The Role of Fibrin Sealants in Endoscopic Repair of Cerebrospinal Fluid Rhinorrhea: A Comprehensive Review of Recurrence Rates

<p><b id="docs-internal-guid-7f33c3c4-7fff-a144-d4fb-8aa3f0756fbe" style="font-weight: normal;"><br /></b></p><h1 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 24pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The Role of Fibrin Sealants in Endoscopic Repair of Cerebrospinal Fluid Rhinorrhea: A Comprehensive Review of Recurrence Rates</span></h1><p><b style="font-weight: normal;"><br /><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">I. Executive Summary</span></h2><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">This report provides a comprehensive analysis of the use of fibrin sealants, such as Beriplast, in the surgical management of cerebrospinal fluid (CSF) rhinorrhea, with a specific focus on postoperative recurrence rates. A critical evaluation of the available clinical evidence, from observational studies to high-level systematic reviews and meta-analyses, indicates that while fibrin sealants are widely employed as a surgical adjunct, their use does not confer a statistically significant reduction in the long-term rate of CSF leak recurrence following endoscopic repair.</span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The primary determinants of a durable, successful repair are twofold. First is the meticulous surgical technique centered on a robust, multilayered structural reconstruction of the skull base defect. The choice of repair material—ranging from autologous free grafts for small defects to vascularized pedicled flaps for larger, more complex scenarios—is the foundational element of the procedure's success. Second, and of equal importance, is the identification and aggressive management of the underlying etiology, particularly elevated intracranial pressure (ICP), which is a principal driver of failure in spontaneous CSF leaks.</span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The role of fibrin sealants is best understood as that of a temporary bio-adhesive. They facilitate the initial placement and stabilization of grafts, particularly avascular free grafts, against CSF pulsations during the critical early healing phase. However, they do not contribute to the long-term biomechanical strength of the repair. Therefore, clinical focus and strategy should be directed toward optimizing the structural integrity of the reconstruction and mitigating the physiological forces that challenge it, rather than on the adjunctive use of a sealant.</span></p><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">II. Cerebrospinal Fluid Rhinorrhea: A Clinical Overview</span></h2><p><b style="font-weight: normal;"><br /><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Pathophysiology of CSF Leaks</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Cerebrospinal fluid rhinorrhea is a pathological condition defined by the leakage of CSF into the nasal and paranasal sinus cavities.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">1</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> It results from an anomalous communication between the subarachnoid space and the external aerodigestive tract, which occurs following a breach of the multiple layers separating the intracranial environment from the sinonasal mucosa: the dura mater, arachnoid membrane, and the bone of the skull base.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">2</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> CSF, produced primarily by the choroid plexus in the cerebral ventricles, circulates through the subarachnoid space before being reabsorbed into the venous system. A dural and osseous defect creates a pressure gradient that allows this fluid to escape, manifesting as clear nasal discharge.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">1</span></span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Etiological Classification and Clinical Significance</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The causes of CSF rhinorrhea are broadly classified as traumatic and non-traumatic. Historically, trauma is the leading overall cause, responsible for 80% to 90% of all cases.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">1</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Traumatic leaks are further subdivided into accidental (e.g., craniofacial fractures) and iatrogenic, with functional endoscopic sinus surgery (FESS) being a prominent iatrogenic cause. The lateral lamella of the cribriform plate is a site of particular vulnerability during FESS due to its thinness.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">1</span></span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">However, a critical distinction exists between the epidemiology of all CSF leaks and the etiology of leaks presenting for surgical repair. While trauma is the most common cause overall, a significant proportion of these leaks—approximately 70%—resolve spontaneously with conservative management, such as bed rest and observation.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">5</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> In contrast, non-traumatic or spontaneous leaks, which are often associated with underlying pathologies like idiopathic intracranial hypertension (IIH) or congenital skull base defects, are far less likely to resolve on their own and almost invariably require surgical intervention.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">7</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This phenomenon creates a "surgical filter," whereby patient cohorts in surgical studies are disproportionately composed of spontaneous leaks and traumatic leaks that have failed conservative measures. This explains why large surgical series frequently report spontaneous leaks as the most common etiology, with one major study finding them to account for 54.32% of surgically treated cases.