracerebral hemorrhage 1 0 0.0 The analysis has shown no statistically significant differences across pathology groups (p = 0.147), although aneurysm and hemangioma cases have shown higher leak rates, limited by small sample sizes. During the first postoperative year, 9 patients (4.8%) developed a CSF leak (Table 4 ). The incidence of CSF leak was significantly lower in the PMMA group compared with the No PMMA group (2.2% vs 11.8%; p = 0.014), corresponding to an absolute risk reduction of 9.6% and a number-needed-to-treat of approximately 10 to prevent one postoperative leak. Lumbar drain placement was required in four patients (7.8%) in the No PMMA group but in none of the patients in the PMMA group, representing a statistically significant reduction with PMMA use (p = 0.005). Ventriculoperitoneal shunt insertion was performed in six patients (4.4%) in the PMMA group compared with four patients (7.8%) in the No PMMA group, not statistically significant (p = 0.466). During the follow-up period, readmissions due to CSF complications occurred in nine patients, predominantly among those without PMMA augmentation, and no complication directly attributable to PMMA was identified. Table 4 Characteristics of Patients with Postoperative CSF Leak (n = 9) P.N. PMMA Age Sex Comor. P.S. Loc Side Inc VPS LD Pathology 1 No 65 F HT, Car. No F Left Fl No No Metastasis 2 No 55 F HT No T Left Fl Yes Yes Aneurysm 3 No 70 F None No P Left Fl No Yes High-grade glioma 4 No 33 M None No F Left Lin No Yes Hemangioma 5 No 58 M Car. No O Left Lin No No Metastasis 6 No 54 M DM No F Left Lin No No High-grade glioma 7 Yes 43 M None Yes T Right Lin No No High-grade glioma 8 Yes 70 M HT, DM Yes P Left Fl No No High-grade glioma 9 Yes 56 M None No T Left Fl No No Aneurysm Case-level analysis has shown that most leaks occurred in patients without PMMA augmentation, with several requiring lumbar drainage or shunt procedures. Abbreviations: P.N. = patient number; Comor. = comorbidities; P.S. = prior surgery; Loc = localization; Side = side of craniotomy; Inc = incision type; VPS = ventriculoperitoneal shunt; LD = lumbar drain. Propensity score matching (PSM) sensitivity analysis: One-to-one nearest-neighbor matching without replacement (caliper 0.2 SD of the logit of the propensity score) yielded 38 matched pairs (n = 76). Covariate balance improved after matching (median standardized mean difference ≈ 0.13), although some residual imbalance persisted. In the matched cohort, CSF leakage occurred in 5/38 (13.2%) No-PMMA patients and 2/38 (5.3%) PMMA patients; the paired comparison (McNemar exact test) did not reach statistical significance (p = 0.45), while the direction of effect remained consistent with the primary analysis. Because propensity score matching excludes unmatched cases, the number of CSF leak events in the matched cohort differed from the total number observed in the full cohort. Risk Factor Analysis On univariate analysis, PMMA use was significantly protective (p = 0.014; Table 1 ), and left-sided craniotomies were associated with higher leak risk (p = 0.013). Age ≥ 54 years showed a non-significant trend toward higher leak rates (p = 0.091). Multivariate logistic regression confirmed PMMA use as an independent protective factor (OR = 0.17; 95% CI: 0.03–0.92; p = 0.039). Laterality and other covariates were not significant in the adjusted model. Case-level evaluation of the nine patients with postoperative CSF leakage demonstrated that the majority occurred in the absence of PMMA augmentation and that several required secondary CSF diversion procedures, further supporting the clinical relevance of PMMA-associated risk reduction (Table 4 ). Discussion One of the main concerns after cranial surgery is postoperative CSF leakage, which has been reported in 2.9% to 6.4% of craniotomy cases [ 7 ]. CSF leakage prolongs hospitalization, increases costs, and predisposes patients to serious complications such as wound infection and meningitis. Previous studies have shown that CSF leakage significantly increases the economic burden, with reports of additional costs of up to 15,000 USD per case and longer hospital stays, reflecting its impact on both patients and healthcare systems [ 3 , 6 , 13 ]. Meticulous watertight dural closure, the use of dural substitutes or sealants, and rigid bone flap fixation can reduce but not completely eliminate the problem [ 2 , 4 , 9 ]. Recent systematic evidence has further highlighted multiple surgical and anatomical determinants of postoperative CSF leakage following cranial procedures [ 12 ]. In our study, particular attention was directed to the residual gaps remaining at the bone edges after flap replacement during craniotomy closure. PMMA augmentation is a simple, inexpensive, and safe technique that can be easily integrated into routine surgical practice without adding morbidity [ 1 , 14 ]. By filling these residual gaps, the technique aims to reinforce cranial continuity and reduce pressure-driven CSF escape at the bone margin. Several studies have evaluated the role of cement cranioplasty in reducing CSF leaks after posterior fossa surgery. Ou et al. compared autologous bone flap fixation (n = 107) with PMMA cranioplasty (n = 136) following retrosigmoid craniectomy and demonstrated a significantly lower incidence of postoperative CSF leak (8.4% vs. 2.2%; p = 0.03) and pseudomeningocele (10.3% vs. 1.5%; p = 0.002) in the PMMA group, without increased wound infection or foreign body reaction [ 11 ]. Wolfson et al. reported long-term outcomes in 547 patients across 10 neurosurgeons, of whom 288 (52.7%) received cement cranioplasty and 259 (47.3%) did not. Cement use was associated with a significantly reduced CSF leak rate (4.5% vs. 14.3%; p < 0.001) and fewer cases of postoperative meningitis (0.7% vs. 5.2%; p = 0.003) [ 14 ]. In a recent meta-analysis of five retrospective studies including 1,838 patients, Benato et al. demonstrated that calcium phosphate cranioplasty significantly reduced the risk of pseudomeningocele (OR 0.26, 95% CI 0.15–0.46), wound CSF leaks (OR 0.11, 95% CI 0.03–0.40), and clinically relevant CSF leaks (OR 0.25, 95% CI 0.08–0.79). Furthermore, wound infections (OR 0.31, 95% CI 0.11–0.79) and reoperations (OR 0.19, 95% CI 0.05–0.71) were significantly less frequent in the cranioplasty group [ 3 ]. In a contemporary cohort of retrosigmoid craniotomies, Bauman et al. reported lower wound-specific complications (0% vs 10%; p = 0.002) and no pseudomeningocele with Calcium