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">3</span></span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The Imperative for Surgical Intervention: Preventing Meningitis</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The primary and most compelling reason for the surgical repair of a persistent CSF leak is the prevention of life-threatening ascending bacterial meningitis.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">1</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The direct communication between the non-sterile sinonasal cavity and the subarachnoid space creates a pathway for infection, with the reported risk of developing meningitis varying widely in untreated patients, from 5.6% to as high as 60%.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">3</span></span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The protective benefit of surgical intervention is profound and has been quantified by high-level evidence. A systematic review and meta-analysis of spontaneous lateral skull base CSF leaks calculated the pooled preoperative risk of meningitis to be 0.16 (a 16% incidence).</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">9</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Following surgical repair, the postoperative pooled risk fell dramatically to 0.01 (a 1% incidence). This represents a relative risk of 0.02, signifying a 98% reduction in the likelihood of developing meningitis after successful surgery.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">9</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This stark contrast underscores the high stakes of the procedure. A failed repair, or recurrence, re-exposes the patient to this significant risk, making the long-term durability of the closure a matter of paramount clinical importance.</span></p><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">III. The Modern Surgical Paradigm: Endoscopic Endonasal Repair</span></h2><p><b style="font-weight: normal;"><br /><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Evolution from Open Craniotomy</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The surgical management of CSF rhinorrhea has undergone a significant transformation over the past several decades. The traditional approach involved an open transcranial craniotomy, a major neurosurgical procedure requiring a large incision and retraction of the brain to access the skull base defect.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">1</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> While effective in many cases, this approach was associated with considerable morbidity, including the risk of anosmia (loss of smell), brain edema and contusion from retraction, hematoma, and seizures.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">10</span></span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The Endoscopic Approach as the Standard of Care</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The advent of the rigid endoscope has revolutionized the treatment of CSF rhinorrhea, establishing the endoscopic endonasal approach (EEA) as the current standard of care for the vast majority of leaks.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">5</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This minimally invasive technique, performed entirely through the nostrils, avoids external incisions and brain retraction, leading to lower morbidity and faster recovery times.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">3</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The efficacy of the EEA is well-established, with consistently high success rates reported across the literature. A large systematic review encompassing 1,778 fistula repairs found an overall success rate of 90% for primary repairs, rising to 97% for secondary (revision) repairs.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">15</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Numerous other series corroborate these findings, with success rates routinely exceeding 90%.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">5</span></span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Core Principles of the Endoscopic Technique</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The high success rate of the EEA is not merely a function of its less invasive nature. Rather, the technology of the endoscope enhances the surgeon's ability to apply fundamental surgical principles with greater precision.</span></p><ul style="margin-bottom: 0; margin-top: 0; padding-inline-start: 48px;"><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Precise Localization:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Accurate identification of the defect is the first critical step. This is achieved through a combination of preoperative high-resolution imaging, such as CT scans or CT/MR cisternography, and intraoperative visualization.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">6</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The use of intrathecal fluorescein, a dye injected into the CSF via a lumbar puncture, is a key technique. Under the endoscope's blue light filter, the fluorescein-tinged CSF glows a brilliant green-yellow, allowing for the direct and unambiguous localization of even very small or intermittent leaks.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">4</span></span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Defect Preparation:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Once identified, the mucosa surrounding the bony edges of the defect is carefully removed. This creates a raw, bleeding surface that promotes the integration and healing of the graft material that will be used for the repair.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">5</span></span></p></li></ul><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 12pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The endoscope's core advantages—superior illumination, high-magnification view, and the ability to use angled lenses to see around corners—directly facilitate these critical steps.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">3</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This enhanced visualization allows for more accurate localization, more complete preparation of the recipient site, and more precise placement of the reconstructive materials, which are the ultimate drivers of the high success rates associated with the modern endoscopic approach.</span></p><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">IV. A Multi-faceted Approach to Skull Base Reconstruction</span></h2><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The cornerstone of a durable CSF leak repair is the structural reconstruction of the skull base defect. Modern surgical practice employs a graduated approach, tailoring the reconstructive technique to the specific characteristics of the leak, primarily its size and flow rate.</span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The Foundational Role of Structural Grafts and Flaps</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The primary component of any repair is the biological material used to physically bridge the defect.</span></p><ul style="margin-bottom: 0; margin-top: 0; padding-inline-start: 48px;"><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Autologous Free Grafts:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> For small- to moderate-sized defects with low CSF flow, avascular free grafts harvested from the patient are commonly used. These include fascia lata (a thick, fibrous tissue from the thigh), adipose tissue (fat), and cartilage.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">20</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> These grafts rely on the blood supply from the prepared edges of the defect for their survival and integration.</span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Vascularized Pedicled Flaps:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> For large defects, high-flow leaks, or in revision surgery where the local tissue bed may be compromised, a vascularized flap is often the preferred choice. The pedicled nasoseptal flap (Hadad-Bassagasteguy flap) has become the workhorse for endoscopic skull base reconstruction.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">16</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This flap consists of mucosa and periosteum from the nasal septum, kept alive by its own dedicated blood supply from the posterior septal artery. This intrinsic vascularity makes it exceptionally robust and has been shown to improve success rates in challenging repairs.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">5</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> However, its reach can be limited, particularly for defects located high in the frontal sinus.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">5</span></span></p></li></ul><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The Principle of Multilayered Closure</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Regardless of the primary material used, modern reconstruction almost universally employs a multilayered technique to enhance the strength and seal of the repair.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">10</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This often involves a "sandwich" or "inlay-overlay" technique, where one layer of graft material (the inlay) is placed extradurally, between the dura and the bone, and a second layer (the overlay) is placed on the sinonasal side of the defect.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">22</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Evidence suggests that the number of layers correlates with success. One study found a statistically significant lower recurrence rate with 3- or 4-layered repairs compared to 2-layered repairs (8% and 25% vs. 50%, respectively; ).</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">23</span></span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The choice of reconstructive material is the primary strategic decision in CSF leak surgery, as summarized in Table 1.</span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Table 1: Comparison of Reconstruction Materials for CSF Rhinorrhea Repair</span></p><p><b style="font-weight: normal;"><br /></b></p><div align="left" dir="ltr" style="margin-left: 0pt;"><table style="border-collapse: collapse; border: none;"><colgroup><col width="125"></col><col width="125"></col><col width="125"></col><col width="125"></col><col width="125"></col></colgroup><tbody><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Material/Technique</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Primary Indications</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Advantages</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Disadvantages/Limitations</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Key References</span></p></td></tr><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Free Graft</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> (e.g., Fascia Lata, Fat, Mucosa)</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Small defects ( cm), low-flow leaks, primary repairs</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Readily available, low donor site morbidity, versatile</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Avascular, relies on surrounding tissue for healing, may be insufficient for high-pressure leaks</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">3</span></span></p></td></tr><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Vascularized Flap</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> (e.g., Nasoseptal Flap)</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Large defects ( cm), high-flow leaks, revision