phosphate cement compared with 9% without Calcium phosphate cement (p = 0.006); craniotomy-site CSF leaks were 0 vs 6 cases, a non-significant difference likely limited by low event counts. Their accompanying meta-analysis (10 studies; n = 2166) showed reduced odds of wound CSF leak (OR 0.23, 95% CI 0.13–0.42) and infection (OR 0.17, 95% CI 0.08–0.38) with cement use [ 3 ]. Collectively, these studies suggest that cement-based cranial reconstruction techniques can decrease CSF-related complications, although the evidence has largely been limited to posterior fossa and skull-base procedures [ 10 ]. In our cohort of 186 patients, the overall leak rate was 4.8%, in line with published ranges. PMMA augmentation in supratentorial craniotomies was associated with a lower incidence of postoperative CSF leakage in the full cohort analysis, and multivariate modeling confirmed PMMA use as an independent protective factor. Secondary outcomes further supported the apparent safety profile of PMMA, with no increase in wound complications or shunt procedures and elimination of lumbar drain requirement in the PMMA group. No adverse event directly attributable to PMMA was identified. Sensitivity analysis using propensity score matching demonstrated a similar direction of effect, although statistical significance was not retained, likely reflecting reduced sample size and limited event numbers rather than absence of association. Taken together, these findings support a potential protective role of PMMA gap-filling augmentation in supratentorial craniotomy closure while highlighting the need for adequately powered prospective validation. Our findings align with prior reports in posterior fossa and skull base surgery, where cement-based cranioplasty or multilayer closure techniques reduced leak rates [ 3 , 5 , 10 , 11 , 14 ]. However, systematic evaluation specifically in supratentorial craniotomy has been limited, and the present series contributes additional clinical evidence in this setting. This study has limitations. Its retrospective design and single-center nature reduce generalizability, and the relatively small number of leak events limits statistical power. Residual confounding related to temporal practice changes cannot be fully excluded despite multivariate adjustment and propensity matching. Nevertheless, by focusing exclusively on supratentorial cases, our results provide hypothesis-generating evidence. Future prospective multicenter studies are warranted to validate the protective role of PMMA and clarify patient-selection criteria. Formal cost-effectiveness analyses would also be valuable. Conclusions PMMA gap-filling augmentation during supratentorial craniotomy closure was associated with a reduced rate of postoperative CSF leakage without evidence of increased morbidity in this retrospective cohort. These findings suggest a potential clinical benefit; however, prospective multicenter studies are required to confirm causality and define optimal indications. Declarations Compliance with Ethical standards: The study protocol was approved by the Institutional Ethics Committee of Ege University (approval no. 23-12.1T/46, dated 28 December 2023), and the study was conducted in accordance with the principles of the Declaration of Helsinki. Consent to participate: Written informed consent was obtained from each patient or, when not applicable, from their legal guardian. Competing interest: The authors declare no competing interests. Funding: The study did not receive any funding. Author Contribution H.B. and E.E.C. conceived and designed the study. performed data collection, data curation, and statistical analysis, and drafted the manuscript. B.B.A. and M.S.B. contributed to data collection and interpretation of the results and provided critical revisions of the manuscript. T.Y. provided overall supervision, contributed to interpretation of the findings, and critically revised the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript. Acknowledgement The authors thank all clinical staff involved in the care and follow-up of the patients included in this study. Data Availability The datasets generated and analyzed during the current study are not publicly available due to patient privacy and institutional restrictions but are available from the corresponding author on reasonable request and upon approval by the relevant institutional authorities. References Abd El-Ghani WMA (2018) Cranioplasty with polymethyl methacrylate implant: solutions of pitfalls. Egypt J Neurosurg 33:7 Barkhoudarian G, Garling RJ, Mallari RJ, Sivakumar W, Kelly DF (2024) A reliable closure technique for retromastoid craniotomy to avoid cerebrospinal fluid leaks and meningitis. Neurosurg Pract 5:e00086 Bauman MMJ, Webb KL, Michaelcheck CE et al (2025) Use of calcium phosphate bone cement in retrosigmoid craniotomies to reduce rates of pseudomeningocele and craniotomy-site cerebrospinal fluid leakage: a cohort study and meta-analysis. J Neurosurg 143:1027–1036 Bayatli E, Ozgural O, Erdin E et al (2025) Management of incisional cerebrospinal fluid leak in open cranial surgeries and the folding technique in duraplasty. Neurosurg Focus 58:E7 Benato A, Trevisi G, Palombi D, Zeoli F, Sturiale CL (2025) Impact of cement cranioplasty on cerebrospinal fluid leaks after retrosigmoid craniotomy: a systematic review and meta-analysis. J Clin Neurosci 135:111109 Chae JK, Rosen K, Zappi K et al (2024) Cranial and spinal cerebrospinal fluid leaks: foundations of identification and management. World Neurosurg 187:288–293 Coucke B, Van Gerven L, De Vleeschouwer S, Van Calenbergh F, van Loon J, Theys T (2022) The incidence of postoperative cerebrospinal fluid leakage after elective cranial surgery: a systematic review. Neurosurg Rev 45:1827–1845 Grotenhuis JA (2005) Costs of postoperative cerebrospinal fluid leakage: 1-year retrospective analysis of 412 consecutive nontrauma cases. Surg Neurol 64:490–494 Jankowitz BT, Atteberry DS, Gerszten PC et al (2009) Effect of fibrin glue on the prevention of persistent cerebral spinal fluid leakage after incidental durotomy during lumbar spinal surgery. Eur Spine J 18:1169–1174 Neill R, Harris P, Daggubati LC (2025) Bone cement versus bone flap replacement: a comparative meta-analysis of posterior fossa craniotomy complications. Surg Neurol Int 16:25 Ou C, Chen Y, Mo J et al (2019) Cranioplasty using polymethylmethacrylate cement following retrosigmoid craniectomy decreases the rate of cerebrospinal fluid