cases, post-radiation</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Robust vascular supply promotes healing, high success rate for complex defects</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Requires more extensive dissection, limited reach to certain areas (e.g., far-lateral frontal sinus), potential donor site morbidity</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">5</span></span></p></td></tr><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Rigid Reconstruction</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> (e.g., Bone, Cartilage)</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Defects requiring structural support, prevention of encephalocele formation, often used in combination with other grafts</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Provides a solid barrier, prevents herniation of brain tissue</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Can be more complex to place, potential for resorption over time</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">24</span></span></p></td></tr></tbody></table></div><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">V. Fibrin Sealants in Neurosurgery: Mechanism and Application</span></h2><p><b style="font-weight: normal;"><br /><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Biochemical Composition and Action</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Fibrin sealants, sold under brand names such as Beriplast and Tissucol, are two-component biological adhesives used widely in surgery.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">25</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The system is designed to mimic the final step of the physiological coagulation cascade.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">26</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The first component contains a concentrated solution of fibrinogen and Factor XIII, often with aprotinin to inhibit premature clot breakdown. The second component contains thrombin and calcium chloride. When mixed at the time of application, the thrombin rapidly converts the fibrinogen into fibrin monomers, which then polymerize and are cross-linked by Factor XIII to form a stable, solid fibrin clot within seconds.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">26</span></span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Intended Role as an Adjunctive Agent</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">In the context of skull base surgery, fibrin sealants are intended to serve three main functions: as a topical hemostatic agent to control minor bleeding, as a tissue adhesive to help secure grafts, and as a sealant to provide an immediate watertight closure.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">27</span></span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The biochemical nature and clinical application of these products define their role as a temporary adjunct to the healing process, not as a permanent component of the repair itself. The fibrin clot formed is a biological material that is eventually resorbed by the body's natural fibrinolytic processes. Its function is to act as a "primary seal (scab) until the biological implant [the graft] has the opportunity to mature and be integrated into a permanent scar that will serve as a long term seal".</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">27</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This means its primary purpose is to provide immediate, temporary adhesion, holding the main structural graft in position against the pulsatile forces of CSF and gravity during the critical initial days of healing. It is not designed to, nor can it, provide the long-term mechanical strength required to resist chronic physiological forces, a distinction fundamental to understanding its impact—or lack thereof—on long-term recurrence rates.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">28</span></span></p><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">VI. Evidence-Based Analysis of Recurrence Rates: Fibrin Sealant vs. No Sealant</span></h2><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">A hierarchical review of the clinical evidence is necessary to directly address the question of whether the use of fibrin sealants like Beriplast reduces the rate of CSF leak recurrence.</span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Highest-Level Evidence: Systematic Reviews and Meta-Analyses</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The most robust evidence comes from comprehensive reviews that aggregate data from multiple studies.</span></p><ul style="margin-bottom: 0; margin-top: 0; padding-inline-start: 48px;"><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">A 2016 systematic review analyzed 32 studies on the use of fibrin sealants in dura sealing.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">29</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> It included one randomized controlled trial (RCT), the highest level of evidence. This RCT found that while fibrin sealant significantly improved the rate of achieving an </span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: italic; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">intraoperative</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> watertight closure compared to sutures alone (92.1% vs. 38.0%), it was associated with a </span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: italic; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">higher</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">, though not statistically significant, rate of </span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: italic; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">postoperative</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> CSF leakage (6.7% in the sealant group vs. 2.0% in the control group).</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">29</span></span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">A more recent systematic review and meta-analysis from 2020 provides the most definitive conclusion to date.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">30</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> This study pooled data to directly compare outcomes. The analysis found that "Reconstruction with a tissue sealant did not significantly reduce postoperative CSF leak risk compared with reconstruction without sealant (Risk Difference [95% CI] = 0.02 [−0.01, 0.05])".</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">30</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Further sub-analyses of specific dural sealants and fibrin glues yielded similarly unremarkable results, showing no statistically significant benefit.</span></p></li></ul><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Observational Data and Older Studies</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Lower-level evidence from individual cohort studies and case series provides additional context.</span></p><ul style="margin-bottom: 0; margin-top: 0; padding-inline-start: 48px;"><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">A notable retrospective study from 1990 evaluated the use of Beriplast in 126 transsphenoidal surgeries.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">25</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> It reported a low postoperative rhinorrhea rate of 1.6%. The authors compared this to historical literature rates for repairs using autologous tissue alone (which ranged from 1.5% to 9.6%) and concluded that using fibrin glue "does not raise the incidence of postoperative rhinorrhea." This finding supports the safety (non-inferiority) of the sealant but does not demonstrate its superiority in preventing leaks.</span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">A very small 2012 case series from a developing country reported on five patients, four of whom had their repairs sealed with Beriplast.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">20</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> All five cases were successful. While encouraging, such a small, uncontrolled series cannot be used to draw generalizable conclusions about efficacy.</span></p></li></ul><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 12pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The apparent paradox from the RCT—that sealants can achieve a better immediate intraoperative seal yet fail to improve long-term postoperative outcomes—is resolved by understanding the different failure mechanisms. The immediate seal is a simple mechanical challenge that a rapid-acting glue can solve. However, postoperative recurrence is a failure of biological healing and the repair's ability to withstand chronic physiological stress. This failure can be due to graft migration, necrosis, or, most critically, mechanical disruption from persistent, unmanaged forces like elevated ICP. As the sealant is resorbed over days to weeks, it plays no role in the final biological integration of the graft or in buttressing the repair against these chronic forces. Therefore, the findings of the high-level reviews are not contradictory but are biologically and mechanically logical. The sealant solves a short-term problem (graft placement) but does not address the long-term challenges that are the true drivers of recurrence.</span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Table 2: Summary of Key Clinical Studies on Fibrin Sealant Efficacy and Recurrence Rates</span></p><p><b style="font-weight: normal;"><br /></b></p><div align="left" dir="ltr" style="margin-left: 0pt;"><table style="border-collapse: collapse; border: none;"><colgroup><col width="125"></col><col width="125"></col><col width="125"></col><col width="125"></col><col width="125"></col></colgroup><tbody><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Study (Identifier)</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Study Design</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Population/Intervention</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Key Finding on Recurrence</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Reported Recurrence Rates (Sealant vs. Control)</span></p></td></tr><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Ramakrishnan et al. 2020 </span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">30</span></span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Systematic Review & Meta-Analysis</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Endoscopic skull base surgery</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">No significant difference in postoperative CSF leak risk with sealant use.</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Risk Difference 0.02 (95% CI: -0.01 to 0.05)</span></p></td></tr><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Psaltis et al. 2016 </span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">29</span></span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Systematic Review (incl. 1 RCT)</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Dura sealing in neurosurgery</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Higher (non-significant) postoperative leak rate with sealant in the single RCT.</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">6.7% vs. 2.0% () in the RCT</span></p></td></tr><tr style="height: 0pt;"><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Shaffrey et al. 1990 </span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">25</span></span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Retrospective Cohort</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Transsphenoidal surgery</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Sealant use does not increase the leak rate compared to historical rates with autografts alone (non-inferiority).