leak and pseudomeningocele. J Craniofac Surg 30:566–570 Palermo M, Zeoli F, Rastegar V, Sturiale CL, Signorelli F (2025) Risk factors for postoperative cerebrospinal fluid fistulas after craniotomy and craniectomy: a systematic review and meta-analysis. Acta Neurochir. https://doi.org/10.1007/s00701-025-06685-3 van Lieshout C, Slot EMH, Kinaci A et al (2021) Cerebrospinal fluid leakage costs after craniotomy and health economic assessment of incidence reduction from a hospital perspective in the Netherlands. BMJ Open 11:e052553 Wolfson DI, Magarik JA, Godil SS et al (2021) Bone cement cranioplasty reduces cerebrospinal fluid leak rate after microvascular decompression: a single-institutional experience. J Neurol Surg B Skull Base 82:556–561 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8903756","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":594889705,"identity":"2fa886c2-697f-4369-83af-1b963f840db8","order_by":0,"name":"Hüseyin Biçeroğlu","email":"","orcid":"","institution":"Ege Üniversitesi Tıp Fakültesi Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Hüseyin","middleName":"","lastName":"Biçeroğlu","suffix":""},{"id":594889706,"identity":"433c7a83-008d-490b-a8e3-3a384c0f0abf","order_by":1,"name":"Elif Ezgi Çenberlitaş","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYJACZiCWYQOxPgAxGzuRWnjYgHoYZ4C0MBOrhQGohZkHxsUH+NkPH3tcUHGPh0+++fFnm1/b5PmYGRg/fMzBrUWyJy3deMaZYqDD2Mykc/tuG7YxMzBLztyGW4vBDR4zad62BJBfzJhze24zArWwMfPi0WJ/g/+bNO8/kBb2z58te27bE9RiIMHDJs3bANLCYyDN8ON2IkEtEmfSzKRnHANpySmT7G24ndzGzNiM1y/87YefSRfUJMjJNx/f/OHHn9u289ubD374iEcLKmBsA5MNxKoHgT+kKB4Fo2AUjIKRAgCa2ENGEQYc0wAAAABJRU5ErkJggg==","orcid":"","institution":"Ege Üniversitesi Tıp Fakültesi Hastanesi","correspondingAuthor":true,"prefix":"","firstName":"Elif","middleName":"Ezgi","lastName":"Çenberlitaş","suffix":""},{"id":594889707,"identity":"0dcc7c87-8574-4f86-b614-785599a9fd7f","order_by":2,"name":"Bilal Bahadır Akbulut","email":"","orcid":"","institution":"Bornova Türkan Özilhan State Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bilal","middleName":"Bahadır","lastName":"Akbulut","suffix":""},{"id":594889708,"identity":"753c6fae-5d10-497b-91e0-8ee82ea5a066","order_by":3,"name":"Mustafa Serdar Bölük","email":"","orcid":"","institution":"Ege Üniversitesi Tıp Fakültesi Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Mustafa","middleName":"Serdar","lastName":"Bölük","suffix":""},{"id":594889709,"identity":"fe23f85d-064e-495a-bbb8-194b795ad046","order_by":4,"name":"Taşkın Yurtseven","email":"","orcid":"","institution":"Ege Üniversitesi Tıp Fakültesi Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Taşkın","middleName":"","lastName":"Yurtseven","suffix":""}],"badges":[],"createdAt":"2026-02-17 18:53:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8903756/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8903756/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103510030,"identity":"02f85b89-c362-4f0e-b773-d59097f71fcf","added_by":"auto","created_at":"2026-02-26 14:03:00","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47916,"visible":true,"origin":"","legend":"\u003cp\u003eThree-dimensional reconstructed CT images demonstrating representative supratentorial craniotomy defects. (A) Large frontotemporoparietal cranial defect; red arrows indicate the margins of the bone defect. (B) Interosseous gaps filled using PMMA augmentation; the red arrow marks the reconstructed region. (C) Normal cranial anatomy without defect.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8903756/v1/fb029c7e1c04269544d0206a.jpeg"},{"id":103511474,"identity":"fba2695c-0bcf-4b1b-aa56-c596946119c9","added_by":"auto","created_at":"2026-02-26 14:09:53","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":64865,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart demonstrating patient inclusion and exclusion. After applying exclusion criteria, 186 patients met the eligibility criteria and were included in the final analysis.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8903756/v1/e6b6f51c99c2063c257e1d82.jpeg"},{"id":103514598,"identity":"696695d7-b52d-4b6f-a6e7-08bf40782d34","added_by":"auto","created_at":"2026-02-26 14:21:46","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":31392,"visible":true,"origin":"","legend":"\u003cp\u003eStep-by-step reconstruction of a craniotomy defect using PMMA. (A) Intraoperative view of the craniotomy site prior to reconstruction, showing the full extent of the bone defect before replacement of the bone flap. (B) The bone flap has been repositioned and secured with plates and screws; however, the PMMA augmentation has not yet been applied. White arrows indicate the residual cranial defect margins. (C) Final appearance following PMMA application and contouring. Yellow arrows demonstrate complete coverage of the previous defect and restoration of cranial continuity.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8903756/v1/1541754799090f9654666459.jpeg"},{"id":104781206,"identity":"438176a9-6850-435e-92ac-84f1df9c36b5","added_by":"auto","created_at":"2026-03-17 07:55:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":796729,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8903756/v1/5a8eda4d-e909-4319-9450-c353971649f6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Polymethyl Methacrylate Augmentation is Associated with Reduced Cerebrospinal Fluid Leak After Supratentorial Craniotomy: A Retrospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCerebrospinal fluid (CSF) leakage is one of the most frequent complications following cranial surgery [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], with reported rates ranging from 2.9% to 6.4% across all craniotomies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Such leaks are associated with prolonged hospitalization, increased healthcare costs, wound infections, and the risk of meningitis, thereby contributing substantially to postoperative morbidity [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Consequently, considerable efforts have been made to develop closure techniques that can minimize CSF leakage. Standard methods typically involve watertight dural closure, use of dural substitutes or sealants, and secure fixation of the bone flap with plates and screws [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite these measures, interosseous gaps between bone edges may still remain after flap fixation. These residual gaps can provide a potential pathway for CSF egress. Polymethyl