</span></p></td><td style="background-color: #f8fafd; border-bottom: solid #000000 0.75pt; border-left: solid #000000 0.75pt; border-right: solid #000000 0.75pt; border-top: solid #000000 0.75pt; overflow-wrap: break-word; overflow: hidden; padding: 6pt 9pt 6pt 9pt; vertical-align: top;"><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 6pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">1.6% vs. 1.5%-9.6% (historical control)</span></p></td></tr></tbody></table></div><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">VII. Critical Determinants of Surgical Success Beyond Sealant Use</span></h2><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The evidence strongly suggests that focusing on the use of an adjunctive sealant is a distraction from the factors that truly dictate long-term surgical outcomes. CSF leak recurrence is best understood as a failure of a biomechanical system, where success depends on achieving a state where the structural resistance of the repair exceeds the physiological load placed upon it.</span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">The "load" on the repair is primarily determined by the patient's intracranial pressure. This load is highest and most relentless in patients with untreated IIH, which is why spontaneous leaks are associated with the highest recurrence rates.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">7</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The "resistance" of the repair is determined by the quality of the structural reconstruction—the type of graft used (vascularized flaps are more robust), the number of layers applied (more layers are stronger), and the size of the defect it must span (larger defects are inherently weaker and are a predictor of recurrence).</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">23</span></span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Recurrence occurs when the load exceeds the resistance. A fibrin sealant is a negligible factor in this equation; it does not materially increase the long-term resistance of the repair, nor does it decrease the physiological load. Therefore, a successful, evidence-based surgical strategy must focus on maximizing resistance and minimizing load. This involves:</span></p><ul style="margin-bottom: 0; margin-top: 0; padding-inline-start: 48px;"><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Tailoring the Repair:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Using a robust, multilayered repair with a vascularized flap for large, high-flow defects, and an appropriate free graft for smaller defects.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">3</span></span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Managing ICP:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Aggressively diagnosing and treating elevated ICP in patients with spontaneous leaks through measures like weight loss, diuretics (e.g., acetazolamide), or, in refractory cases, CSF shunting procedures.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">1</span></span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: disc; margin-left: -12.75pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Considering Adjunctive Measures:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The use of perioperative lumbar drains is a common but controversial adjunct. While they can temporarily reduce the load on a repair, evidence suggests they significantly increase the length of hospital stay without necessarily reducing recurrence rates.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">17</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Their use is typically reserved for specific high-flow situations or to help manage ICP postoperatively.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">13</span></span></p></li></ul><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">VIII. Expert Consensus and Clinical Practice Guidelines</span></h2><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Professional societies, such as the American Rhinologic Society (ARS), provide guidance on best practices. The ARS has developed an expert practice statement (EPS) specifically on skull base reconstruction following endoscopic surgery, which explicitly addresses the roles of various materials, including dural sealants.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">32</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> While the abstracts of these guidelines do not detail the final specific recommendations, the focus of the documents and the broader consensus in the literature point away from sealants as a critical component.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">33</span></span></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">General patient information provided by the ARS emphasizes that the specifics of the repair, such as using a single layer versus multiple layers, depend on the size and location of the defect—a key determinant of success.</span><span style="background-color: transparent; color: #575b5f; font-family: 'Google Sans Text',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"><span style="font-size: 0.6em; vertical-align: super;">13</span></span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The document makes no mention of sealants as an essential element for a successful outcome. The lack of a strong, definitive recommendation </span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: italic; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">for</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> the routine use of fibrin sealants in major clinical guidelines, when combined with the high-level evidence showing no significant benefit, is itself a powerful indicator of their non-essential role in preventing recurrence. The consensus is that the focus should remain on the impactful variables: appropriate structural reconstruction and management of underlying pathology.</span></p><p><b style="font-weight: normal;"><br /></b></p><h2 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 18pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">IX. Conclusion and Clinical Recommendations</span></h2><p><b style="font-weight: normal;"><br /><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Definitive Synthesis of Evidence</span></h3><p><b style="font-weight: normal;"><br /></b></p><p dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 12pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Based on a critical appraisal of the available literature, with the greatest weight given to high-level systematic reviews and meta-analyses, the adjunctive use of Beriplast or other fibrin sealants does not result in a statistically significant reduction in the long-term recurrence rate of CSF rhinorrhea following endoscopic repair. While these agents may offer an intraoperative advantage in temporarily securing a graft, this benefit does not translate to improved long-term durability of the skull base closure.</span></p><p><b style="font-weight: normal;"><br /></b></p><h3 dir="ltr" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans',sans-serif; font-size: 13.999999999999998pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Evidence-Based Clinical Recommendations</span></h3><p><b style="font-weight: normal;"><br /></b></p><ol style="margin-bottom: 0; margin-top: 0; padding-inline-start: 48px;"><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -12pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Prioritize Structural Reconstruction:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> The foundation of a durable repair is a meticulous, multilayered closure using appropriate structural materials. The choice between an avascular free graft and a vascularized pedicled flap must be dictated by a careful assessment of the defect's size, location, CSF flow characteristics, and the patient's surgical history.</span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -12pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Identify and Manage Underlying Etiology:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> In all cases of spontaneous CSF rhinorrhea, a high index of suspicion for elevated ICP must be maintained and investigated. Failure to diagnose and effectively manage underlying conditions like IIH is a primary and preventable cause of surgical failure, irrespective of the reconstructive technique employed.</span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -12pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Contextualize the Role of Fibrin Sealants:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> Fibrin sealants should be viewed as an optional surgical adjunct, not an essential component for preventing recurrence. Their primary utility is as a temporary bio-adhesive to aid in the initial placement and stabilization of avascular free grafts. Their use remains a matter of surgeon preference and should not be relied upon to ensure the long-term success of the repair.</span></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -12pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.3799999713897704; margin-bottom: 6pt; margin-top: 0pt;"><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Future Research:</span><span style="background-color: transparent; color: #1b1c1d; font-family: 'Google Sans Text',sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;"> While current evidence is compelling, there remains a need for large, well-designed prospective randomized controlled trials to definitively confirm these findings and to explore whether sealants may have a niche role in specific, narrowly defined patient subgroups. However, based on the existing body of evidence, it is unlikely that such studies will alter the primary conclusion that structural integrity and pressure management are the true cornerstones of successful CSF rhinorrhea repair.</span></p></li></ol><h4 dir="ltr" style="line-height: 1.2; margin-bottom: 12.75pt; margin-top: 12.75pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Works cited</span></h4><p></p><ol style="margin-bottom: 0; margin-top: 0; padding-inline-start: 48px;"><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Contemporary Approach to the Diagnosis and Management of ..., accessed on October 12, 2025, </span><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4896656/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pmc.ncbi.nlm.nih.gov/articles/PMC4896656/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Cerebrospinal Fluid Leak - StatPearls - NCBI Bookshelf, accessed on October 12, 2025, </span><a href="https://www.ncbi.nlm.nih.gov/books/NBK538157/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://www.ncbi.nlm.nih.gov/books/NBK538157/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Analysis of Various Factors and Techniques to Improve Outcome of ..., accessed on October 12, 2025, </span><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6582018/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pmc.ncbi.nlm.nih.gov/articles/PMC6582018/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Endoscopic Endonasal Approach for Cerebrospinal Fluid Fistulae - Thieme Connect, accessed on October 12, 2025, </span><a href="https://www.thieme-connect.com/products/ejournals/html/10.1055/s-2006-932188?device=desktop&innerWidth=412&offsetWidth=412" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://www.thieme-connect.com/products/ejournals/html/10.1055/s-2006-932188?device=desktop&innerWidth=412&offsetWidth=412</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Clinical characteristics and surgical outcomes between traumatic ..., accessed on October 12, 2025, </span><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC12418327/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pmc.ncbi.nlm.nih.gov/articles/PMC12418327/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Diagnosis and Localization of Cerebrospinal