methacrylate (PMMA) has long been used in neurosurgery for cranioplasty and skull reconstruction due to its biocompatibility, stability, and adaptability [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Its application to fill bone gaps at the time of craniotomy closure, however, has not been systematically evaluated. After approximating the dural edges with primary suturing, followed by duraplasty using Tisseel and an artificial dural substitute, the bone flap was fixed with plates and screws. The remaining interosseous gaps were then filled with PMMA to eliminate residual voids and reinforce the closure (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe present study aimed to assess whether PMMA augmentation reduces postoperative CSF leak rates compared with conventional craniotomy techniques. Secondary endpoints included wound complications, CSF diversion procedures, and hospital readmissions. Systematic evaluation in supratentorial craniotomy has been limited thus providing a novel contribution to the neurosurgical literature.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy design and patient selection: This retrospective cohort study included all consecutive adult patients who underwent supratentorial craniotomy performed by the same neurosurgical team at a university hospital between January 2018 and August 2024. Due to the transition to a new electronic medical record system in 2017, only patients operated on after January 2018 were included in this study. Only patients with a minimum follow-up of 12 months were included. The study period was truncated in August 2024 to ensure a minimum follow-up of 12 months for all included patients.\u003c/p\u003e \u003cp\u003eBoth primary and revision surgeries were included. Exclusion criteria were procedures involving the posterior fossa or cerebellum; however, occipital supratentorial cases were retained. The inclusion and exclusion process of the study cohort is summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on accumulating clinical experience and encouraging reports from the literature, our neurosurgical team at a university hospital introduced PMMA augmentation as a routine practice in September 2020. This provided a unique opportunity to compare outcomes before and after the adoption of PMMA augmentation within the same surgical practice.\u003c/p\u003e \u003cp\u003e Surgical technique and materials: All procedures were performed by the same neurosurgical team using a standardized closure protocol consisting of primary dural approximation, dural substitute reinforcement, and fibrin sealant application (Tisseel; Baxter International Inc., Deerfield, IL, USA), followed by rigid bone-flap fixation with titanium plates and screws. Beginning in September 2020, residual interosseous gaps were filled using PMMA bone cement prepared and applied according to the manufacturer\u0026rsquo;s instructions (commercially available PMMA cranial cement; manufacturer and location specified in the operative record), aiming to reinforce closure at this anatomical weak point (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eClinical variables and outcomes: The primary endpoint was the occurrence of postoperative CSF leak within 12 months. Secondary endpoints included wound complications, lumbar drain placement, ventriculoperitoneal shunt insertion, and hospital readmissions related to CSF leakage. Postoperative CSF leakage was defined as clinically evident incisional CSF drainage, radiologically confirmed pseudomeningocele requiring intervention, or CSF diversion procedure attributed to wound leakage within 12 months. Demographics (age, sex), comorbidities (hypertension, diabetes mellitus, immunosuppression), pathological diagnosis, craniotomy localization, laterality, incision type, hospital length of stay, and duration of follow-up were also recorded. All data were obtained retrospectively from the hospital\u0026rsquo;s electronic medical records system.\u003c/p\u003e \u003cp\u003eStatistical analysis: Categorical variables were compared using chi-square or Fisher\u0026rsquo;s exact test as appropriate, while continuous variables were analyzed using Student\u0026rsquo;s t-test or Mann\u0026ndash;Whitney U-test. Variables with clinical or univariate significance were entered into a multivariate logistic regression model to identify independent predictors of CSF leakage. Propensity score matching and additional risk estimates (absolute risk reduction and number needed to treat) were performed as sensitivity analyses to improve causal interpretability. A propensity score for receiving PMMA augmentation was estimated using a multivariable logistic regression model including clinically relevant covariates available preoperatively and intraoperatively (age, sex, comorbidities [hypertension, diabetes mellitus, immunosuppression], pathology category, craniotomy localization, laterality, incision type, and prior cranial surgery). Patients were matched 1:1 using nearest-neighbor matching without replacement with a caliper of 0.2 of the standard deviation of the logit of the propensity score. Covariate balance was assessed using standardized mean differences (SMD). SMD\u0026thinsp;\u0026lt;\u0026thinsp;0.10 was considered ideal, although values\u0026thinsp;\u0026lt;\u0026thinsp;0.20 were regarded as acceptable in sensitivity analyses. Matched-cohort outcome analysis: In the matched sample, the association between PMMA and CSF leak within 12 months was assessed using paired statistical tests (McNemar\u0026rsquo;s test for binary outcomes) and conditional logistic regression as appropriate, with effect sizes reported as odds ratios with 95% confidence intervals. Given the limited number of outcome events, PSM findings were interpreted as exploratory sensitivity analysis. Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were performed using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 186 patients were included in this study (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), of whom 135 (72.6%) underwent craniotomy with bone flap fixation using PMMA augmentation, while 51 (27.4%) underwent standard fixation without PMMA. The mean age was 54.2 years (range 18\u0026ndash;78), and 90 (48.4%) were male and 96 (51.6%) were female. The mean length of hospital stay was 6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2 days, and the mean follow-up was 576\u0026thinsp;\u0026plusmn;\u0026thinsp;538 days with a minimum follow-up of 12 months in all patients. Baseline demographic, clinical, and surgical variables were comparable between the PMMA and No-PMMA groups without statistically significant imbalance across evaluated covariates (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis of factors associated with CSF leak\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e Variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSF leak (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePMMA use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo PMMA: 11.8 vs PMMA: 2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.014*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale: 3.3 vs Female: 6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.499\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (cut-off 54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;54: 2.6 vs\u0026thinsp;\u0026ge;\u0026thinsp;54: 8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes: 5.3 vs No: 4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes: 6.1 vs No: 4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.662\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes: 4.5 vs No: 4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes: 0.0 vs No: 5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaterality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft: 9.3 vs Right: 1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.013*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncision type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlap: 6.1 vs Linear: 3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.511\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrontal: 3.7, Temporal: 6.7, Parietal: 4.5, Occipital: 6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.875\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSee Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eStatistically significant predictors (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) are marked in bold. Among the evaluated factors, only PMMA use has shown a significant protective effect against CSF leak.\u003c/p\u003e \u003cp\u003eThe following clinical and surgical characteristics were evaluated for their association with CSF leak, as summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e; none of these factors were statistically significant, except for PMMA use. The right hemisphere was involved in 53.8% of procedures and the left hemisphere in 46.2%, with left-sided craniotomies showing higher leak rates on univariate analysis (9.3% vs 1.0%, p\u0026thinsp;=\u0026thinsp;0.013), although this association did not remain significant in multivariate analysis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate logistic regression analysis of independent risk factors for CSF leak\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% Confidence Interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePMMA use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u0026ndash;0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.039*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.36\u0026ndash;7.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.511\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (continuous)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.96\u0026ndash;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.538\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17\u0026ndash;5.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.957\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25\u0026ndash;9.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.636\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaterality (Left)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.58\u0026ndash;10.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.227\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncision type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u0026ndash;5.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot significant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot significant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe model accounts for the overall variance in CSF leak risk. PMMA use has shown an independent protective effect (OR\u0026thinsp;=\u0026thinsp;0.17, 95% CI: 0.03\u0026ndash;0.92, p\u0026thinsp;=\u0026thinsp;0.039), while no other variable has shown statistical significance.\u003c/p\u003e \u003cp\u003ePathology-specific CSF leak rates are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. No statistically significant difference was observed among pathology groups (p\u0026thinsp;=\u0026thinsp;0.147), although aneurysm (22.2%) and hemangioma (50.0%) cases showed numerically higher leak proportions, likely reflecting very small subgroup sample sizes rather than a true pathological effect.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCSF leak rates by pathology\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCSF leak n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCSF leak %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-grade glioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeningioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAneurysm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAVM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow-grade glioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColloid cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCavernoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDermoid cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemangioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArachnoid cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntracerebral hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eThe analysis has shown no statistically significant differences across pathology groups (p\u0026thinsp;=\u0026thinsp;0.147), although aneurysm and hemangioma cases have shown higher leak rates, limited by small sample sizes.