Fluid Rhinorrhea: A Systematic Review - PMC, accessed on October 12, 2025, </span><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8972957/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pmc.ncbi.nlm.nih.gov/articles/PMC8972957/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Outcome of Endoscopic Cerebrospinal Fluid Rhinorrhoea Repair: An Institutional Study, accessed on October 12, 2025, </span><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6401007/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pmc.ncbi.nlm.nih.gov/articles/PMC6401007/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; 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list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">A Systematic Review and Meta-Analysis of Meningitis Risk Reduction After Repair of Spontaneous Lateral Skull Base Cerebrospinal Fluid Leaks - PubMed, accessed on October 12, 2025, </span><a href="https://pubmed.ncbi.nlm.nih.gov/41039648/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pubmed.ncbi.nlm.nih.gov/41039648/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Endoscopic Repair of Cerebrospinal Fluid (CSF) Rhinorrhea with Multilayer Grafts, accessed on October 12, 2025, </span><a href="https://www.researchgate.net/publication/352405098_Endoscopic_Repair_of_Cerebrospinal_Fluid_CSF_Rhinorrhea_with_Multilayer_Grafts" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://www.researchgate.net/publication/352405098_Endoscopic_Repair_of_Cerebrospinal_Fluid_CSF_Rhinorrhea_with_Multilayer_Grafts</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Outcome Comparison of Endoscopic (Endonasal Trans-Sphenoidal) Repairs of CSS Leak vs. Transcranial Approach, accessed on October 12, 2025, </span><a href="https://nja.pastic.gov.pk/PJNS/index.php/PJNS/article/download/813/807/807" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://nja.pastic.gov.pk/PJNS/index.php/PJNS/article/download/813/807/807</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Surgical Strategy for Cerebrospinal Fluid Rhinorrhea Repair - PubMed, accessed on October 12, 2025, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20489517/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pubmed.ncbi.nlm.nih.gov/20489517/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">CSF LEAKS REPAIR, accessed on October 12, 2025, </span><a href="https://nfsinus.com/wp-content/uploads/2025/06/CSF-Leak-Repair.pdf" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://nfsinus.com/wp-content/uploads/2025/06/CSF-Leak-Repair.pdf</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">CSF Leak Repair - Facial Plastic, Nasal, & Sinus Surgery - Drs. Goyal, accessed on October 12, 2025, </span><a href="https://sinuscenternj.com/csf-leak-repair/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://sinuscenternj.com/csf-leak-repair/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">A Systematic Review of the Endoscopic Repair of Cerebrospinal Fluid Leaks - PubMed, accessed on October 12, 2025, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22706995/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://pubmed.ncbi.nlm.nih.gov/22706995/</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Contemporary Management of Cerebrospinal Fluid Rhinorrhoea: A Review of the Literature, accessed on October 12, 2025, </span><a href="https://www.mdpi.com/2077-0383/14/3/995" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://www.mdpi.com/2077-0383/14/3/995</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Safety and Efficacy of Endoscopic Repair of CSF Leaks and Encephaloceles: A Survey of the Members of the American Rhinologic Society | Request PDF - ResearchGate, accessed on October 12, 2025, </span><a href="https://www.researchgate.net/publication/12073334_Safety_and_Efficacy_of_Endoscopic_Repair_of_CSF_Leaks_and_Encephaloceles_A_Survey_of_the_Members_of_the_American_Rhinologic_Society" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">https://www.researchgate.net/publication/12073334_Safety_and_Efficacy_of_Endoscopic_Repair_of_CSF_Leaks_and_Encephaloceles_A_Survey_of_the_Members_of_the_American_Rhinologic_Society</span></a></p></li><li aria-level="1" dir="ltr" style="background-color: transparent; color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; 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font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Surgical management of spontaneous middle cranial fossa defects ..., accessed on October 12, 2025, </span><a href="https://pubmed.ncbi.nlm.nih.gov/36703023/" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration-skip-ink: none; 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color: black; font-family: Arial,sans-serif; font-size: 11pt; font-style: normal; font-variant: normal; font-weight: 400; list-style-type: decimal; margin-left: -6pt; text-decoration: none; vertical-align: baseline; white-space: pre;"><p dir="ltr" role="presentation" style="line-height: 1.2; margin-bottom: 0pt; margin-top: 0pt;"><span style="background-color: transparent; color: black; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; vertical-align: baseline; white-space: pre-wrap; white-space: pre;">Fibrin Sealants in Dura Sealing: A Systematic Literature Review ..., accessed on October 12, 2025, </span><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151533" style="text-decoration: none;"><span style="-webkit-text-decoration-skip: none; background-color: transparent; color: #0000ee; font-family: 'Google Sans',sans-serif; font-size: 12pt; font-style: normal; font-variant: normal; 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The Role of Fibrin Sealants in Endoscopic Repair of Cerebrospinal Fluid Rhinorrhea: A Comprehensive Review of Recurrence Rates

The Role of Fibrin Sealants in Endoscopic Repair of Cerebrospinal Fluid Rhinorrhea: A Comprehensive Review of Recurrence Rates I. Executive ...

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