\u003c/span\u003e \u003c/p\u003e \u003cp\u003eDuring the first postoperative year, 9 patients (4.8%) developed a CSF leak (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The incidence of CSF leak was significantly lower in the PMMA group compared with the No PMMA group (2.2% vs 11.8%; p\u0026thinsp;=\u0026thinsp;0.014), corresponding to an absolute risk reduction of 9.6% and a number-needed-to-treat of approximately 10 to prevent one postoperative leak. Lumbar drain placement was required in four patients (7.8%) in the No PMMA group but in none of the patients in the PMMA group, representing a statistically significant reduction with PMMA use (p\u0026thinsp;=\u0026thinsp;0.005). Ventriculoperitoneal shunt insertion was performed in six patients (4.4%) in the PMMA group compared with four patients (7.8%) in the No PMMA group, not statistically significant (p\u0026thinsp;=\u0026thinsp;0.466). During the follow-up period, readmissions due to CSF complications occurred in nine patients, predominantly among those without PMMA augmentation, and no complication directly attributable to PMMA was identified.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of Patients with Postoperative CSF Leak (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP.N.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePMMA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eComor.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP.S.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLoc\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSide\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eInc\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eVPS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eLD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePathology\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHT, Car.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eMetastasis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eAneurysm\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh-grade glioma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHemangioma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCar.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eMetastasis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh-grade glioma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh-grade glioma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHT, DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh-grade glioma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eAneurysm\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCase-level analysis has shown that most leaks occurred in patients without PMMA augmentation, with several requiring lumbar drainage or shunt procedures. Abbreviations: P.N. = patient number; Comor. = comorbidities; P.S. = prior surgery; Loc\u0026thinsp;=\u0026thinsp;localization; Side\u0026thinsp;=\u0026thinsp;side of craniotomy; Inc\u0026thinsp;=\u0026thinsp;incision type; VPS\u0026thinsp;=\u0026thinsp;ventriculoperitoneal shunt; LD\u0026thinsp;=\u0026thinsp;lumbar drain.\u003c/p\u003e \u003cp\u003ePropensity score matching (PSM) sensitivity analysis: One-to-one nearest-neighbor matching without replacement (caliper 0.2 SD of the logit of the propensity score) yielded 38 matched pairs (n\u0026thinsp;=\u0026thinsp;76). Covariate balance improved after matching (median standardized mean difference\u0026thinsp;\u0026asymp;\u0026thinsp;0.13), although some residual imbalance persisted. In the matched cohort, CSF leakage occurred in 5/38 (13.2%) No-PMMA patients and 2/38 (5.3%) PMMA patients; the paired comparison (McNemar exact test) did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.45), while the direction of effect remained consistent with the primary analysis. Because propensity score matching excludes unmatched cases, the number of CSF leak events in the matched cohort differed from the total number observed in the full cohort.\u003c/p\u003e \u003cp\u003eRisk Factor Analysis\u003c/p\u003e \u003cp\u003eOn univariate analysis, PMMA use was significantly protective (p\u0026thinsp;=\u0026thinsp;0.014; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and left-sided craniotomies were associated with higher leak risk (p\u0026thinsp;=\u0026thinsp;0.013). Age\u0026thinsp;\u0026ge;\u0026thinsp;54 years showed a non-significant trend toward higher leak rates (p\u0026thinsp;=\u0026thinsp;0.091).\u003c/p\u003e \u003cp\u003eMultivariate logistic regression confirmed PMMA use as an independent protective factor (OR\u0026thinsp;=\u0026thinsp;0.17; 95% CI: 0.03\u0026ndash;0.92; p\u0026thinsp;=\u0026thinsp;0.039). Laterality and other covariates were not significant in the adjusted model.\u003c/p\u003e \u003cp\u003eCase-level evaluation of the nine patients with postoperative CSF leakage demonstrated that the majority occurred in the absence of PMMA augmentation and that several required secondary CSF diversion procedures, further supporting the clinical relevance of PMMA-associated risk reduction (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOne of the main concerns after cranial surgery is postoperative CSF leakage, which has been reported in 2.9% to 6.4% of craniotomy cases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. CSF leakage prolongs hospitalization, increases costs, and predisposes patients to serious complications such as wound infection and meningitis. Previous studies have shown that CSF leakage significantly increases the economic burden, with reports of additional costs of up to 15,000 USD per case and longer hospital stays, reflecting its impact on both patients and healthcare systems [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Meticulous watertight dural closure, the use of dural substitutes or sealants, and rigid bone flap fixation can reduce but not completely eliminate the problem [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Recent systematic evidence has further highlighted multiple surgical and anatomical determinants of postoperative CSF leakage following cranial procedures [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In our study, particular attention was directed to the residual gaps remaining at the bone edges after flap replacement during craniotomy closure. PMMA augmentation is a simple, inexpensive, and safe technique that can be easily integrated into routine surgical practice without adding morbidity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. By filling these residual gaps, the technique aims to reinforce cranial continuity and reduce pressure-driven CSF escape at the bone margin.\u003c/p\u003e \u003cp\u003eSeveral studies have evaluated the role of cement cranioplasty in reducing CSF leaks after posterior fossa surgery. Ou et al. compared autologous bone flap fixation (n\u0026thinsp;=\u0026thinsp;107) with PMMA cranioplasty (n\u0026thinsp;=\u0026thinsp;136) following retrosigmoid craniectomy and demonstrated a significantly lower incidence of postoperative CSF leak (8.4% vs. 2.2%; p\u0026thinsp;=\u0026thinsp;0.03) and pseudomeningocele (10.3% vs. 1.5%; p\u0026thinsp;=\u0026thinsp;0.002) in the PMMA group, without increased wound infection or foreign body reaction [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWolfson et al. reported long-term outcomes in 547 patients across 10 neurosurgeons, of whom 288 (52.7%) received cement cranioplasty and 259 (47.3%) did not. Cement use was associated with a significantly reduced CSF leak rate (4.5% vs. 14.3%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and fewer cases of postoperative meningitis (0.7% vs. 5.2%; p\u0026thinsp;=\u0026thinsp;0.003) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn a recent meta-analysis of five retrospective studies including 1,838 patients, Benato et al. demonstrated that calcium phosphate cranioplasty significantly reduced the risk of pseudomeningocele (OR 0.26, 95% CI 0.15\u0026ndash;0.46), wound CSF leaks (OR 0.11, 95% CI 0.03\u0026ndash;0.40), and clinically relevant CSF leaks (OR 0.25, 95% CI 0.08\u0026ndash;0.79). Furthermore, wound infections (OR 0.31, 95% CI 0.11\u0026ndash;0.79) and reoperations (OR 0.19, 95% CI 0.05\u0026ndash;0.71) were significantly less frequent in the cranioplasty group [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn a contemporary cohort of retrosigmoid craniotomies, Bauman et al. reported lower wound-specific complications (0% vs 10%; p\u0026thinsp;=\u0026thinsp;0.002) and no pseudomeningocele with Calcium phosphate cement compared with 9% without Calcium phosphate cement (p\u0026thinsp;=\u0026thinsp;0.006); craniotomy-site CSF leaks were 0 vs 6 cases, a non-significant difference likely limited by low event counts. Their accompanying meta-analysis (10 studies; n\u0026thinsp;=\u0026thinsp;2166) showed reduced odds of wound CSF leak (OR 0.23, 95% CI 0.13\u0026ndash;0.42) and infection (OR 0.17, 95% CI 0.08\u0026ndash;0.38) with cement use [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCollectively, these studies suggest that cement-based cranial reconstruction techniques can decrease CSF-related complications, although the evidence has largely been limited to posterior fossa and skull-base procedures [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our cohort of 186 patients, the overall leak rate was 4.8%, in line with published ranges. PMMA augmentation in supratentorial craniotomies was associated with a lower incidence of postoperative CSF leakage in the full cohort analysis, and multivariate modeling confirmed PMMA use as an independent protective factor. Secondary outcomes further supported the apparent safety profile of PMMA, with no increase in wound complications or shunt procedures and elimination of lumbar drain requirement in the PMMA group. No adverse event directly attributable to PMMA was identified.\u003c/p\u003e \u003cp\u003eSensitivity analysis using propensity score matching demonstrated a similar direction of effect, although statistical significance was not retained, likely reflecting reduced sample size and limited event numbers rather than absence of association. Taken together, these findings support a potential protective role of PMMA gap-filling augmentation in supratentorial craniotomy closure while highlighting the need for adequately powered prospective validation.\u003c/p\u003e \u003cp\u003eOur findings align with prior reports in posterior fossa and skull base surgery, where cement-based cranioplasty or multilayer closure techniques reduced leak rates [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, systematic evaluation specifically in supratentorial craniotomy has been limited, and the present series contributes additional clinical evidence in this setting.\u003c/p\u003e \u003cp\u003eThis study has limitations. Its retrospective design and single-center nature reduce generalizability, and the relatively small number of leak events limits statistical power. Residual confounding related to temporal practice changes cannot be fully excluded despite multivariate adjustment and propensity matching. Nevertheless, by focusing exclusively on supratentorial cases, our results provide hypothesis-generating evidence. Future prospective multicenter studies are warranted to validate the protective role of PMMA and clarify patient-selection criteria. Formal cost-effectiveness analyses would also be valuable.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePMMA gap-filling augmentation during supratentorial craniotomy closure was associated with a reduced rate of postoperative CSF leakage without evidence of increased morbidity in this retrospective cohort.\u003c/p\u003e \u003cp\u003eThese findings suggest a potential clinical benefit; however, prospective multicenter studies are required to confirm causality and define optimal indications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eCompliance with Ethical standards:\u003c/strong\u003e \u003cp\u003eThe study protocol was approved by the Institutional Ethics Committee of Ege University (approval no. 23-12.1T/46, dated 28 December 2023), and the study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to participate:\u003c/strong\u003e \u003cp\u003e Written informed consent was obtained from each patient or, when not applicable, from their legal guardian.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interest:\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThe study did not receive any funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eH.B. and E.E.C. conceived and designed the study. performed data collection, data curation, and statistical analysis, and drafted the manuscript. B.B.A. and M.S.B. contributed to data collection and interpretation of the results and provided critical revisions of the manuscript. T.Y. provided overall supervision, contributed to interpretation of the findings, and critically revised the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank all clinical staff involved in the care and follow-up of the patients included in this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to patient privacy and institutional restrictions but are available from the corresponding author on reasonable request and upon approval by the relevant institutional authorities.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAbd El-Ghani WMA (2018) Cranioplasty with polymethyl methacrylate implant: solutions of pitfalls. Egypt J Neurosurg 33:7\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarkhoudarian G, Garling RJ, Mallari RJ, Sivakumar W, Kelly DF (2024) A reliable closure technique for retromastoid craniotomy to avoid cerebrospinal fluid leaks and meningitis. Neurosurg Pract 5:e00086\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBauman MMJ, Webb KL, Michaelcheck CE et al (2025) Use of calcium phosphate bone cement in retrosigmoid craniotomies to reduce rates of pseudomeningocele and craniotomy-site cerebrospinal fluid leakage: a cohort study and meta-analysis. J Neurosurg 143:1027\u0026ndash;1036\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBayatli E, Ozgural O, Erdin E et al (2025) Management of incisional cerebrospinal fluid leak in open cranial surgeries and the folding technique in duraplasty. Neurosurg Focus 58:E7\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenato A, Trevisi G, Palombi D, Zeoli F, Sturiale CL (2025) Impact of cement cranioplasty on cerebrospinal fluid leaks after retrosigmoid craniotomy: a systematic review and meta-analysis. J Clin Neurosci 135:111109\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChae JK, Rosen K, Zappi K et al (2024) Cranial and spinal cerebrospinal fluid leaks: foundations of identification and management. World Neurosurg 187:288\u0026ndash;293\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoucke B, Van Gerven L, De Vleeschouwer S, Van Calenbergh F, van Loon J, Theys T (2022) The incidence of postoperative cerebrospinal fluid leakage after elective cranial surgery: a systematic review. Neurosurg Rev 45:1827\u0026ndash;1845\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrotenhuis JA (2005) Costs of postoperative cerebrospinal fluid leakage: 1-year retrospective analysis of 412 consecutive nontrauma cases. Surg Neurol 64:490\u0026ndash;494\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJankowitz BT, Atteberry DS, Gerszten PC et al (2009) Effect of fibrin glue on the prevention of persistent cerebral spinal fluid leakage after incidental durotomy during lumbar spinal surgery. Eur Spine J 18:1169\u0026ndash;1174\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeill R, Harris P, Daggubati LC (2025) Bone cement versus bone flap replacement: a comparative meta-analysis of posterior fossa craniotomy complications. Surg Neurol Int 16:25\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOu C, Chen Y, Mo J et al (2019) Cranioplasty using polymethylmethacrylate cement following retrosigmoid craniectomy decreases the rate of cerebrospinal fluid leak and pseudomeningocele. J Craniofac Surg 30:566\u0026ndash;570\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalermo M, Zeoli F, Rastegar V, Sturiale CL, Signorelli F (2025) Risk factors for postoperative cerebrospinal fluid fistulas after craniotomy and craniectomy: a systematic review and meta-analysis. Acta Neurochir. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00701-025-06685-3\u003c/span\u003e\u003cspan address=\"10.1007/s00701-025-06685-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Lieshout C, Slot EMH, Kinaci A et al (2021) Cerebrospinal fluid leakage costs after craniotomy and health economic assessment of incidence reduction from a hospital perspective in the Netherlands. BMJ Open 11:e052553\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWolfson DI, Magarik JA, Godil SS et al (2021) Bone cement cranioplasty reduces cerebrospinal fluid leak rate after microvascular decompression: a single-institutional experience. J Neurol Surg B Skull Base 82:556\u0026ndash;561\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"craniotomy, cerebrospinal fluid leak, polymethyl methacrylate, cranioplasty, postoperative complications","lastPublishedDoi":"10.21203/rs.3.rs-8903756/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8903756/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eCerebrospinal fluid leakage is a frequent complication following craniotomy, associated with morbidity, prolonged hospitalization, and increased healthcare costs. This study aimed to evaluate whether augmentation of craniotomy closure with polymethyl methacrylate reduces postoperative CSF leak rates compared to conventional closure techniques in supratentorial cases.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a retrospective, single‑center cohort study including consecutive adult patients who underwent supratentorial craniotomy between January 2018 and August 2024. Beginning in September 2020, PMMA augmentation was routinely applied to fill residual interosseous gaps after bone‑flap fixation, enabling a temporal cohort comparison. The primary endpoint was CSF leakage within 12 months. Multivariate logistic regression was used to identify independent predictors while accounting for potential confounders related to patient characteristics, pathology, and surgical variables.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 186 patients were analyzed (135 PMMA; 51 no PMMA). CSF leakage occurred in 9 patients (4.8%). Leakage was less frequent in the PMMA group (2.2% vs. 11.8%, p\u0026thinsp;=\u0026thinsp;0.014), corresponding to an absolute risk reduction of 9.6% and a number‑needed‑to‑treat of approximately 10. PMMA use remained independently associated with lower leak risk (OR 0.17, 95% CI 0.03\u0026ndash;0.92, p\u0026thinsp;=\u0026thinsp;0.039). No increase in wound complications, shunt procedures, or readmissions attributable to PMMA was observed.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePMMA augmentation during supratentorial craniotomy closure was associated with a reduced rate of postoperative CSF leakage without evidence of added morbidity. These findings suggest that gap‑filling augmentation may represent a useful adjunct in selected patients; however, prospective multicenter validation is warranted.\u003c/p\u003e","manuscriptTitle":"Polymethyl Methacrylate Augmentation is Associated with Reduced Cerebrospinal Fluid Leak After Supratentorial Craniotomy: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-25 08:55:07","doi":"10.21203/rs.3.rs-8903756/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8bb69000-f812-47f1-878f-928e9051e734","owner":[],"postedDate":"February 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-12T17:24:47+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-25 08:55:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8903756","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8903756","identity":"rs-8903756","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}